Patent application title:

Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of breast cancer

Publication number:

US20060183131A1

Publication date:
Application number:

11/043,842

Filed date:

2005-01-27

Abstract:

Novel markers for breast cancer that are both sensitive and accurate. These markers are overexpressed in breast cancer specifically, as opposed to normal breast tissue. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between breast cancer and non-cancerous states.

Inventors:

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Classification:

G01N33/57415 »  CPC main

Investigating or analysing materials by specific methods not covered by groups -; Biological material, e.g. blood, urine ; Haemocytometers; Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing; Immunoassay; Biospecific binding assay; Materials therefor for cancer; Specifically defined cancers of breast

C07K14/47 »  CPC further

Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

C12Q1/6886 »  CPC further

Measuring or testing processes involving enzymes, nucleic acids or microorganisms ; Compositions therefor; Processes of preparing such compositions involving nucleic acids; Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

C12Q2600/112 »  CPC further

Oligonucleotides characterized by their use Disease subtyping, staging or classification

C12Q2600/158 »  CPC further

Oligonucleotides characterized by their use Expression markers

C12Q1/68 IPC

Measuring or testing processes involving enzymes, nucleic acids or microorganisms ; Compositions therefor; Processes of preparing such compositions involving nucleic acids

G01N33/574 IPC

Investigating or analysing materials by specific methods not covered by groups -; Biological material, e.g. blood, urine ; Haemocytometers; Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing; Immunoassay; Biospecific binding assay; Materials therefor for cancer

C07H21/04 IPC

Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical

C12P21/06 IPC

Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products

C07K14/82 IPC

Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof Translation products from oncogenes

C07K16/30 IPC

Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)

THIS APPLICATION IS RELATED TO NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS OF BREAST CANCER, AND CLAIMS PRIORITY TO THE BELOW U.S. PROVISIONAL APPLICATIONS WHICH ARE INCORPORATED BY REFERENCE HEREIN:

APPLICATION NO. 60/620,916 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN COLON CANCER

APPLICATION NO. 60/628,123 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN COLON CANCER II

APPLICATION NO. 60/621,131 FILED OCT. 25, 2004—DIAGNOSTIC MARKERS FOR COLON CANCER, AND ASSAYS AND METHODS OF USE THEREOF

APPLICATION NO. 60/620,917 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN BREAST CANCER

APPLICATION NO. 60/628,101 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN BREAST CANCER II

APPLICATION NO. 60/620,874 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN OVARIAN CANCER

APPLICATION NO. 60/628,134 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN OVARIAN CANCER II

APPLICATION NO. 60/620,924 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN STOMACH CANCER

APPLICATION NO. 60/628,111 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN STOMACH CANCER II

APPLICATION NO. 60/620,853 FILED OCT. 22, 2004-28814—DIFFERENTIAL EXPRESSION OF MARKERS IN LUNG CANCER

APPLICATION NO. 60/628,112 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN LUNG CANCER II

APPLICATION NO. 60/620,974 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN PANCREATIC CANCER

APPLICATION NO. 60/628,145 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN PANCREATIC CANCER II

APPLICATION NO. 60/620,656 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN PROSTATE CANCER

APPLICATION NO. 60/628,251 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN PROSTATE CANCER II

APPLICATION NO. 60/620,975 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN BRAIN CANCER

APPLICATION NO. 60/628,178 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN BRAIN CANCER II

APPLICATION NO. 60/628,231 FILED NOV. 17, 2004—NOVEL DIAGNOSTIC SERUM MARKERS, AND ASSAYS AND METHODS OF USE THEREOF

APPLICATION NO. 60/620,918 FILED OCT. 22, 2004—DIAGNOSTIC MARKERS FOR RENAL CANCER, AND ASSAYS AND METHODS OF USE THEREOF

APPLICATION NO. 60/628,156 FILED NOV. 17, 2004—DIAGNOSTIC MARKERS FOR RENAL CANCER, AND ASSAYS AND METHODS OF USE THEREOF II

APPLICATION NO. 60/628,167 FILED NOV. 17, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN BLADDER CANCER II

APPLICATION NO. 60/621,004 FILED OCT. 22, 2004—DIFFERENTIAL EXPRESSION OF MARKERS IN SKIN AND EPITHELIAL CANCER II

APPLICATION NO. ----NA----- FILED NOV. 17, 2004—NOVEL DIAGNOSTIC MARKERS, AND ASSAYS AND METHODS OF USE THEREOF

APPLICATION NO. 60/539,129 FILED JAN. 27, 2004—METHODS AND SYSTEMS FOR ANNOTATING BIOMOLECULAR SEQUENCES

APPLICATION NO. 60/539,128 FILED JAN. 27, 2004—EVOLUTIONARY CONSERVED SPLICED SEQUENCES AND METHODS AND SYSTEMS FOR IDENTIFYING THEREOF

FIELD OF THE INVENTION

The present invention is related to novel nucleotide and protein sequences that are diagnostic markers for breast cancer, and assays and methods of use thereof.

BACKGROUND OF THE INVENTION

Breast cancer is the most commonly occurring cancer in women, comprising almost a third of all malignancies in females. It is the leading cause of death for women between the ages 40-55 in the United States and one out of 8 females in the United States will develop breast cancer at some point in her life.

The death rate from breast cancer has been slowly declining over the past decade, partially due do the usage of molecular markers that facilitate the discovery, tumor typing (and therefore choice of treatment), response to treatment and recurrence.

The most widely used serum markers for breast cancers are Mucin1 (measured as CA 15-3) and CEA (CarcinoEmbryonic Antigen). Mucin 1 (MUC1) is present on the apical surface of normal epithelial cells. Its extracellular domain consists of a heavily O-linked glycosylated peptide core made up of variable number of multiple repeats of 20 amino acid sequence referred to as VNTR (Variable Number Tandem Repeat). This variability results in natural polymorphism of MUC1. Each VNTR has five potential O-linkage sites. The breast cancer disease state alters the enzymes which glycosylate Mucin 1 and therefore the polysaccharide side chains of tumor associated MUC1 are generally shorter than those on the normally expressed molecule. Both aberrant and up-regulated expression of MUC1 are features of malignancy and MUC1 related markers are based on it. Though CA 15-3 is a broadly used marker for breast cancer, a combination of CA 15-3 and CEA is more sensitive than using a single marker.

For the purpose of monitoring therapeutic response, CA 15-3, CEA and ESR (Erythrocyte Sedimentation Rate) are used as a panel, leading to over 90% of patients biochemically assessable. Serum markers used to monitor therapeutic response in patients with metastatic breast cancer are associated with the “spike phenomenon”. It is an initial transient rise of tumor marker levels which can be seen in up to 30% of responders in the first 3 months of commencing a therapy. It is important not to interpret this as a sign of disease progression leading to premature change of an effective therapy.

CA 27.29 is a new monoclonal antibody directed against a different part of MUC1 and it is a newer marker than CA 15-3. It detects a different glycosylation pattern of MUC1, as compared with CA 15-3. CA 27.29 is the first FDA-approved blood test for breast cancer recurrence. Because of superior sensitivity and specificity, CA 27.29 has supplanted CA 15-3 as the preferred tumor marker in breast cancer. The CA 27.29 level is elevated in approximately one third of women with early-stage breast cancer (stage I or II) and in two thirds of women with late-stage disease (stage III or IV). CA 27.29 lacks predictive value in the earliest stages of breast cancer and thus has no role in screening for or diagnosing the malignancy. CA 27.29 also can be found in patients with benign disorders of the breast, liver, and kidney, and in patients with ovarian cysts. However, CA 27.29 levels higher than 100 units per mL are rare in benign conditions.

Recently Estrogen 2 (beta) was shown to have a diagnostic role in breast cancer. It has been shown that the expression of the ‘cx’ variant of Estrogen 2 is correlated with response to Hormone adjuvant therapy. In addition it has been shown it may assist in better characterization of ER-1 positive breast cancers (together with progesterone receptor).

HER-2 (also known as c-erbB2) is a membrane proto-oncogene with intrinsic tyrosine kinase activity. Tumor expressing HER-2 are associated with shorter survival, shorter time-to-relapse and an overall worse prognosis. Tumors expressing HER-2 can be targeted with Trastuzumab—a biological adjuvant therapy which blocks the growth promoting action of HER-2. The ImmunoHistoChemistry (IHC) and Fluorescence In Situ Hybridization (FISH) tests are used to detect HER2: 1.IHC: The most common test used to check HER2 status is an ImmunoHistoChemistry (IHC) test. The IHC test measures the protein made by the HER2 gene. 2.FISH: This test measures the number of copies of the HER2 gene present in the tumor cell.

Measurement of the extracellular domain of HER-2 has been reported to show a better assessment of response to chemotherapy than a biochemical index score based on measurement of CA 15.3, CEA and ESR in a small series of patient. That finding is yet to be confirmed in a larger group of patient with HER-2 expressing tumors.

Other molecular markers, mainly used for the diagnosis for cancers other than breast cancer were shown to have a diagnostic potential in breast cancer. For example, CA125 which is a major marker for ovarian cancer is also associated with breast cancer. High levels of CA 19-9, a major marker for colorectal and pancreatic cancers, can be found in breast cancer. Overall, these markers are not frequently used for the detection of breast cancer to due their inferiority compared with other markers already described.

Panels of markers for the diagnosis and typing of breast cancer are being used by pathologists, including both markers described above and additional markers, such as immunohistochemistry markers that have been shown to have a beneficial value for the diagnosis of breast cancer, including PCNA and Ki-67 are maybe the most important and highly used immunohistochemistry markers for breast cancer. Other markers as E-Cadherin, Cathepsin D and TFF1 are also used for that purpose.

Despite relevant research efforts and the identification of many putative good prognosticators, few of them are proving clinically useful for identifying patients at minimal risk of relapse, patients with a worse prognosis, or patients likely to benefit from specific treatments. Most of them, such as epidermal growth factor receptor, cyclin E, p53 (this mutation is present in approximately 40% of human breast cancers as an acquired defect), bcl-2, vascular endothelial growth factor, urokinase-type plasminogen activator-1 and the anti-apoptosis protein survivin, are suggested for possible inclusion in the category of biomarkers with a high level of clinico-laboratory effectiveness. However, no single biomarker was able to identify those patients with the best (or worst) prognosis or those patients who would be responsive to a given therapy. High level cyclin E expression has been associated with the initiation or progression of different human cancers, in particular breast cancer but also leukemia, lymphoma and others. Cyclin-E expression level in the breast cancer was found to be a very strong indicator for prognosis, stronger than any other biological marker.

There are some non-cancerous pathological conditions which represent an increased risk factor for development breast cancer. Non-limiting examples of these conditions include:

    • Ductal hyperplasia without atypia. It is the most frequently encountered breast biopsy result that is associated with increased risk of future development of breast cancer (2 fold increased risk). In particular, the loss of expression of transforming growth factor beta receptor II in the affected epithelial cells is associated with an increased risk of invasive breast cancer.
    • Atypical hyperplasia. Women having atypical hyperplasia with over-expression of HER-2 have a greater than 7-fold increased risk of developing invasive breast carcinoma, as compared with women with non-proliferative benign breast lesions and no evidence of HER-2 amplification.

These pathological conditions should be effectively diagnosed and monitored in order to facilitate early detection of breast cancer.

SUMMARY OF THE INVENTION

The background art does not teach or suggest markers for breast cancer that are sufficiently sensitive and/or accurate, alone or in combination.

The present invention overcomes these deficiencies of the background art by providing novel markers for breast cancer that are both sensitive and accurate. These markers are overexpressed in breast cancer specifically, as opposed to normal breast tissue. The measurement of these markers, alone or in combination, in patient (biological) samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between breast cancer and non-cancerous states.

According to preferred embodiments of the present invention, examples of suitable biological samples which may optionally be used with preferred embodiments of the present invention include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, breast tissue, any human organ or tissue, including any tumor or normal tissue, any sample obtained by lavage (for example of the bronchial system or of the breast ductal system), and also samples of in vivo cell culture constituents. In a preferred embodiment, the biological sample comprises breast tissue and/or a serum sample and/or a urine sample and/or a milk sample and/or any other tissue or liquid sample. The sample can optionally be diluted with a suitable eluant before contacting the sample to an antibody and/or performing any other diagnostic assay.

Information given in the text with regard to cellular localization was determined according to four different software programs: (i) tmhmm (from Center for Biological Sequence Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/TMHMM/TMHMM2.0b.guide.php) or (ii) tmpred (from EMBnet, maintained by the ISREC Bionformatics group and the LICR Information Technology Office, Ludwig Institute for Cancer Research, Swiss Institute of Bioinformatics, http://www.ch.embnet.org/software/TMPRED_form.html) for transmembrane region prediction; (iii) signalp_hmm or (iv) signalp_nn (both from Center for Biological Sequence Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/SignalP/background/prediction.php) for signal peptide prediction. The terms “signalp_hmm” and “signalp_nn” refer to two modes of operation for the program SignalP: hmm refers to Hidden Markov Model, while nn refers to neural networks. Localization was also determined through manual inspection of known protein localization and/or gene structure, and the use of heuristics by the individual inventor. In some cases for the manual inspection of cellular localization prediction inventors used the ProLoc computational platform [Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004) “Evolution of multicellularity in metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis.” Cell Biology International 2004;28(3):171-8.], which predicts protein localization based on various parameters including, protein domains (e.g., prediction of trans-membranous regions and localization thereof within the protein), pI, protein length, amino acid composition, homology to pre-annotated proteins, recognition of sequence patterns which direct the protein to a certain organelle (such as, nuclear localization signal, NLS, mitochondria localization signal), signal peptide and anchor modeling and using unique domains from Pfam that are specific to a single compartment.

Information is given in the text with regard to SNPs (single nucleotide polymorphisms). A description of the abbreviations is as follows. “T→C”, for example, means that the SNP results in a change at the position given in the table from T to C. Similarly, “M→Q”, for example, means that the SNP has caused a change in the corresponding amino acid sequence, from methionine (M) to glutamine (Q). If, in place of a letter at the right hand side for the nucleotide sequence SNP, there is a space, it indicates that a frameshift has occurred. A frameshift may also be indicated with a hyphen (-). A stop codon is indicated with an asterisk at the right hand side (*). As part of the description of an SNP, a comment may be found in parentheses after the above description of the SNP itself. This comment may include an FTId, which is an identifier to a SwissProt entry that was created with the indicated SNP. An FTId is a unique and stable feature identifier, which allows construction of links directly from position-specific annotation in the feature table to specialized protein-related databases. The FTId is always the last component of a feature in the description field, as follows: FTId=XXX_number, in which XXX is the 3-letter code for the specific feature key, separated by an underscore from a 6-digit number. In the table of the amino acid mutations of the wild type proteins of the selected splice variants of the invention, the header of the first column is “SNP position(s) on amino acid sequence”, representing a position of a known mutation on amino acid sequence. SNPs may optionally be used as diagnostic markers according to the present invention, alone or in combination with one or more other SNPs and/or any other diagnostic marker. Preferred embodiments of the present invention comprise such SNPs, including but not limited to novel SNPs on the known (WT or wild type) protein sequences given below, as well as novel nucleic acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a variant amino acid and/or nucleic acid sequence described herein.

Information given in the text with regard to the Homology to the known proteins was determined by Smith-Waterman version 5.1.2 using special (non default) parameters as follows:

model=sw.model
GAPEXT=0
GAPOP=100.0
 MATRIX=blosum100

Information is given with regard to overexpression of a cluster in cancer based on ESTs. A key to the p values with regard to the analysis of such overexpression is as follows:

    • library-based statistics: P-value without including the level of expression in cell-lines (P1)
    • library based statistics: P-value including the level of expression in cell-lines (P2)
    • EST clone statistics: P-value without including the level of expression in cell-lines (SP1)
    • EST clone statistics: predicted overexpression ratio without including the level of expression in cell-lines (R3)
    • EST clone statistics: P-value including the level of expression in cell-lines (SP2)
    • EST clone statistics: predicted overexpression ratio including the level of expression in cell-lines (R4)

Library-based statistics refer to statistics over an entire library, while EST clone statistics refer to expression only for ESTs from a particular tissue or cancer.

Information is given with regard to overexpression of a cluster in cancer based on microarrays. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. There are two types of microarray results: those from microarrays prepared according to a design by the present inventors, for which the microarray fabrication procedure is described in detail in Materials and Experimental Procedures section herein; and those results from microarrays using Affymetrix technology. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. For microarrays prepared according to a design by the present inventors, the probe name begins with the name of the cluster (gene), followed by an identifying number. Oligonucleotide microarray results taken from Affymetrix data were from chips available from Affymetrix Inc, Santa Clara, Calif., USA (see for example data regarding the Human Genome U133 (HG-U133) Set at www.affymetrix.com/products/arrays/specific/hgu133..affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133av2.affx; and Human Genome U133 Plus 2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133plus.affx). The probe names follow the Affymetrix naming convention. The data is available from NCBI Gene Expression Omnibus (see www.ncbi.nlm.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1207-210). The dataset (including results) is available from www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1133 for the Series GSE1133 database (published on March 2004); a reference to these results is as follows: Su et al (Proc Natl Acad Sci USA. Apr. 20, 2004;101(16):6062-7. Epub Apr. 09, 2004). The probes designed according to the present inventors are listed below.

>Z21368_0_0_61857
AGTTCATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACTCTTGAAG (SEQ ID NO:895)
>HUMGRP5E_0_0_16630
GCTGATATGGAAGTTGGGGAATCTGAATTGCCAGAGAATCTTGGGAAGAG (SEQ ID NO:896)
>HUMGRP5E_0_2_0
TCTCATAGAAGCAAAGGAGAACAGAAACCACCAGCCACCTCAACCCAAGG (SEQ ID NO:897)
>HSENA78_0_1_0
TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC (SEQ ID NO:898)
>M85491_0_0_25999
GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC (SEQ ID NO:899)
>M85491_0_14_0
GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG (SEQ ID NO:900)
>HSSTROL3_0_0_12518
ATGAGAGTAACCTCACCCGTGCACTAGTTTACAGAGCATTCACTGCCCCA (SEQ ID NO:901)
>HSSTROL3_0_0_12517
CAGAGATGAGAGCCTGGAGCATTGCAGATGCCAGGGACTTCACAAATGAA (SEQ ID NO:902)
>HUMCA1XIA_0_0_14909
GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG (SEQ ID NO:903)
>HUMCA1XIA_0_18_0
TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG (SEQ ID NO:904)
>R20779_0_0_30670
CCGCGTTGCTTCTAGAGGCTGAATGCCTTTCAAATGGAGAAGGCTTCCAT (SEQ ID NO:905)
>HSS100PCB_0_0_12280
CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGCTCTAAAA (SEQ ID NO:906)
>HSCOC4_0_0_9892
AAGGACCAGAGTCCATGCCAAGACCACCCTTCAGCTTCCAAGGCCCTCCA (SEQ ID NO:907)
>HSCOC4_0_39_0
ATCCTCCAGCCATGAGGCTGCTCTGGGGGCTGATCTGGGCATCCAGCTTC (SEQ ID NO:908)
>HSCOC4_0_0_9883
CCTGTTTGCTCTGACACCAACTTCCTACCCTCTCAGCCTCAAAGTAACTC (SEQ ID NO:909)
>HSCOC4_0_0_9885
GCTGAGGTGTGGCCGAGGACCTGACCATCTGGAAGTGTGAAAATCCCCTT (SEQ ID NO:910)
>T11628_0_9_0
ACAAGATCCCCGTGAAGTACCTGGAGTTCATCTCGGAATGCATCATCCAG (SEQ ID NO:911)
>T11628_0_0_45174
TAAACAATCAAAGAGCATGTTGGCCTGGTCCTTTGCTAGGTACTGTAGAG (SEQ ID NO:912)
>T11628_0_0_45161
TGCCTCGCCACAATGGCACCTGCCCTAAAATAGCTTCCCATGTGAGGGCT (SEQ ID NO:913)
>M78076_0_7_0
GAGAAGATGAACCCGCTGGAACAGTATGAGCGAAAGGTGAATGCGTCTGT (SEQ ID NO:914)
>HSMUC1A_0_37_0
AAAAGGAGACTTCGGCTACCCAGAGAAGTTCAGTGCCCAGCTCTACTGAG (SEQ ID NO:915)
>HSMUC1A_0_0_11364
AAAGGCTGGCATAGGGGGAGGTTTCCCAGGTAGAAGAAGAAGTGTCAGCA (SEQ ID NO:916)
>HSMUC1A_0_0_11365
AATTAACCCTTTGAGAGCTGGCCAGGACTCTGGACTGATTACCCCAGCCT (SEQ ID NO:917)

The following list of abbreviations for tissues was used in the TAA histograms. The term “TAA” stands for “Tumor Associated Antigen”, and the TAA histograms, given in the text, represent the cancerous tissue expression pattern as predicted by the biomarkers selection engine, as described in detail in examples 1-5 below.

“BONE” for “bone”;
 “COL” for “colon”;
 “EPI” for “epithelial”;
 “GEN” for “general”;
 “LIVER” for “liver”;
 “LUN” for “lung”;
 “LYMPH” for “lymph nodes”;
 “MARROW” for “bone marrow”;
 “OVA” for “ovary”;
 “PANCREAS” for “pancreas”;
 “PRO” for “prostate”;
 “STOMACH” for  “stomach”;
 “TCELL” for “T cells”;
 “THYROID” for “Thyroid”;
 “MAM” for “breast”;
 “BRAIN” for “brain”;
 “UTERUS” for “uterus”;
 “SKIN” for “skin”;
 “KIDNEY” for “kidney”;
 “MUSCLE” for  “muscle”;
 “ADREN” for “adrenal”;
 “HEAD” for “head and neck”;
 “BLADDER” for  “bladder”;

It should be noted that the terms “segment”, “seg” and “node” are used interchangeably in reference to nucleic acid sequences of the present invention, they refer to portions of nucleic acid sequences that were shown to have one or more properties as described below. They are also the building blocks that were used to construct complete nucleic acid sequences as described in greater detail below. Optionally and preferably, they are examples of oligonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary oligonucleotides may optionally be derived, and/or for any other use.

As used herein the phrase “breast cancer” refers to cancers of the breast or surrounding tissue, including but not limited to ductal carcinoma (in-situ or invasive), lobular carcinoma (in-situ or invasive), inflammatory breast cancer, mucinous carcinoma, tubular carcinoma, or Paget's disease of the nipple, as well as conditions that are indicative of a higher risk factor for later development of breast cancer, including but not limited to ductal hyperplasia without atypia and atypical hyperplasia, referred to herein collectively as “indicative conditions”.

The term “marker” in the context of the present invention refers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from subjects (patients) having breast cancer (or one of the above indicative conditions) as compared to a comparable sample taken from subjects who do not have breast cancer (or one of the above indicative conditions).

The phrase “differentially present” refers to differences in the quantity of a marker present in a sample taken from patients having breast cancer (or one of the above indicative conditions) as compared to a comparable sample taken from patients who do not have breast cancer (or one of the above indicative conditions). For example, a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in the other sample, for example as measured by hybridization and/or NAT-based assays. A polypeptide is differentially present between the two samples if the amount of the polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present.

As used herein the phrase “diagnostic” means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity. The “sensitivity” of a diagnostic assay is the percentage of diseased individuals who test positive (percent of “true positives”). Diseased individuals not detected by the assay are “false negatives.” Subjects who are not diseased and who test negative in the assay are termed “true negatives.” The “specificity” of a diagnostic assay is 1 minus the false positive rate, where the “false positive” rate is defined as the proportion of those without the disease who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it suffices if the method provides a positive indication that aids in diagnosis.

As used herein the phrase “diagnosing” refers to classifying a disease or a symptom, determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery. The term “detecting” may also optionally encompass any of the above.

Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease. It should be noted that a “biological sample obtained from the subject” may also optionally comprise a sample that has not been physically removed from the subject, as described in greater detail below.

As used herein, the term “level” refers to expression levels of RNA and/or protein or to DNA copy number of a marker of the present invention.

Typically the level of the marker in a biological sample obtained from the subject is different (i.e., increased or decreased) from the level of the same variant in a similar sample obtained from a healthy individual (examples of biological samples are described herein).

Numerous well known tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and/or polypeptide of the variant of interest in the subject.

Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy/sample is obtained the level of the variant can be determined and a diagnosis can thus be made.

Determining the level of the same variant in normal tissues of the same origin is preferably effected along-side to detect an elevated expression and/or amplification and/or a decreased expression, of the variant as opposed to the normal tissues.

A “test amount” of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of breast cancer (or one of the above indicative conditions). A test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).

A “control amount” of a marker can be any amount or a range of amounts to be compared against a test amount of a marker. For example, a control amount of a marker can be the amount of a marker in a patient with breast cancer (or one of the above indicative conditions) or a person without breast cancer (or one of the above indicative conditions). A control amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals). “Detect” refers to identifying the presence, absence or amount of the object to be detected.

A “label” includes any moiety or item detectable by spectroscopic, photo chemical, biochemical, immunochemical, or chemical means. For example, useful labels include 32P, 35S, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin-streptavadin, dioxigenin, haptens and proteins for which antisera or monoclonal antibodies are available, or nucleic acid molecules with a sequence complementary to a target. The label often generates a measurable signal, such as a radioactive, chromogenic, or fluorescent signal, that can be used to quantify the amount of bound label in a sample. The label can be incorporated in or attached to a primer or probe either covalently, or through ionic, van der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides, or biotinylated nucleotides that are recognized by streptavadin. The label may be directly or indirectly detectable. Indirect detection can involve the binding of a second label to the first label, directly or indirectly. For example, the label can be the ligand of a binding partner, such as biotin, which is a binding partner for streptavadin, or a nucleotide sequence, which is the binding partner for a complementary sequence, to which it can specifically hybridize. The binding partner may itself be directly detectable, for example, an antibody may be itself labeled with a fluorescent molecule. The binding partner also may be indirectly detectable, for example, a nucleic acid having a complementary nucleotide sequence can be a part of a branched DNA molecule that is in turn detectable through hybridization with other labeled nucleic acid molecules (see, e.g., P. D. Fahrlander and A. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is achieved by, e.g., scintillation counting, densitometry, or flow cytometry.

Exemplary detectable labels, optionally and preferably for use with immunoassays, include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.

“Immunoassay” is an assay that uses an antibody to specifically bind an antigen. The immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen.

The phrase “specifically (or selectively) binds” to an antibody or “specifically (or selectively) immunoreactive with,” when referring to a protein or peptide (or other epitope), refers to a binding reaction that is determinative of the presence of the protein in a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample. Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein. For example, polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic variants and alleles of seminal basic protein. This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity). Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
T10888_PEA_1_T1 (SEQ ID NO: 1)
T10888_PEA_1_T4 (SEQ ID NO: 2)
T10888_PEA_1_T5 (SEQ ID NO: 3)
T10888_PEA_1_T6 (SEQ ID NO: 4)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
T10888_PEA_1_node_11 (SEQ ID NO: 5)
T10888_PEA_1_node_12 (SEQ ID NO: 6)
T10888_PEA_1_node_17 (SEQ ID NO: 7)
T10888_PEA_1_node_4 (SEQ ID NO: 8)
T10888_PEA_1_node_6 (SEQ ID NO: 9)
T10888_PEA_1_node_7 (SEQ ID NO: 10)
T10888_PEA_1_node_9 (SEQ ID NO: 11)
T10888_PEA_1_node_15 (SEQ ID NO: 12)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below amino acid sequence comprising a sequence in the table below:

Protein Name
T10888_PEA_1_P2 (SEQ ID NO: 14)
T10888_PEA_1_P4 (SEQ ID NO: 15)
T10888_PEA_1_P5 (SEQ ID NO: 16)
T10888_PEA_1_P6 (SEQ ID NO: 17)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
T39971_T10 (SEQ ID NO: 18)
T39971_T12 (SEQ ID NO: 19)
T39971_T16 (SEQ ID NO: 20)
T39971_T5 (SEQ ID NO: 21)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
T39971_node_0 (SEQ ID NO: 22)
T39971_node_18 (SEQ ID NO: 23)
T39971_node_21 (SEQ ID NO: 24)
T39971_node_22 (SEQ ID NO: 25)
T39971_node_23 (SEQ ID NO: 26)
T39971_node_31 (SEQ ID NO: 27)
T39971_node_33 (SEQ ID NO: 28)
T39971_node_7 (SEQ ID NO: 29)
T39971_node_1 (SEQ ID NO: 30)
T39971_node_10 (SEQ ID NO: 31)
T39971_node_11 (SEQ ID NO: 32)
T39971_node_12 (SEQ ID NO: 33)
T39971_node_15 (SEQ ID NO: 34)
T39971_node_16 (SEQ ID NO: 35)
T39971_node_17 (SEQ ID NO: 36)
T39971_node_26 (SEQ ID NO: 37)
T39971_node_27 (SEQ ID NO: 38)
T39971_node_28 (SEQ ID NO: 39)
T39971_node_29 (SEQ ID NO: 40)
T39971_node_3 (SEQ ID NO: 41)
T39971_node_30 (SEQ ID NO: 42)
T39971_node_34 (SEQ ID NO: 43)
T39971_node_35 (SEQ ID NO: 44)
T39971_node_36 (SEQ ID NO: 45)
T39971_node_4 (SEQ ID NO: 46)
T39971_node_5 (SEQ ID NO: 47)
T39971_node_8 (SEQ ID NO: 48)
T39971_node_9 (SEQ ID NO: 49)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name
T39971_P6 (SEQ ID NO: 51)
T39971_P9 (SEQ ID NO: 52)
T39971_P11 (SEQ ID NO: 53)
T39971_P12 (SEQ ID NO: 54)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
Z21368_PEA_1_T10 (SEQ ID NO: 55)
Z21368_PEA_1_T11 (SEQ ID NO: 56)
Z21368_PEA_1_T23 (SEQ ID NO: 57)
Z21368_PEA_1_T24 (SEQ ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID NO: 59)
Z21368_PEA_1_T6 (SEQ ID NO: 60)
Z21368_PEA_1_T9 (SEQ ID NO: 61)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
Z21368_PEA_1_node_0 (SEQ ID NO: 62)
Z21368_PEA_1_node_15 (SEQ ID NO: 63)
Z21368_PEA_1_node_19 (SEQ ID NO: 64)
Z21368_PEA_1_node_2 (SEQ ID NO: 65)
Z21368_PEA_1_node_21 (SEQ ID NO: 66)
Z21368_PEA_1_node_33 (SEQ ID NO: 67)
Z21368_PEA_1_node_36 (SEQ ID NO: 68)
Z21368_PEA_1_node_37 (SEQ ID NO: 69)
Z21368_PEA_1_node_39 (SEQ ID NO: 70)
Z21368_PEA_1_node_4 (SEQ ID NO: 71)
Z21368_PEA_1_node_41 (SEQ ID NO: 72)
Z21368_PEA_1_node_43 (SEQ ID NO: 73)
Z21368_PEA_1_node_45 (SEQ ID NO: 74)
Z21368_PEA_1_node_53 (SEQ ID NO: 75)
Z21368_PEA_1_node_56 (SEQ ID NO: 76)
Z21368_PEA_1_node_58 (SEQ ID NO: 77)
Z21368_PEA_1_node_66 (SEQ ID NO: 78)
Z21368_PEA_1_node_67 (SEQ ID NO: 79)
Z21368_PEA_1_node_69 (SEQ ID NO: 80)
Z21368_PEA_1_node_11 (SEQ ID NO: 81)
Z21368_PEA_1_node_12 (SEQ ID NO: 82)
Z21368_PEA_1_node_16 (SEQ ID NO: 83)
Z21368_PEA_1_node_17 (SEQ ID NO: 84)
Z21368_PEA_1_node_23 (SEQ ID NO: 85)
Z21368_PEA_1_node_24 (SEQ ID NO: 86)
Z21368_PEA_1_node_30 (SEQ ID NO: 87)
Z21368_PEA_1_node_31 (SEQ ID NO: 88)
Z21368_PEA_1_node_38 (SEQ ID NO: 89)
Z21368_PEA_1_node_47 (SEQ ID NO: 90)
Z21368_PEA_1_node_49 (SEQ ID NO: 91)
Z21368_PEA_1_node_51 (SEQ ID NO: 92)
Z21368_PEA_1_node_61 (SEQ ID NO: 93)
Z21368_PEA_1_node_68 (SEQ ID NO: 94)
Z21368_PEA_1_node_7 (SEQ ID NO: 95)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
Z21368_PEA_1_P2 (SEQ ID NO: 97)
Z21368_PEA_1_P5 (SEQ ID NO: 98)
Z21368_PEA_1_P15 (SEQ ID NO: 99)
Z21368_PEA_1_P16 (SEQ ID NO: 100)
Z21368_PEA_1_P22 (SEQ ID NO: 101)
Z21368_PEA_1_P23 (SEQ ID NO: 102)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
T59832_T11 (SEQ ID NO: 103)
T59832_T15 (SEQ ID NO: 104)
T59832_T22 (SEQ ID NO: 105)
T59832_T28 (SEQ ID NO: 106)
T59832_T6 (SEQ ID NO: 107)
T59832_T8 (SEQ ID NO: 108)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
T59832_node_1 (SEQ ID NO: 109)
T59832_node_22 (SEQ ID NO: 110)
T59832_node_23 (SEQ ID NO: 111)
T59832_node_24 (SEQ ID NO: 112)
T59832_node_29 (SEQ ID NO: 113)
T59832_node_39 (SEQ ID NO: 114)
T59832_node_7 (SEQ ID NO: 115)
T59832_node_10 (SEQ ID NO: 116)
T59832_node_11 (SEQ ID NO: 117)
T59832_node_12 (SEQ ID NO: 118)
T59832_node_14 (SEQ ID NO: 119)
T59832_node_16 (SEQ ID NO: 120)
T59832_node_19 (SEQ ID NO: 121)
T59832_node_2 (SEQ ID NO: 122)
T59832_node_20 (SEQ ID NO: 123)
T59832_node_25 (SEQ ID NO: 124)
T59832_node_26 (SEQ ID NO: 125)
T59832_node_27 (SEQ ID NO: 126)
T59832_node_28 (SEQ ID NO: 127)
T59832_node_3 (SEQ ID NO: 128)
T59832_node_30 (SEQ ID NO: 129)
T59832_node_31 (SEQ ID NO: 130)
T59832_node_32 (SEQ ID NO: 131)
T59832_node_34 (SEQ ID NO: 132)
T59832_node_35 (SEQ ID NO: 133)
T59832_node_36 (SEQ ID NO: 134)
T59832_node_37 (SEQ ID NO: 135)
T59832_node_38 (SEQ ID NO: 136)
T59832_node_4 (SEQ ID NO: 137)
T59832_node_5 (SEQ ID NO: 138)
T59832_node_6 (SEQ ID NO: 139)
T59832_node_8 (SEQ ID NO: 140)
T59832_node_9 (SEQ ID NO: 141)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
T59832_P5 (SEQ ID NO: 143)
T59832_P7 (SEQ ID NO: 144)
T59832_P9 (SEQ ID NO: 145)
T59832_P12 (SEQ ID NO: 146)
T59832_P18 (SEQ ID NO: 147)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
Z41644_PEA_1_T5 (SEQ ID NO: 208)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
Z41644_PEA_1_node_0 (SEQ ID NO: 209)
Z41644_PEA_1_node_11 (SEQ ID NO: 210)
Z41644_PEA_1_node_12 (SEQ ID NO: 211)
Z41644_PEA_1_node_15 (SEQ ID NO: 212)
Z41644_PEA_1_node_20 (SEQ ID NO: 213)
Z41644_PEA_1_node_24 (SEQ ID NO: 214)
Z41644_PEA_1_node_1 (SEQ ID NO: 215)
Z41644_PEA_1_node_10 (SEQ ID NO: 216)
Z41644_PEA_1_node_13 (SEQ ID NO: 217)
Z41644_PEA_1_node_16 (SEQ ID NO: 218)
Z41644_PEA_1_node_17 (SEQ ID NO: 219)
Z41644_PEA_1_node_19 (SEQ ID NO: 220)
Z41644_PEA_1_node_2 (SEQ ID NO: 221)
Z41644_PEA_1_node_21 (SEQ ID NO: 222)
Z41644_PEA_1_node_22 (SEQ ID NO: 223)
Z41644_PEA_1_node_23 (SEQ ID NO: 224)
Z41644_PEA_1_node_25 (SEQ ID NO: 225)
Z41644_PEA_1_node_3 (SEQ ID NO: 226)
Z41644_PEA_1_node_4 (SEQ ID NO: 227)
Z41644_PEA_1_node_6 (SEQ ID NO: 228)
Z41644_PEA_1_node_9 (SEQ ID NO: 229)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
Z41644_PEA_1_P10 (SEQ ID NO: 231)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HUMGRP5E_T4 (SEQ ID NO:148)
HUMGRP5E_T5 (SEQ ID NO:149)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HUMGRP5E_node_0 (SEQ ID NO:150)
HUMGRP5E_node_2 (SEQ ID NO:151)
HUMGRP5E_node_8 (SEQ ID NO:152)
HUMGRP5E_node_3 (SEQ ID NO:153)
HUMGRP5E_node_7 (SEQ ID NO:154)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HUMGRP5E_P4 (SEQ ID NO:156)
HUMGRP5E_P5 (SEQ ID NO:157)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
AA155578_PEA_1_T10 (SEQ ID NO: 158)
AA155578_PEA_1_T12 (SEQ ID NO: 159)
AA155578_PEA_1_T13 (SEQ ID NO: 160)
AA155578_PEA_1_T8 (SEQ ID NO: 161)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
AA155578_PEA_1_node_11 (SEQ ID
NO: 162)
AA155578_PEA_1_node_12 (SEQ ID
NO: 163)
AA155578_PEA_1_node_14 (SEQ ID
NO: 164)
AA155578_PEA_1_node_19 (SEQ ID
NO: 165)
AA155578_PEA_1_node_21 (SEQ ID
NO: 166)
AA155578_PEA_1_node_23 (SEQ ID
NO: 167)
AA155578_PEA_1_node_24 (SEQ ID
NO: 168)
AA155578_PEA_1_node_25 (SEQ ID
NO: 169)
AA155578_PEA_1_node_4 (SEQ ID NO: 170)
AA155578_PEA_1_node_7 (SEQ ID NO: 171)
AA155578_PEA_1_node_15 (SEQ ID
NO: 172)
AA155578_PEA_1_node_18 (SEQ ID
NO: 173)
AA155578_PEA_1_node_22 (SEQ ID
NO: 174)
AA155578_PEA_1_node_6 (SEQ ID NO: 175)
AA155578_PEA_1_node_8 (SEQ ID NO: 176)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
AA155578_PEA_1_P4 (SEQ ID NO: 178)
AA155578_PEA_1_P6 (SEQ ID NO: 179)
AA155578_PEA_1_P8 (SEQ ID NO: 180)
AA155578_PEA_1_P9 (SEQ ID NO: 181)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HSENA78_T5 (SEQ ID NO:182)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HSENA78_node_0 (SEQ ID NO:183)
HSENA78_node_2 (SEQ ID NO:184)
HSENA78_node_6 (SEQ ID NO:185)
HSENA78_node_9 (SEQ ID NO:186)
HSENA78_node_3 (SEQ ID NO:187)
HSENA78_node_4 (SEQ ID NO:188)
HSENA78_node_8 (SEQ ID NO:189)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name
HSENA78_P2 (SEQ ID NO:191)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
T94936_PEA_1_T1 (SEQ ID NO: 192)
T94936_PEA_1_T2 (SEQ ID NO: 193)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
T94936_PEA_1_node_14 (SEQ ID NO: 194)
T94936_PEA_1_node_16 (SEQ ID NO: 195)
T94936_PEA_1_node_2 (SEQ ID NO: 196)
T94936_PEA_1_node_20 (SEQ ID NO: 197)
T94936_PEA_1_node_23 (SEQ ID NO: 198)
T94936_PEA_1_node_0 (SEQ ID NO: 199)
T94936_PEA_1_node_11 (SEQ ID NO: 200)
T94936_PEA_1_node_13 (SEQ ID NO: 201)
T94936_PEA_1_node_17 (SEQ ID NO: 202)
T94936_PEA_1_node_6 (SEQ ID NO: 203)
T94936_PEA_1_node_8 (SEQ ID NO: 204)
T94936_PEA_1_node_9 (SEQ ID NO: 205)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
T94936_PEA_1_P2 (SEQ ID NO: 206)
T94936_PEA_1_P3 (SEQ ID NO: 207)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
M85491_PEA_1_T16 (SEQ ID NO: 232)
M85491_PEA_1_T20 (SEQ ID NO: 233)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
M85491_PEA_1_node_0 (SEQ ID NO: 234)
M85491_PEA_1_node_13 (SEQ ID NO: 235)
M85491_PEA_1_node_21 (SEQ ID NO: 236)
M85491_PEA_1_node_23 (SEQ ID NO: 237)
M85491_PEA_1_node_24 (SEQ ID NO: 238)
M85491_PEA_1_node_8 (SEQ ID NO: 239)
M85491_PEA_1_node_9 (SEQ ID NO: 240)
M85491_PEA_1_node_10 (SEQ ID NO: 241)
M85491_PEA_1_node_18 (SEQ ID NO: 242)
M85491_PEA_1_node_19 (SEQ ID NO: 243)
M85491_PEA_1_node_6 (SEQ ID NO: 244)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
M85491_PEA_1_P13 (SEQ ID NO: 246)
M85491_PEA_1_P14 (SEQ ID NO: 247)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HSSTROL3_T5 (SEQ ID NO:248)
HSSTROL3_T8 (SEQ ID NO:249)
HSSTROL3_T9 (SEQ ID NO:250)
HSSTROL3_T10 (SEQ ID NO:251)
HSSTROL3_T11 (SEQ ID NO:252)
HSSTROL3_T12 (SEQ ID NO:253)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HSSTROL3_node_6 (SEQ ID NO:254)
HSSTROL3_node_10 (SEQ ID NO:255)
HSSTROL3_node_13 (SEQ ID NO:256)
HSSTROL3_node_15 (SEQ ID NO:257)
HSSTROL3_node_19 (SEQ ID NO:258)
HSSTROL3_node_21 (SEQ ID NO:259)
HSSTROL3_node_24 (SEQ ID NO:260)
HSSTROL3_node_25 (SEQ ID NO:261)
HSSTROL3_node_26 (SEQ ID NO:262)
HSSTROL3_node_28 (SEQ ID NO:263)
HSSTROL3_node_29 (SEQ ID NO:264)
HSSTROL3_node_11 (SEQ ID NO:265)
HSSTROL3_node_17 (SEQ ID NO:266)
HSSTROL3_node_18 (SEQ ID NO:267)
HSSTROL3_node_20 (SEQ ID NO:268)
HSSTROL3_node_27 (SEQ ID NO:269)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HSSTROL3_P4 (SEQ ID NO:271)
HSSTROL3_P5 (SEQ ID NO:272)
HSSTROL3_P7 (SEQ ID NO:273)
HSSTROL3_P8 (SEQ ID NO:274)
HSSTROL3_P9 (SEQ ID NO:275)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
AY180924_PEA_1_T1 (SEQ ID NO: 276)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
AY180924_PEA_1_node_3 (SEQ ID NO: 277)
AY180924_PEA_1_node_0 (SEQ ID NO: 278)
AY180924_PEA_1_node_2 (SEQ ID NO: 279)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
AY180924_PEA_1_P3 (SEQ ID NO: 281)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
R75793_PEA_1_T1 (SEQ ID NO: 282)
R75793_PEA_1_T3 (SEQ ID NO: 283)
R75793_PEA_1_T5 (SEQ ID NO: 284)

a nucleic acid sequence comprising a sequence in the table below:

R75793_PEA_1_node_0 (SEQ ID NO: 285)
R75793_PEA_1_node_9 (SEQ ID NO: 286)
R75793_PEA_1_node_11 (SEQ ID NO: 287)
R75793_PEA_1_node_14 (SEQ ID NO: 288)
R75793_PEA_1_node_4 (SEQ ID NO: 289)
R75793_PEA_1_node_5 (SEQ ID NO: 290)
R75793_PEA_1_node_6 (SEQ ID NO: 291)
R75793_PEA_1_node_8 (SEQ ID NO: 292)
R75793_PEA_1_node_13 (SEQ ID NO: 293)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
R75793_PEA_1_P2 (SEQ ID NO: 295)
R75793_PEA_1_P5 (SEQ ID NO: 296)
R75793_PEA_1_P6 (SEQ ID NO: 297)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HUMCA1XIA_T16 (SEQ ID NO:298)
HUMCA1XIA_T17 (SEQ ID NO:299)
HUMCA1XIA_T19 (SEQ ID NO:300)
HUMCA1XIA_T20 (SEQ ID NO:301)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HUMCA1XIA_node_0 (SEQ ID NO:302)
HUMCA1XIA_node_2 (SEQ ID NO:303)
HUMCA1XIA_node_4 (SEQ ID NO:304)
HUMCA1XIA_node_6 (SEQ ID NO:305)
HUMCA1XIA_node_8 (SEQ ID NO:306)
HUMCA1XIA_node_9 (SEQ ID NO:307)
HUMCA1XIA_node_18 (SEQ ID NO:308)
HUMCA1XIA_node_54 (SEQ ID NO:309)
HUMCA1XIA_node_55 (SEQ ID NO:310)
HUMCA1XIA_node_92 (SEQ ID NO:311)
HUMCA1XIA_node_11 (SEQ ID NO:312)
HUMCA1XIA_node_15 (SEQ ID NO:313)
HUMCA1XIA_node_19 (SEQ ID NO:314)
HUMCA1XIA_node_21 (SEQ ID NO:315)
HUMCA1XIA_node_23 (SEQ ID NO:316)
HUMCA1XIA_node_25 (SEQ ID NO:317)
HUMCA1XIA_node_27 (SEQ ID NO:318)
HUMCA1XIA_node_29 (SEQ ID NO:319)
HUMCA1XIA_node_31 (SEQ ID NO:320)
HUMCA1XIA_node_33 (SEQ ID NO:321)
HUMCA1XIA_node_35 (SEQ ID NO:322)
HUMCA1XIA_node_37 (SEQ ID NO:323)
HUMCA1XIA_node_39 (SEQ ID NO:324)
HUMCA1XIA_node_41 (SEQ ID NO:325)
HUMCA1XIA_node_43 (SEQ ID NO:326)
HUMCA1XIA_node_45 (SEQ ID NO:327)
HUMCA1XIA_node_47 (SEQ ID NO:328)
HUMCA1XIA_node_49 (SEQ ID NO:329)
HUMCA1XIA_node_51 (SEQ ID NO:330)
HUMCA1XIA_node_57 (SEQ ID NO:331)
HUMCA1XIA_node_59 (SEQ ID NO:332)
HUMCA1XIA_node_62 (SEQ ID NO:333)
HUMCA1XIA_node_64 (SEQ ID NO:334)
HUMCA1XIA_node_66 (SEQ ID NO:335)
HUMCA1XIA_node_68 (SEQ ID NO:336)
HUMCA1XIA_node_70 (SEQ ID NO:337)
HUMCA1XIA_node_72 (SEQ ID NO:338)
HUMCA1XIA_node_74 (SEQ ID NO:339)
HUMCA1XIA_node_76 (SEQ ID NO:340)
HUMCA1XIA_node_78 (SEQ ID NO:341)
HUMCA1XIA_node_81 (SEQ ID NO:342)
HUMCA1XIA_node_83 (SEQ ID NO:343)
HUMCA1XIA_node_85 (SEQ ID NO:344)
HUMCA1XIA_node_87 (SEQ ID NO:345)
HUMCA1XIA_node_89 (SEQ ID NO:346)
HUMCA1XIA_node_91 (SEQ ID NO:347)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HUMCA1XIA_P14 (SEQ ID NO:350)
HUMCA1XIA_P15 (SEQ ID NO:351)
HUMCA1XIA_P16 (SEQ ID NO:352)
HUMCA1XIA_P17 (SEQ ID NO:353)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
R20779_T7 (SEQ ID NO: 354)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
R20779_node_0 (SEQ ID NO: 355)
R20779_node_2 (SEQ ID NO: 356)
R20779_node_7 (SEQ ID NO: 357)
R20779_node_9 (SEQ ID NO: 358)
R20779_node_18 (SEQ ID NO: 359)
R20779_node_21 (SEQ ID NO: 360)
R20779_node_24 (SEQ ID NO: 361)
R20779_node_27 (SEQ ID NO: 362)
R20779_node_28 (SEQ ID NO: 363)
R20779_node_30 (SEQ ID NO: 364)
R20779_node_31 (SEQ ID NO: 365)
R20779_node_32 (SEQ ID NO: 366)
R20779_node_1 (SEQ ID NO: 367)
R20779_node_3 (SEQ ID NO: 368)
R20779_node_10 (SEQ ID NO: 369)
R20779_node_11 (SEQ ID NO: 370)
R20779_node_14 (SEQ ID NO: 371)
R20779_node_17 (SEQ ID NO: 372)
R20779_node_19 (SEQ ID NO: 373)
R20779_node_20 (SEQ ID NO: 374)
R20779_node_22 (SEQ ID NO: 375)
R20779_node_23 (SEQ ID NO: 376)
R20779_node_25 (SEQ ID NO: 377)
R20779_node_29 (SEQ ID NO: 378)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence according to R20779_P2 (SEQ ID NO:380).

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HSS100PCB_T1 (SEQ ID NO:381)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HSS100PCB_node_3 (SEQ ID NO:382)
HSS100PCB_node_4 (SEQ ID NO:383)
HSS100PCB_node_5 (SEQ ID NO:384)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence according to HSS100PCB_P3 (SEQ ID NO:386).

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HSCOC4_PEA_1_T1 (SEQ ID NO:387)
HSCOC4_PEA_1_T2 (SEQ ID NO:388)
HSCOC4_PEA_1_T3 (SEQ ID NO:389)
HSCOC4_PEA_1_T4 (SEQ ID NO:390)
HSCOC4_PEA_1_T5 (SEQ ID NO:391)
HSCOC4_PEA_1_T7 (SEQ ID NO:392)
HSCOC4_PEA_1_T8 (SEQ ID NO:393)
HSCOC4_PEA_1_T11 (SEQ ID NO:394)
HSCOC4_PEA_1_T12 (SEQ ID NO:395)
HSCOC4_PEA_1_T14 (SEQ ID NO:396)
HSCOC4_PEA_1_T15 (SEQ ID NO:397)
HSCOC4_PEA_1_T20 (SEQ ID NO:398)
HSCOC4_PEA_1_T21 (SEQ ID NO:399)
HSCOC4_PEA_1_T25 (SEQ ID NO:400)
HSCOC4_PEA_1_T28 (SEQ ID NO:401)
HSCOC4_PEA_1_T30 (SEQ ID NO:402)
HSCOC4_PEA_1_T31 (SEQ ID NO:403)
HSCOC4_PEA_1_T32 (SEQ ID NO:404)
HSCOC4_PEA_1_T40 (SEQ ID NO:405)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HSCOC4_PEA_1_node_1 (SEQ ID NO:406)
HSCOC4_PEA_1_node_5 (SEQ ID NO:407)
HSCOC4_PEA_1_node_7 (SEQ ID NO:408)
HSCOC4_PEA_1_node_30 (SEQ ID NO:409)
HSCOC4_PEA_1_node_33 (SEQ ID NO:410)
HSCOC4_PEA_1_node_35 (SEQ ID NO:411)
HSCOC4_PEA_1_node_37 (SEQ ID NO:412)
HSCOC4_PEA_1_node_39 (SEQ ID NO:413)
HSCOC4_PEA_1_node_43 (SEQ ID NO:414)
HSCOC4_PEA_1_node_48 (SEQ ID NO:415)
HSCOC4_PEA_1_node_49 (SEQ ID NO:416)
HSCOC4_PEA_1_node_51 (SEQ ID NO:417)
HSCOC4_PEA_1_node_58 (SEQ ID NO:418)
HSCOC4_PEA_1_node_59 (SEQ ID NO:419)
HSCOC4_PEA_1_node_62 (SEQ ID NO:420)
HSCOC4_PEA_1_node_66 (SEQ ID NO:421)
HSCOC4_PEA_1_node_72 (SEQ ID NO:422)
HSCOC4_PEA_1_node_77 (SEQ ID NO:423)
HSCOC4_PEA_1_node_79 (SEQ ID NO:424)
HSCOC4_PEA_1_node_93 (SEQ ID NO:425)
HSCOC4_PEA_1_node_100 (SEQ ID NO:426)
HSCOC4_PEA_1_node_105 (SEQ ID NO:427)
HSCOC4_PEA_1_node_107 (SEQ ID NO:428)
HSCOC4_PEA_1_node_108 (SEQ ID NO:429)
HSCOC4_PEA_1_node_109 (SEQ ID NO:430)
HSCOC4_PEA_1_node_110 (SEQ ID NO:431)
HSCOC4_PEA_1_node_112 (SEQ ID NO:432)
HSCOC4_PEA_1_node_113 (SEQ ID NO:433)
HSCOC4_PEA_1_node_2 (SEQ ID NO:434)
HSCOC4_PEA_1_node_8 (SEQ ID NO:435)
HSCOC4_PEA_1_node_10 (SEQ ID NO:436)
HSCOC4_PEA_1_node_12 (SEQ ID NO:437)
HSCOC4_PEA_1_node_14 (SEQ ID NO:438)
HSCOC4_PEA_1_node_17 (SEQ ID NO:439)
HSCOC4_PEA_1_node_19 (SEQ ID NO:440)
HSCOC4_PEA_1_node_21 (SEQ ID NO:441)
HSCOC4_PEA_1_node_22 (SEQ ID NO:442)
HSCOC4_PEA_1_node_28 (SEQ ID NO:443)
HSCOC4_PEA_1_node_29 (SEQ ID NO:444)
HSCOC4_PEA_1_node_41 (SEQ ID NO:445)
HSCOC4_PEA_1_node_45 (SEQ ID NO:446)
HSCOC4_PEA_1_node_47 (SEQ ID NO:447)
HSCOC4_PEA_1_node_50 (SEQ ID NO:448)
HSCOC4_PEA_1_node_53 (SEQ ID NO:449)
HSCQC4_PEA_1_node_55 (SEQ ID NO:450)
HSCOC4_PEA_1_node_57 (SEQ ID NO:451)
HSCOC4_PEA_1_node_60 (SEQ ID NO:452)
HSCOC4_PEA_1_node_64 (SEQ ID NO:453)
HSCOC4_PEA_1_node_69 (SEQ ID NO:454)
HSCOC4_PEA_1_node_70 (SEQ ID NO:455)
HSCOC4_PEA_1_node_71 (SEQ ID NO:456)
HSCOC4_PEA_1_node_73 (SEQ ID NO:457)
HSCOC4_PEA_1_node_74 (SEQ ID NO:458)
HSCOC4_PEA_1_node_75 (SEQ ID NO:459)
HSCOC4_PEA_1_node_76 (SEQ ID NO:460)
HSCOC4_PEA_1_node_78 (SEQ ID NO:461)
HSCOC4_PEA_1_node_80 (SEQ ID NO:462)
RSCOC4_PEA_1_node_82 (SEQ ID NO:463)
HSCOC4_PEA_1_node_83 (SEQ ID NO:464)
HSCOC4_PEA_1_node_84 (SEQ ID NO:465)
HSCOC4_PEA_1_node_85 (SEQ ID NO:466)
HSCOC4_PEA_1_node_86 (SEQ ID NO:467)
HSCOC4_PEA_1_node_87 (SEQ ID NO:468)
HSCOC4_PEA_1_node_88 (SEQ ID NO:469)
HSCOC4_PEA_1_node_89 (SEQ ID NO:470)
HSCOC4_PEA_1_node_90 (SEQ ID NO:471)
HSCOC4_PEA_1_node_91 (SEQ ID NO:472)
HSCOC4_PEA_1_node_92 (SEQ ID NO:473)
HSCOC4_PEA_1_node_94 (SEQ ID NO:474)
HSCOC4_PEA_1_node_96 (SEQ ID NO:475)
HSCOC4_PEA_1_node_97 (SEQ ID NO:476)
HSCOC4_PEA_1_node_98 (SEQ ID NO:477)
HSCOC4_PEA_1_node_99 (SEQ ID NO:478)
HSCOC4_PEA_1_node_101 (SEQ ID NO:479)
HSCOC4_PEA_1_node_102 (SEQ ID NO:480)
HSCOC4_PEA_1_node_103 (SEQ ID NO:481)
HSCOC4_PEA_1_node_104 (SEQ ID NO:482)
HSCOC4_PEA_1_node_106 (SEQ ID NO:483)
HSCOC4_PEA_1_node_111 (SEQ ID NO:484)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HSCOC4_PEA_1_P3 (SEQ ID NO:488)
HSCOC4_PEA_1_P5 (SEQ ID NO:489)
HSCOC4_PEA_1_P6 (SEQ ID NO:490)
HSCOC4_PEA_1_P12 (SEQ ID NO:491)
HSCOC4_PEA_1_P15 (SEQ ID NO:492)
HSCOC4_PEA_1_P16 (SEQ ID NO:493)
HSCOC4_PEA_1_P20 (SEQ ID NO:494)
HSCOC4_PEA_1_P9 (SEQ ID NO:495)
HSCOC4_PEA_1_P22 (SEQ ID NO:496)
HSCOC4_PEA_1_P23 (SEQ ID NO:497)
HSCOC4_PEA_1_P24 (SEQ ID NO:498)
HSCOC4_PEA_1_P25 (SEQ ID NO:499)
HSCOC4_PEA_1_P26 (SEQ ID NO:500)
HSCOC4_PEA_1_P30 (SEQ ID NO:501)
HSCOC4_PEA_1_P38 (SEQ ID NO:502)
HSCOC4_PEA_1_P39 (SEQ ID NO:503)
HSCOC4_PEA_1_P40 (SEQ ID NO:504)
HSCOC4_PEA_1_P41 (SEQ ID NO:505)
HSCOC4_PEA_1_P42 (SEQ ID NO:506)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HUMTREFAC_PEA_2_T4 (SEQ ID NO:507)
HUMTREFAC_PEA_2_T5 (SEQ ID NO:508)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HUMTREFAC_PEA_2_node_0 (SEQ ID NO:509)
HUMTREFAC_PEA_2_node_9 (SEQ ID NO:510)
HUMTREFAC_PEA_2_node_2 (SEQ ID NO:511)
HUMTREFAC_PEA_2_node_3 (SEQ ID NO:512)
HUMTREFAC_PEA_2_node_4 (SEQ ID NO:513)
HUMTREFAC_PEA_2_node_5 (SEQ ID NO:514)
HUMTREFAC_PEA_2_node_8 (SEQ ID NO:515)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HUMTREFAC_PEA_2_P7 (SEQ ID NO:517)
HUMTREFAC_PEA_2_P8 (SEQ ID NO:518)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HUMOSTRO_PEA_1_PEA_1_T14 (SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 (SEQ ID NO:520)
HUMOSTRO_PEA_1_PEA_1_T30 (SEQ ID NO:521)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HUMOSTRO_PEA_1_PEA_1_node_0 (SEQ ID NO:522)
HUMOSTRO_PEA_1_PEA_1_node_10 (SEQ ID NO:523)
HUMOSTRO_PEA_1_PEA_1_node_16 (SEQ ID NO:524)
HUMOSTRO_PEA_1_PEA_1_node_23 (SEQ ID NO:525)
HUMOSTRO_PEA_1_PEA_1_node_31 (SEQ ID NO:526)
HUMOSTRO_PEA_1_PEA_1_node_43 (SEQ ID NO:527)
HUMOSTRO_PEA_1_PEA_1_node_3 (SEQ ID NO:528)
HUMOSTRO_PEA_1_PEA_1_node_5 (SEQ ID NO:529)
HUMOSTRO_PEA_1_PEA_1_node_7 (SEQ ID NO:530)
HUMOSTRO_PEA_1_PEA_1_node_8 (SEQ ID NO:531)
HUMOSTRO_PEA_1_PEA_1_node_15 (SEQ ID NO:532)
HUMOSTRO_PEA_1_PEA_1_node_17 (SEQ ID NO:533)
HUMOSTRO_PEA_1_PEA_1_node_20 (SEQ ID NO:534)
HUMOSTRO_PEA_1_PEA_1_node_21 (SEQ ID NO:535)
HUMOSTRO_PEA_1_PEA_1_node_22 (SEQ ID NO:536)
HUMOSTRO_PEA_1_PEA_1_node_24 (SEQ ID NO:537)
HUMOSTRO_PEA_1_PEA_1_node_26 (SEQ ID NO:538)
HUMOSTRO_PEA_1_PEA_1_node_27 (SEQ ID NO:539)
HUMOSTRO_PEA_1_PEA_1_node_28 (SEQ ID NO:540)
HUMOSTRO_PEA_1_PEA_1_node_29 (SEQ ID NO:541)
HUMOSTRO_PEA_1_PEA_1_node_30 (SEQ ID NO:542)
HUMOSTRO_PEA_1_PEA_1_node_32 (SEQ ID NO:543)
HUMOSTRO_PEA_1_PEA_1_node_34 (SEQ ID NO:544)
HUMOSTRO_PEA_1_PEA_1_node_36 (SEQ ID NO:545)
HUMOSTRO_PEA_1_PEA_1_node_37 (SEQ ID NO:546)
HUMOSTRO_PEA_1_PEA_1_node_38 (SEQ ID NO:547)
HUMOSTRO_PEA_1_PEA_1_node_39 (SEQ ID NO:548)
HUMOSTRO_PEA_1_PEA_1_node_40 (SEQ ID NO:549)
HUMOSTRO_PEA_1_PEA_1_node_41 (SEQ ID NO:550)
HUMOSTRO_PEA_1_PEA_1_node_42 (SEQ ID NO:551)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HUMOSTRO_PEA_1_PEA_1_P21 (SEQ ID NO:553)
HUMOSTRO_PEA_1_PEA_1_P25 (SEQ ID NO:554)
HUMOSTRO_PEA_1_PEA_1_P30 (SEQ ID NO:555)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a polynucleotide having a sequence selected from the group consisting of: R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560), or R11723_PEA—1_T6 (SEQ ID NO:561).

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a node having a sequence selected from the group consisting of: R11723_PEA—1_node—13 (SEQ ID NO:562), R11723_PEA—1_node—16 (SEQ ID NO:563), R11723_PEA—1_node—19 (SEQ ID NO:564), R11723_PEA—1_node—2 (SEQ ID NO:565), R11723_PEA—1_node—22 (SEQ ID NO:566), R11723_PEA—1_node—31 (SEQ ID NO:567), R11723_PEA—1_node—10 (SEQ ID NO:568), R11723_PEA—1_node—11 (SEQ ID NO:569), R11723_PEA—1_node—15 (SEQ ID NO:570), R11723_PEA—1_node—18 (SEQ ID NO:571), R11723_PEA—1_node—20 (SEQ ID NO:572), R11723_PEA—1_node—21 (SEQ ID NO:573), R11723_PEA—1_node—23 (SEQ ID NO:574), R11723_PEA—1_node—24 (SEQ ID NO:575), R11723_PEA—1_node—25 (SEQ ID NO:576), R11723_PEA—1_node—26 (SEQ ID NO:577), R11723_PEA—1_node—27 (SEQ ID NO:578), R11723_PEA—1_node—28 (SEQ ID NO:579), R11723_PEA—1_node—29 (SEQ ID NO:580), R11723_PEA—1_node—3 (SEQ ID NO:581), R11723_PEA—1_node—30 (SEQ ID NO:582), R11723_PEA—1_node—4 (SEQ ID NO:583), R11723_PEA—1_node—5 (SEQ ID NO:584), R11723_PEA—1_node—6 (SEQ ID NO:585), R11723_PEA—1_node—7 (SEQ ID NO:586) or R11723_PEA—1_node—8 (SEQ ID NO:587).

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a polypeptide having a sequence selected from the group consisting of: R11723_PEA—113 P2 (SEQ ID NO:588), R11723_PEA—1_P6 (SEQ ID NO:589), R11723_PEA—1_P7 (SEQ ID NO:590), R11723_PEA—1_P13 (SEQ ID NO:591), or R11723_PEA—1_P10 (SEQ ID NO:592).

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
T46984_PEA_1_T2 (SEQ ID NO: 593)
T46984_PEA_1_T3 (SEQ ID NO: 594)
T46984_PEA_1_T12 (SEQ ID NO: 595)
T46984_PEA_1_T13 (SEQ ID NO: 596)
T46984_PEA_1_T14 (SEQ ID NO: 597)
T46984_PEA_1_T15 (SEQ ID NO: 598)
T46984_PEA_1_T19 (SEQ ID NO: 599)
T46984_PEA_1_T23 (SEQ ID NO: 600)
T46984_PEA_1_T27 (SEQ ID NO: 601)
T46984_PEA_1_T32 (SEQ ID NO: 602)
T46984_PEA_1_T34 (SEQ ID NO: 603)
T46984_PEA_1_T35 (SEQ ID NO: 604)
T46984_PEA_1_T40 (SEQ ID NO: 605)
T46984_PEA_1_T42 (SEQ ID NO: 606)
T46984_PEA_1_T43 (SEQ ID NO: 607)
T46984_PEA_1_T46 (SEQ ID NO: 608)
T46984_PEA_1_T47 (SEQ ID NO: 609)
T46984_PEA_1_T48 (SEQ ID NO: 610)
T46984_PEA_1_T51 (SEQ ID NO: 611)
T46984_PEA_1_T52 (SEQ ID NO: 612)
T46984_PEA_1_T54 (SEQ ID NO: 613)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
T46984_PEA_1_node_2 (SEQ ID NO: 614)
T46984_PEA_1_node_4 (SEQ ID NO: 615)
T46984_PEA_1_node_6 (SEQ ID NO: 616)
T46984_PEA_1_node_12 (SEQ ID NO: 617)
T46984_PEA_1_node_14 (SEQ ID NO: 618)
T46984_PEA_1_node_25 (SEQ ID NO: 619)
T46984_PEA_1_node_29 (SEQ ID NO: 620)
T46984_PEA_1_node_34 (SEQ ID NO: 621)
T46984_PEA_1_node_46 (SEQ ID NO: 622)
T46984_PEA_1_node_47 (SEQ ID NO: 623)
T46984_PEA_1_node_52 (SEQ ID NO: 624)
T46984_PEA_1_node_65 (SEQ ID NO: 625)
T46984_PEA_1_node_69 (SEQ ID NO: 626)
T46984_PEA_1_node_75 (SEQ ID NO: 627)
T46984_PEA_1_node_86 (SEQ ID NO: 628)
T46984_PEA_1_node_9 (SEQ ID NO: 629)
T46984_PEA_1_node_13 (SEQ ID NO: 630)
T46984_PEA_1_node_19 (SEQ ID NO: 631)
T46984_PEA_1_node_21 (SEQ ID NO: 632)
T46984_PEA_1_node_22 (SEQ ID NO: 633)
T46984_PEA_1_node_26 (SEQ ID NO: 634)
T46984_PEA_1_node_28 (SEQ ID NO: 635)
T46984_PEA_1_node_31 (SEQ ID NO: 636)
T46984_PEA_1_node_32 (SEQ ID NO: 637)
T46984_PEA_1_node_38 (SEQ ID NO: 638)
T46984_PEA_1_node_39 (SEQ ID NO: 639)
T46984_PEA_1_node_40 (SEQ ID NO: 640)
T46984_PEA_1_node_42 (SEQ ID NO: 641)
T46984_PEA_1_node_43 (SEQ ID NO: 642)
T46984_PEA_1_node_48 (SEQ ID NO: 643)
T46984_PEA_1_node_49 (SEQ ID NO: 644)
T46984_PEA_1_node_50 (SEQ ID NO: 645)
T46984_PEA_1_node_51 (SEQ ID NO: 646)
T46984_PEA_1_node_53 (SEQ ID NO: 647)
T46984_PEA_1_node_54 (SEQ ID NO: 648)
T46984_PEA_1_node_55 (SEQ ID NO: 649)
T46984_PEA_1_node_57 (SEQ ID NO: 650)
T46984_PEA_1_node_60 (SEQ ID NO: 651)
T46984_PEA_1_node_62 (SEQ ID NO: 652)
T46984_PEA_1_node_66 (SEQ ID NO: 653)
T46984_PEA_1_node_67 (SEQ ID NO: 654)
T46984_PEA_1_node_70 (SEQ ID NO: 655)
T46984_PEA_1_node_71 (SEQ ID NO: 656)
T46984_PEA_1_node_72 (SEQ ID NO: 657)
T46984_PEA_1_node_73 (SEQ ID NO: 658)
T46984_PEA_1_node_74 (SEQ ID NO: 659)
T46984_PEA_1_node_83 (SEQ ID NO: 660)
T46984_PEA_1_node_84 (SEQ ID NO: 661)
T46984_PEA_1_node_85 (SEQ ID NO: 662)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
T46984_PEA_1_P2 (SEQ ID NO: 664)
T46984_PEA_1_P3 (SEQ ID NO: 665)
T46984_PEA_1_P10 (SEQ ID NO: 666)
T46984_PEA_1_P11 (SEQ ID NO: 667)
T46984_PEA_1_P12 (SEQ ID NO: 668)
T46984_PEA_1_P21 (SEQ ID NO: 669)
T46984_PEA_1_P27 (SEQ ID NO: 670)
T46984_PEA_1_P32 (SEQ ID NO: 671)
T46984_PEA_1_P34 (SEQ ID NO: 672)
T46984_PEA_1_P35 (SEQ ID NO: 673)
T46984_PEA_1_P38 (SEQ ID NO: 674)
T46984_PEA_1_P39 (SEQ ID NO: 675)
T46984_PEA_1_P45 (SEQ ID NO: 676)
T46984_PEA_1_P46 (SEQ ID NO: 677)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
T11628_PEA_1_T3 (SEQ ID NO: 678)
T11628_PEA_1_T4 (SEQ ID NO: 679)
T11628_PEA_1_T5 (SEQ ID NO: 680)
T11628_PEA_1_T7 (SEQ ID NO: 681)
T11628_PEA_1_T9 (SEQ ID NO: 682)
T11628_PEA_1_T11 (SEQ ID NO: 683)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
T11628_PEA_1_node_7 (SEQ ID NO: 684)
T11628_PEA_1_node_11 (SEQ ID NO: 685)
T11628_PEA_1_node_16 (SEQ ID NO: 686)
T11628_PEA_1_node_22 (SEQ ID NO: 687)
T11628_PEA_1_node_25 (SEQ ID NO: 688)
T11628_PEA_1_node_31 (SEQ ID NO: 689)
T11628_PEA_1_node_37 (SEQ ID NO: 690)
T11628_PEA_1_node_0 (SEQ ID NO: 691)
T11628_PEA_1_node_4 (SEQ ID NO: 692)
T11628_PEA_1_node_9 (SEQ ID NO: 693)
T11628_PEA_1_node_13 (SEQ ID NO: 694)
T11628_PEA_1_node_14 (SEQ ID NO: 695)
T11628_PEA_1_node_17 (SEQ ID NO: 696)
T11628_PEA_1_node_18 (SEQ ID NO: 697)
T11628_PEA_1_node_19 (SEQ ID NO: 698)
T11628_PEA_1_node_24 (SEQ ID NO: 699)
T11628_PEA_1_node_27 (SEQ ID NO: 700)
T11628_PEA_1_node_28 (SEQ ID NO: 701)
T11628_PEA_1_node_29 (SEQ ID NO: 702)
T11628_PEA_1_node_30 (SEQ ID NO: 703)
T11628_PEA_1_node_32 (SEQ ID NO: 704)
T11628_PEA_1_node_33 (SEQ ID NO: 705)
T11628_PEA_1_node_34 (SEQ ID NO: 706)
T11628_PEA_1_node_35 (SEQ ID NO: 707)
T11628_PEA_1_node_36 (SEQ ID NO: 708)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
T11628_PEA_1_P2 (SEQ ID NO: 712)
T11628_PEA_1_P5 (SEQ ID NO: 713)
T11628_PEA_1_P7 (SEQ ID NO: 714)
T11628_PEA_1_P10 (SEQ ID NO: 715)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
M78076_PEA_1_T2 (SEQ ID NO: 716)
M78076_PEA_1_T3 (SEQ ID NO: 717)
M78076_PEA_1_T5 (SEQ ID NO: 718)
M78076_PEA_1_T13 (SEQ ID NO: 719)
M78076_PEA_1_T15 (SEQ ID NO: 720)
M78076_PEA_1_T23 (SEQ ID NO: 721)
M78076_PEA_1_T26 (SEQ ID NO: 722)
M78076_PEA_1_T27 (SEQ ID NO: 723)
M78076_PEA_1_T28 (SEQ ID NO: 724)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
M78076_PEA_1_node_0 (SEQ ID NO: 725)
M78076_PEA_1_node_10 (SEQ ID NO: 726)
M78076_PEA_1_node_15 (SEQ ID NO: 727)
M78076_PEA_1_node_18 (SEQ ID NO: 728)
M78076_PEA_1_node_20 (SEQ ID NO: 729)
M78076_PEA_1_node_24 (SEQ ID NO: 730)
M78076_PEA_1_node_26 (SEQ ID NO: 731)
M78076_PEA_1_node_29 (SEQ ID NO: 732)
M78076_PEA_1_node_32 (SEQ ID NO: 733)
M78076_PEA_1_node_35 (SEQ ID NO: 734)
M78076_PEA_1_node_37 (SEQ ID NO: 735)
M78076_PEA_1_node_46 (SEQ ID NO: 736)
M78076_PEA_1_node_47 (SEQ ID NO: 737)
M78076_PEA_1_node_54 (SEQ ID NO: 738)
M78076_PEA_1_node_1 (SEQ ID NO: 739)
M78076_PEA_1_node_2 (SEQ ID NO: 740)
M78076_PEA_1_node_3 (SEQ ID NO: 741)
M78076_PEA_1_node_6 (SEQ ID NO: 742)
M78076_PEA_1_node_7 (SEQ ID NO: 743)
M78076_PEA_1_node_12 (SEQ ID NO: 744)
M78076_PEA_1_node_22 (SEQ ID NO: 745)
M78076_PEA_1_node_27 (SEQ ID NO: 746)
M78076_PEA_1_node_30 (SEQ ID NO: 747)
M78076_PEA_1_node_31 (SEQ ID NO: 748)
M78076_PEA_1_node_34 (SEQ ID NO: 749)
M78076_PEA_1_node_36 (SEQ ID NO: 750)
M78076_PEA_1_node_41 (SEQ ID NO: 751)
M78076_PEA_1_node_42 (SEQ ID NO: 752)
M78076_PEA_1_node_43 (SEQ ID NO: 753)
M78076_PEA_1_node_45 (SEQ ID NO: 754)
M78076_PEA_1_node_49 (SEQ ID NO: 755)
M78076_PEA_1_node_50 (SEQ ID NO: 756)
M78076_PEA_1_node_51 (SEQ ID NO: 757)
M78076_PEA_1_node_52 (SEQ ID NO: 758)
M78076_PEA_1_node_53 (SEQ ID NO: 759)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
M78076_PEA_1_P3 (SEQ ID NO: 761)
M78076_PEA_1_P4 (SEQ ID NO: 762)
M78076_PEA_1_P12 (SEQ ID NO: 763)
M78076_PEA_1_P14 (SEQ ID NO: 764)
M78076_PEA_1_P21 (SEQ ID NO: 765)
M78076_PEA_1_P24 (SEQ ID NO: 766)
M78076_PEA_1_P2 (SEQ ID NO: 767)
M78076_PEA_1_P25 (SEQ ID NO: 768)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name
HSMUC1A_PEA_1_T12 (SEQ ID NO:769)
HSMUC1A_PEA_1_T26 (SEQ ID NO:770)
HSMUC1A_PEA_1_T28 (SEQ ID NO:771)
HSMUC1A_PEA_1_T29 (SEQ ID NO:772)
HSMUC1A_PEA_1_T30 (SEQ ID NO:773)
HSMUC1A_PEA_1_T31 (SEQ ID NO:774)
HSMUC1A_PEA_1_T33 (SEQ ID NO:775)
HSMUC1A_PEA_1_T34 (SEQ ID NO:776)
HSMUC1A_PEA_1_T35 (SEQ ID NO:777)
HSMUC1A_PEA_1_T36 (SEQ ID NO:778)
HSMUC1A_PEA_1_T40 (SEQ ID NO:779)
HSMUC1A_PEA_1_T42 (SEQ ID NO:780)
HSMUC1A_PEA_1_T43 (SEQ ID NO:781)
HSMUC1A_PEA_1_T47 (SEQ ID NO:782)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name
HSMUC1A_PEA_1_node_0 (SEQ ID NO:783)
HSMUC1A_PEA_1_node_14 (SEQ ID NO:784)
HSMUC1A_PEA_1_node_24 (SEQ ID NO:785)
HSMUC1A_PEA_1_node_29 (SEQ ID NO:786)
HSMUC1A_PEA_1_node_35 (SEQ ID NO:787)
HSMUC1A_PEA_1_node_38 (SEQ ID NO:788)
HSMUC1A_PEA_1_node_3 (SEQ ID NO:789)
HSMUC1A_PEA_1_node_4 (SEQ ID NO:790)
HSMUC1A_PEA_1_node_5 (SEQ ID NO:791)
HSMUC1A_PEA_1_node_6 (SEQ ID NO:792)
HSMUC1A_PEA_1_node_7 (SEQ ID NO:793)
HSMUC1A_PEA_1_node_17 (SEQ ID NO:794)
HSMUC1A_PEA_1_node_18 (SEQ ID NO:795)
HSMUC1A_PEA_1_node_20 (SEQ ID NO:796)
HSMUC1A_PEA_1_node_21 (SEQ ID NO:797)
HSMUC1A_PEA_1_node_23 (SEQ ID NO:798)
HSMUC1A_PEA_1_node_26 (SEQ ID NO:799)
HSMUC1A_PEA_1_node_27 (SEQ ID NO:800)
HSMUC1A_PEA_1_node_31 (SEQ ID NO:801)
HSMUC1A_PEA_1_node_34 (SEQ ID NO:802)
HSMUC1A_PEA_1_node_36 (SEQ ID NO:803)
HSMUC1A_PEA_1_node_37 (SEQ ID NO:804)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name
HSMUC1A_PEA_1_P25 (SEQ ID NO:806)
HSMUC1A_PEA_1_P29 (SEQ ID NO:807)
HSMUC1A_PEA_1_P30 (SEQ ID NO:808)
HSMUC1A_PEA_1_P32 (SEQ ID NO:809)
HSMUC1A_PEA_1_P36 (SEQ ID NO:810)
HSMUC1A_PEA_1_P39 (SEQ ID NO:811)
HSMUC1A_PEA_1_P45 (SEQ ID NO:812)
HSMUC1A_PEA_1_P49 (SEQ ID NO:813)
HSMUC1A_PEA_1_P52 (SEQ ID NO:814)
HSMUC1A_PEA_1_P53 (SEQ ID NO:815)
HSMUC1A_PEA_1_P56 (SEQ ID NO:816)
HSMUC1A_PEA_1_P58 (SEQ ID NO:817)
HSMUC1A_PEA_1_P59 (SEQ ID NO:818)
HSMUC1A_PEA_1_P63 (SEQ ID NO:819)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSMUC1A_PEA—1_P63 (SEQ ID NO:819), comprising a first amino acid sequence being at least 90% homologous to MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSV corresponding to amino acids 1-45 of MUC1_HUMAN (SEQ ID NO:805), which also corresponds to amino acids 1-45 of HSMUC1A_PEA—1_P63 (SEQ ID NO:819), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK (SEQ ID NO:946) corresponding to amino acids 46-85 of HSMUC1A_PEA—1_P63 (SEQ ID NO:819), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSMUC1A_PEA—1_P63 (SEQ ID NO:819), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK (SEQ ID NO:946) in HSMUC1A_PEA—1_P63 (SEQ ID NO:819).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P2 (SEQ ID NO:664), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1-498 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-498 of T46984_PEA—1_P2 (SEQ ID NO:664), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VCA corresponding to amino acids 499-501 of T46984_PEA—1_P2 (SEQ ID NO:664), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P3 (SEQ ID NO:665), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQ corresponding to amino acids 1-433 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-433 of T46984_PEA—1_P3 (SEQ ID NO:665), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ICHIWKLIFLP (SEQ ID NO:947) corresponding to amino acids 434-444 of T46984_PEA—1_P3 (SEQ ID NO:665), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P3 (SEQ ID NO:665), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ICHIWKLIFLP (SEQ ID NO:947) in T46984_PEA—1_P3 (SEQ ID NO:665).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P10 (SEQ ID NO:666), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1-498 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-498 of T46984_PEA—1_P10 (SEQ ID NO:666), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LMDQK (SEQ ID NO:948) corresponding to amino acids 499-503 of T46984_PEA—1_P10 (SEQ ID NO:666), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P10 (SEQ ID NO:666), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LMDQK (SEQ ID NO:948) in T46984_PEA—1_P10 (SEQ ID NO:666).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P11 (SEQ ID NO:667), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEK RPPTVVSNTFTALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWT QLNMFQTLKYLAILGSVTFLAGNRMLAQQAVKR corresponding to amino acids 1-628 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-628 of T46984_PEA—1_P11 (SEQ ID NO:667).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P12 (SEQ ID NO:668), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMN corresponding to amino acids 1-338 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-338 of T46984_PEA—1_P12 (SEQ ID NO:668), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SQDLH (SEQ ID NO:949) corresponding to amino acids 339-343 of T46984_PEA—1_P12 (SEQ ID NO:668), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P12 (SEQ ID NO:668), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SQDLH (SEQ ID NO:949) in T46984_PEA—1_P12 (SEQ ID NO:668).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P21 (SEQ ID NO:669), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence M corresponding to amino acids 1-1 of T46984_PEA—1_P21 (SEQ ID NO:669), and a second amino acid sequence being at least 90% homologous to KACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSSVTQIYHAV AALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVA RLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFES LSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPLTQATVKL EHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIANTVEL RVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQLVDVNT GAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDSASGTYTLYLII GDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEKRPPTVVSNTF TALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWTQLNMFQTLKY LAILGSVTFLAGNRMLAQQAVKRTAH corresponding to amino acids 70-631 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 2-563 of T46984_PEA—1_P21 (SEQ ID NO:669), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P27 (SEQ ID NO:670), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFA corresponding to amino acids 1-415 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-415 of T46984_PEA—1P27 (SEQ ID NO:670), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP (SEQ ID NO:950) corresponding to amino acids 416-459 of T46984_PEA—1_P27 (SEQ ID NO:670), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P27 (SEQ ID NO:670), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP (SEQ ID NO:950) in T46984_PEA—1_P27 (SEQ ID NO:670).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P32 (SEQ ID NO:671), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVE corresponding to amino acids 1-364 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-364 of T46984_PEA—1_P32 (SEQ ID NO:671), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT (SEQ ID NO:951) corresponding to amino acids 365-397 of T46984_PEA—1_P32 (SEQ ID NO:671), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P32 (SEQ ID NO:671), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT (SEQ ID NO:951) in T46984_PEA—1_P32 (SEQ ID NO:671).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P34 (SEQ ID NO:672), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVG corresponding to amino acids 1-329 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-329 of T46984_PEA—113 P34 (SEQ ID NO:672).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P35 (SEQ ID NO:673), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAI corresponding to amino acids 1-287 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-287 of T46984_PEA—1_P35 (SEQ ID NO:673), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI (SEQ ID NO:952) corresponding to amino acids 288-334 of T46984_PEA—1_P35 (SEQ ID NO:673), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P35 (SEQ ID NO:673), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI (SEQ ID NO:952) in T46984_PEA—1_P35 (SEQ ID NO:673).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P38 (SEQ ID NO:674), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEAL corresponding to amino acids 1-145 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-145 of T46984_PEA—1_P38 (SEQ ID NO:674), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDPDWCQCLQLHFCS (SEQ ID NO:953) corresponding to amino acids 146-160 of T46984_PEA—1_P38 (SEQ ID NO:674), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P38 (SEQ ID NO:674), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDPDWCQCLQLHFCS (SEQ ID NO:953) in T46984_PEA—1_P38 (SEQ ID NO:674)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P39 (SEQ ID NO:675), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLA corresponding to amino acids 1-160 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-160 of T46984_PEA—1_P39 (SEQ ID NO:675).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P45 (SEQ ID NO:676), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCE corresponding to amino acids 1-101 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-101 of T46984_PEA—1_P45 (SEQ ID NO:676), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) corresponding to amino acids 102-116 of T46984_PEA—1_P45 (SEQ ID NO:676), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P45 (SEQ ID NO:676), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) in T46984_PEA—1_P45 (SEQ ID NO:676).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA—1_P46 (SEQ ID NO:677), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAK corresponding to amino acids 1-69 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-69 of T46984_PEA—1_P46 (SEQ ID NO:677), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) corresponding to amino acids 70-84 of T46984_PEA—1_P46 (SEQ ID NO:677), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA—1_P46 (SEQ ID NO:677), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) in T46984_PEA—1_P46 (SEQ ID NO:677).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA—1_P2 (SEQ ID NO:712), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) corresponding to amino acids 1-55 of T11628_PEA—1_P2 (SEQ ID NO:712), and a second amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of Q8WVH6 (SEQ ID NO:711), which also corresponds to amino acids 56-154 of T11628_PEA—1_P2 (SEQ ID NO:712), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T11628_PEA—1_P2 (SEQ ID NO:712), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956)
of T11628_PEA_1_P2. (SEQ ID NO:712)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA—1_P5 (SEQ ID NO:713), comprising a first amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 56-154 of MYG_HUMAN_V1 (SEQ ID NO:710), which also corresponds to amino acids 1-99 of T11628_PEA—1_P5 (SEQ ID NO:713).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA—1_P7 (SEQ ID NO:714), comprising a first amino acid sequence being at least 90% homologous to MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMK ASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQ SKHPGDFGADAQGAMNK corresponding to amino acids 1-134 of MYG_HUMAN_V1 (SEQ ID NO:710), which also corresponds to amino acids 1-134 of T11628_PEA—1_P7 (SEQ ID NO:714) and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence G corresponding to amino acids 135-135 of T11628_PEA—1_P7 (SEQ ID NO:714), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA—1_P10 (SEQ ID NO:715), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) corresponding to amino acids 1-55 of T111628_PEA—1_P10 (SEQ ID NO:715), and a second amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of Q8WVH6 (SEQ ID NO:711), which also corresponds to amino acids 56-154 of T11628_PEA—1_P10 (SEQ ID NO:715), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T11628_PEA—1_P10 (SEQ ID NO:715), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) of T11628_PEA—1_P10 (SEQ ID NO:715).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P3 (SEQ ID NO:761), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKD corresponding to amino acids 1-517 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-517 of M78076_PEA—1_P3 (SEQ ID NO:761), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GE corresponding to amino acids 518-519 of M78076_PEA—1_P3 (SEQ ID NO:761), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P4 (SEQ ID NO:762), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1-526 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-526 of M78076_PEA—1_P4 (SEQ ID NO:762), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECLTVNPSLQIPLNP (SEQ ID NO:958) corresponding to amino acids 527-541 of M78076_PEA—1_P4 (SEQ ID NO:762), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA—1_P4 (SEQ ID NO:762), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECLTVNPSLQIPLNP (SEQ ID NO:958) in M78076_PEA—1_P4 (SEQ ID NO:762).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P12 (SEQ ID NO:763), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1-526 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-526 of M78076_PEA—1_P12 (SEQ ID NO:763), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO:959) corresponding to amino acids 527-544 of M78076_PEA—1_P12 (SEQ ID NO:763), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA—1_P12 (SEQ ID NO:763), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO:959) in M78076_PEA—1_P12 (SEQ ID NO:763).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P14 (SEQ ID NO:764), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGST EQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDEL corresponding to amino acids 1-570 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-570 of M78076_PEA—1_P14 (SEQ ID NO:764), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO:960) corresponding to amino acids 571-619 of M78076_PEA—1_P14 (SEQ ID NO:764), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA—1_P14 (SEQ ID NO:764), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO:960) in M78076_PEA—1_P14 (SEQ ID NO:764).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P21 (SEQ ID NO:765), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN E corresponding to amino acids 1-352 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-352 of M78076_PEA—1_P21 (SEQ ID NO:765), and a second amino acid sequence being at least 90% homologous to AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQ SLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMT LPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDELAPAGTGVSREA VSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYE NPTYRFLEERP corresponding to amino acids 406-650 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 353-597 of M78076_PEA—1_P21 (SEQ ID NO:765), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of M78076_PEA—1_P21 (SEQ ID NO:765), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EA, having a structure as follows: a sequence starting from any of amino acid numbers 352-x to 352; and ending at any of amino acid numbers 353+((n−2)−x), in which x varies from 0 to n-2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P24 (SEQ ID NO:766), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQI corresponding to amino acids 1-481 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-481 of M78076_PEA—1_P24 (SEQ ID NO:766), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RECLLPWLPLQISEGRS (SEQ ID NO:961) corresponding to amino acids 482-498 of M78076_PEA—1_P24 (SEQ ID NO:766), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA—1_P24 (SEQ ID NO:766), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RECLLPWLPLQISEGRS (SEQ ID NO:961) in M78076_PEA—1_P24 (SEQ ID NO:766).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P2 (SEQ ID NO:767), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQV corresponding to amino acids 1-449 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-449 of M78076_PEA—1_P2 (SEQ ID NO:767), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT STSWVQAILLPQPLE (SEQ ID NO:962) corresponding to amino acids 450-588 of M78076_PEA—1_P2 (SEQ ID NO:767), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA—1_P2 (SEQ ID NO:767), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT (SEQ ID NO:962)
CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT
STSWVQAILLPQPLE
in M78076_PEA_1_P2. (SEQ ID NO:767)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA—1_P25 (SEQ ID NO:768), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQ corresponding to amino acids 1-448 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-448 of M78076_PEA—1_P25 (SEQ ID NO:768), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID NO:963) corresponding to amino acids 449-505 of M78076_PEA—1_P25 (SEQ ID NO:768), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA—1_P25 (SEQ ID NO:768), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID NO:963) in M78076_PEA—1_P25 (SEQ ID NO:768).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M85491_PEA—1_P13 (SEQ ID NO:246), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN SRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSG GREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAV NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL QYYEK corresponding to amino acids 1-476 of EPB2_HUMAN (SEQ ID NO:245), which also corresponds to amino acids 1-476 of M85491_PEA—1_P13 (SEQ ID NO:246), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:964) corresponding to amino acids 477-496 of M85491_PEA—1_P13 (SEQ ID NO:246), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M85491_PEA—1_P13 (SEQ ID NO:246), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:964) in M85491_PEA—1_P13 (SEQ ID NO:246).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M85491_PEA—1_P14 (SEQ ID NO:247), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:245), which also corresponds to amino acids 1-270 of M85491_PEA—1_P14 (SEQ ID NO:247), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:965) corresponding to amino acids 271-301 of M85491_PEA—1_P14 (SEQ ID NO:247), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M85491_PEA—1_P14 (SEQ ID NO:247), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:965) in M85491_PEA—1_P14 (SEQ ID NO:247).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P4 (SEQ ID NO:271), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P4 (SEQ ID NO:271), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4 (SEQ ID NO:271), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPE KNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG corresponding to amino acids 165-445 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-445 of HSSTROL3_P4 (SEQ ID NO:271), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:966) corresponding to amino acids 446-496 of HSSTROL3_P4 (SEQ ID NO:271), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P4 (SEQ ID NO:271), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:966) in HSSTROL3_P4 (SEQ ID NO:271).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P5 (SEQ ID NO:272), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P5 (SEQ ID NO:272), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5 (SEQ ID NO:272), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQ corresponding to amino acids 165-358 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-358 of HSSTROL3_P5 (SEQ ID NO:272), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:967) corresponding to amino acids 359-382 of HSSTROL3_P5 (SEQ ID NO:272), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P5 (SEQ ID NO:272), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:967) in HSSTROL3_P5 (SEQ ID NO:272).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P7 (SEQ ID NO:273), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P7 (SEQ ID NO:273), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7 (SEQ ID NO:273), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-359 of HSSTROL3_P7 (SEQ ID NO:273), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:968) corresponding to amino acids 360-370 of HSSTROL3_P7 (SEQ ID NO:273), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P7 (SEQ ID NO:273), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:968) in HSSTROL3_P7 (SEQ ID NO:273).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P8 (SEQ ID NO:274), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P8 (SEQ ID NO:274), a bridging amino acid H corresponding to amino acid 164of HSSTROL3_P8 (SEQ ID NO:274), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLE corresponding to amino acids 165-286 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-286 of HSSTROL3_P8 (SEQ ID NO:274), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRPCLPVPLLLCWPL (SEQ ID NO:969) corresponding to amino acids 287-301 of HSSTROL3_P8 (SEQ ID NO:274), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P8 (SEQ ID NO:274), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRPCLPVPLLLCWPL (SEQ ID NO:969) in HSSTROL3_P8 (SEQ ID NO:274).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P9 (SEQ ID NO:275), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1-96 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-96 of HSSTROL3_P9 (SEQ ID NO:275), a second amino acid sequence being at least 90% homologous to RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 113-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 97-147 of HSSTROL3_P9 (SEQ ID NO:275), a bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9 (SEQ ID NO:275), a third amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 149-343 of HSSTROL3_P9 (SEQ ID NO:275), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:968) corresponding to amino acids 344-354 of HSSTROL3_P9 (SEQ ID NO:275), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HSSTROL3_P9 (SEQ ID NO:275), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96-x to 96; and ending at any of amino acid numbers 97+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P9 (SEQ ID NO:275), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:968) in HSSTROL3_P9 (SEQ ID NO:275).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AY180924_PEA—1_P3 (SEQ ID NO:281), comprising a first amino acid sequence being at least 90% homologous to MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN corresponding to amino acids 1-33 of LATH_HUMAN (SEQ ID NO:280), which also corresponds to amino acids 1-33 of AY180924_PEA—1_P3 (SEQ ID NO:281), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY (SEQ ID NO:971) corresponding to amino acids 34-64 of AY180924_PEA—1_P3 (SEQ ID NO:281), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of AY180924_PEA—1_P3 (SEQ ID NO:281), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY (SEQ ID NO:971) in AY180924_PEA—1_P3 (SEQ ID NO:281).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R75793_PEA—1_P2 (SEQ ID NO:295), comprising a first amino acid sequence being at least 90% homologous to MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAATTATTAAPT TATTAASTTARKDIP corresponding to amino acids 1-74 of Q96DR8 (SEQ ID NO:294), which also corresponds to amino acids 1-74 of R75793_PEA—1_P2 (SEQ ID NO:295), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AP corresponding to amino acids 75-76 of R75793_PEA—1_P2 (SEQ ID NO:295), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P14 (SEQ ID NO:350), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVK GADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPT GDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPR GQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGP PGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQG LPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP V corresponding to amino acids 1-1056 of CA1B_HUMAN_V5 (SEQ ID NO:349), which also corresponds to amino acids 1-1056 of HUMCA1XIA_P14 (SEQ ID NO:350), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:972) corresponding to amino acids 1057-1081 of HUMCA1XIA_P14 (SEQ ID NO:350), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P14 (SEQ ID NO:350), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:972) in HUMCA1XIA_P14 (SEQ ID NO:350).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P15 (SEQ ID NO:351 ), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEK corresponding to amino acids 1-714 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-714 of HUMCA1XIA_P15 (SEQ ID NO:351), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCCNLSFGILIPLQK (SEQ ID NO:973) corresponding to amino acids 715-729 of HUMCA1XIA_P15 (SEQ ID NO:351), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P15 (SEQ ID NO :351 ), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK (SEQ ID NO:973) in HUMCA1XIA_P15 (SEQ ID NO:351).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P16 (SEQ ID NO:352), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA corresponding to amino acids 1-648 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-648 of HUMCA1XIA_P16 (SEQ ID NO:352), a second amino acid sequence being at least 90% homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667-714 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID NO:352), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:974) corresponding to amino acids 697-738 of HUMCA1XIA_P16 (SEQ ID NO:352), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCA1XIA_P16 (SEQ ID NO:352), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and ending at any of amino acid numbers 649+((n−2)−x), in which x varies from 0 to n-2.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P16 (SEQ ID NO:352), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:974) in HUMCA1XIA_P16 (SEQ ID NO:352).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P17 (SEQ ID NO:353), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids 1-260 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-260 of HUMCA1XIA_P17 (SEQ ID NO:353), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSTRPEKVFVFQ (SEQ ID NO:975) corresponding to amino acids 261-273 of HUMCA1XIA_P17 (SEQ ID NO:353), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P17 (SEQ ID NO:353), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSTRPEKVFVFQ (SEQ ID NO:975) in HUMCA1XIA_P17 (SEQ ID NO:353).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R20779_P2 (SEQ ID NO:380), comprising a first amino acid sequence being at least 90% homologous to MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLV NAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRH RFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids 1-169 of STC2_HUMAN (SEQ ID NO:379), which also corresponds to amino acids 1-169 of R20779_P2 (SEQ ID NO:380), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:976) corresponding to amino acids 170-187 of R20779_P2 (SEQ ID NO:380), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R20779_P2 (SEQ ID NO:380), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:976) in R20779_P2 (SEQ ID NO:380).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P3 (SEQ ID NO:488), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTV corresponding to amino acids 1-865 of CO4_HUMAN, which also corresponds to amino acids 1-865 of HSCOC4_PEA—1_P3 (SEQ ID NO:488), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RPHRSLSIQELGEPGPSEGWGG (SEQ ID NO:977) corresponding to amino acids 866-887 of HSCOC4_PEA—1_P3 (SEQ ID NO:488), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P3 (SEQ ID NO:488), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RPHRSLSIQELGEPGPSEGWGG (SEQ ID NO:977) in HSCOC4_PEA—1_P3 (SEQ ID NO:488).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P5 (SEQ ID NO:489), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids 1-818 of CO4_HUMAN, which also corresponds to amino acids 1-818 of HSCOC4_PEA—1_P5 (SEQ ID NO:489), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) corresponding to amino acids 819-843 of HSCOC4_PEA—1_P5 (SEQ ID NO:489), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P5 (SEQ ID NO:489), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) in HSCOC4_PEA—1_P5 (SEQ ID NO:489).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P6 (SEQ ID NO:490), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKG corresponding to amino acids 1-1052 of CO4_HUMAN, which also corresponds to amino acids 1-1052 of HSCOC4_PEA—1_P6 (SEQ ID NO:490), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP (SEQ ID NO:979) corresponding to amino acids 1053-1084 of HSCOC4_PEA—1_P6 (SEQ ID NO:490), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P6 (SEQ ID NO:490), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP (SEQ ID NO:979) in HSCOC4_PEA—1_P6 (SEQ ID NO:490).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P12 (SEQ ID NO:491), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKV corresponding to amino acids 1-1380 of CO4_HUMAN_V1(SEQ ID NO:486), which also corresponds to amino acids 1-1380 of HSCOC4_PEA—1_P12 (SEQ ID NO:491), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RAREGVGPGTGGGEGVE (SEQ ID NO:980) corresponding to amino acids 1381-1397 of HSCOC4_PEA—1_P12 (SEQ ID NO:491), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P12 (SEQ ID NO:491), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RAREGVGPGTGGGEGVE (SEQ ID NO:980) in HSCOC4_PEA—1_P12 (SEQ ID NO:491).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P15 (SEQ ID NO:492), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQ corresponding to amino acids 1-1359 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1359 of HSCOC4_PEA—1_P15 (SEQ ID NO:492), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL (SEQ ID NO:981) corresponding to amino acids 1360-1415 of HSCOC4_PEA—1_P15 (SEQ ID NO:492), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P15 (SEQ ID NO:492), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL (SEQ ID NO:981) in HSCOC4_PEA—1_P15 (SEQ ID NO:492).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P16 (SEQ ID NO:493), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPK corresponding to amino acids 1-1457 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1457 of HSCOC4_PEA—1_P16 (SEQ ID NO:493), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AERQGGAVWHGHRGRHPPEWIPRPAC (SEQ ID NO:982) corresponding to amino acids 1458-1483 of HSCOC4_PEA—1_P16 (SEQ ID NO:493), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P16 (SEQ ID NO:493), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AERQGGAVWHGHRGRHPPEWIPRPAC (SEQ ID NO:982) in HSCOC4_PEA—1_P16 (SEQ ID NO:493).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P20 (SEQ ID NO:494), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQ corresponding to amino acids 1-1303 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1303 of HSCOC4_PEA—1_P20 (SEQ ID NO:494), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH (SEQ ID NO:983) corresponding to amino acids 1304-1349 of HSCOC4_PEA—1_P20 (SEQ ID NO:494), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P20 (SEQ ID NO:494), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO: 983)
VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH
(SEQ ID NO: 494)
in HSCOC4_PEA_1_P20.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P9 (SEQ ID NO:495), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1-1529 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1529 of HSCOC4_PEA—1_P9 (SEQ ID NO:495), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER (SEQ ID NO:984) corresponding to amino acids 1530-1533 of HSCOC4_PEA—1_P9 (SEQ ID NO:495), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P9 (SEQ ID NO:495), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER (SEQ ID NO:984) in HSCOC4_PEA—1_P9 (SEQ ID NO:495).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P22 (SEQ ID NO:496), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAF RLFETKITQVLHF corresponding to amino acids 1-1653 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1653 of HSCOC4_PEA—1_P22 (SEQ ID NO:496), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SMKQTGEAGRAGGRQGG (SEQ ID NO:985) corresponding to amino acids 1654-1670 of HSCOC4_PEA—1_P22 (SEQ ID NO:496), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P22 (SEQ ID NO:496), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SMKQTGEAGRAGGRQGG (SEQ ID NO:985) in HSCOC4_PEA—1_P22 (SEQ ID NO:496).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P23 (SEQ ID NO:497), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYG corresponding to amino acids 1-1626 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1626 of HSCOC4_PEA—1_P23 (SEQ ID NO:497), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS (SEQ ID NO:986) corresponding to amino acids 1627-1685 of HSCOC4_PEA—1_P23 (SEQ ID NO:497), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P23 (SEQ ID NO:497), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS (SEQ ID NO:986) in HSCOC4_PEA—1_P23 (SEQ ID NO:497).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P24 (SEQ ID NO:498), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDS corresponding to amino acids 1-1528 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1528 of HSCOC4_PEA—1_P24 (SEQ ID NO:498), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG (SEQ ID NO:987) corresponding to amino acids 1529-1579 of HSCOC4_PEA—1_P24 (SEQ ID NO:498), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P24 (SEQ ID NO:498), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG (SEQ ID NO: 987)
in HSCOC4_PEA_1_P24. (SEQ ID NO: 498)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P25 (SEQ ID NO:499), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1-1593 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1593 of HSCOC4_PEA—1_P25 (SEQ ID NO:499), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG (SEQ ID NO:988) corresponding to amino acids 1594-1657 of HSCOC4_PEA—1_P25 (SEQ ID NO:499), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P25 (SEQ ID NO:499), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC (SEQ ID NO: 988)
GVRLPG
in HSCOC4_PEA_1_P25. (SEQ ID NO: 499)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P26 (SEQ ID NO:500), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1-1593 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1593 of HSCOC4_PEA—1_P26 (SEQ ID NO:500), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC (SEQ ID NO: 989)
GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL

corresponding to amino acids 1594-1691 of HSCOC4_PEA—1_P26 (SEQ ID NO:500), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P26 (SEQ ID NO:500), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC (SEQ ID NO: 989)
GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL
in HSCOC4_PEA_1_P26. (SEQ ID NO: 500)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P30 (SEQ ID NO:501), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGS corresponding to amino acids 1-1232 of CO4_HUMAN_V3 (SEQ ID NO:487), which also corresponds to amino acids 1-1232 of HSCOC4_PEA—1_P30 (SEQ ID NO:501), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RNPVRLLQPRAQMFCVLRGTK (SEQ ID NO:990) corresponding to amino acids 1233-1253 of HSCOC4_PEA—1_P30 (SEQ ID NO:501), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P30 (SEQ ID NO:501), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RNPVRLLQPRAQMFCVLRGTK (SEQ ID NO:990) in HSCOC4_PEA—1_P30 (SEQ ID NO:501).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P38 (SEQ ID NO:502), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids 1-818 of CO4_HUMAN, which also corresponds to amino acids 1-818 of HSCOC4_PEA—1_P38 (SEQ ID NO:502), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) corresponding to amino acids 819-843 of HSCOC4_PEA—1_P38 (SEQ ID NO:502), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P38 (SEQ ID NO:502), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) in HSCOC4_PEA—1_P38 (SEQ ID NO:502).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P39 (SEQ ID NO:503), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ corresponding to amino acids 1-387 of CO4_HUMAN, which also corresponds to amino acids 1-387 of HSCOC4_PEA—1_P39 (SEQ ID NO:503), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSSRGEG (SEQ ID NO:992) corresponding to amino acids 388-394 of HSCOC4_PEA—1_P39 (SEQ ID NO:503), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P39 (SEQ ID NO:503), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSSRGEG (SEQ ID NO:992) in HSCOC4_PEA—1_P39 (SEQ ID NO:503).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P40 (SEQ ID NO:504), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY corresponding to amino acids 1-236 of CO4_HUMAN, which also corresponds to amino acids 1-236 of HSCOC4_PEA—1_P40 (SEQ ID NO:504), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY (SEQ ID NO:993) corresponding to amino acids 237-263 of HSCOC4_PEA—1_P40 (SEQ ID NO:504), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P40 (SEQ ID NO:504), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY (SEQ ID NO:993) in HSCOC4_PEA—1_P40 (SEQ ID NO:504).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P41 (SEQ ID NO:505), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1-1529 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1529 of HSCOC4_PEA—1_P41 (SEQ ID NO:505), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER (SEQ ID NO:984) corresponding to amino acids 1530-1533 of HSCOC4_PEA—1_P41 (SEQ ID NO:505), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1—l P41 (SEQ ID NO:505), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER (SEQ ID NO:984) in HSCOC4_PEA—1_P41 (SEQ ID NO:505).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P42 (SEQ ID NO:506), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIW corresponding to amino acids 1-1473 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1473 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR (SEQ ID NO:1021) corresponding to amino acids 1474-1511 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), a third amino acid sequence being at least 90% homologous to RNGKVGLSGMAIADVTLLSGFHALRADLEK corresponding to amino acids 1474-1503 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1512-1541 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWSATQGNPLCPRY (SEQ ID NO:995) corresponding to amino acids 1542-1555 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of HSCOC4_PEA—1_P42 (SEQ ID NO:506), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR (SEQ ID NO: 1021), corresponding to HSCOC4_PEA—1_P42 (SEQ ID NO:506).

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P42 (SEQ ID NO:506), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWSATQGNPLCPRY (SEQ ID NO:995) in HSCOC4_PEA—1_P42 (SEQ ID NO:506).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), comprising a first amino acid sequence being at least 90% homologous to MAARALCMLGLVLALLSSSSAEEYVGL corresponding to amino acids 1-27 of TFF3_HUMAN (SEQ ID NO:516), which also corresponds to amino acids 1-27 of HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WKVHLPKGEGFSSG (SEQ ID NO:996) corresponding to amino acids 28-41 of HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WKVHLPKGEGFSSG (SEQ ID NO:996) in HUMTREFAC_PEA—2_P8 (SEQ ID NO:518).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), comprising a first amino acid sequence being at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ corresponding to amino acids 1-58 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-58 of HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VFLNFS (SEQ ID NO:997) corresponding to amino acids 59-64 of HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VFLNFS (SEQ ID NO:997) in HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-31 of HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence H corresponding to amino acids 32-32 of HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-31 of HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSIFYVFI (SEQ ID NO:998)corresponding to amino acids 32-39 of HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSIFYVFI (SEQ ID NO:998)in HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA—1_P2 (SEQ ID NO:14), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1-319 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-319 of T10888_PEA—1_P2 (SEQ ID NO:14), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP (SEQ ID NO:999)corresponding to amino acids 320-324 of T10888_PEA—1_P2 (SEQ ID NO:14), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA—1_P2 (SEQ ID NO:14), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP (SEQ ID NO:999)in T10888_PEA—1_P2 (SEQ ID NO:14).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA.—1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-234 of T10888_PEA—1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)corresponding to amino acids 235-256 of T10888_PEA—1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA—1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)in T10888_PEA—1_P4 (SEQ ID NO:15).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA—1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of Q13774, which also corresponds to amino acids 1-234 of T10888_PEA—1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)corresponding to amino acids 235-256 of T10888_PEA—1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA—1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)in T10888_PEA—1_P4 (SEQ ID NO:15).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA—1_P5 (SEQ ID NO:16), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1-320 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-320 of T10888_PEA—1_P5 (SEQ ID NO:16), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV (SEQ ID NO:1001)corresponding to amino acids 321-390 of T10888_PEA—1_P5 (SEQ ID NO:16), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA—1_P5 (SEQ ID NO:16), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF (SEQ ID NO: 1001)
VVFCFLISHV
in T10888_PEA_1_P5. (SEQ ID NO: 16)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA—1_P6 (SEQ ID NO:17), comprising a first amino acid sequence being at least 90% homologous to

    MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLA
HNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQ
NDTGFYTLQVIKSDLVNEEATGQFHVY

corresponding to amino acids 1-141 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-141 of T10888_PEA131_P6 (SEQ ID NO:17), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

(SEQ ID NO: 1002)
REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI

corresponding to amino acids 142-183 of T10888_PEA—1_P6 (SEQ ID NO:17), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA—1_P6 (SEQ ID NO:17), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI (SEQ ID NO:1002) in T10888_PEA—1_P6 (SEQ IDNO:17.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P6 (SEQ ID NO:51), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids 1-276 of VTNC_HUMAN, which also corresponds to amino acids 1-276 of T39971_P6 (SEQ ID NO:51), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQGVVGD (SEQ ID NO:1003) corresponding to amino acids 277-283 of T39971_P6 (SEQ ID NO:51), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P6 (SEQ ID NO:51), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TQGVVGD (SEQ ID NO:1003) in T39971_P6 (SEQ ID NO:51).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P9 (SEQ ID NO:52), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids 1-325 of VTNC_HUMAN, which also corresponds to amino acids 1-325 of T39971_P9 (SEQ ID NO:52), and a second amino acid sequence being at least 90% homologous to SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGA NNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGC PAPGHL corresponding to amino acids 357-478 of VTNC_HUMAN, which also corresponds to amino acids 326-447 of T39971_P9 (SEQ ID NO:52), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971_P9 (SEQ ID NO:52) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of VTNC_HUMAN, which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of VTNC_HUMAN, which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of Q9BSH7, which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of Q9BSH7, which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of VTNC_HUMAN, which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEO ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54 , wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54) According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of Q9BSH7, which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P2 (SEO ID NO:97), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGK LRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQ GTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQ ASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYI DKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKE AAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWN corresponding to amino acids 1-761 of SUL1_HUMAN, which also corresponds to amino acids 1-761 of Z21368_PEA—1_P2 (SEQ ID NO:97), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) corresponding to amino acids 762-790 of Z21368_PEA—1_P2 (SEQ ID NO:97), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA—1_P2 (SEQ ID NO:97), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) in Z21368_PEA—1_P2 (SEQ ID NO:97).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-57 of Z21368_PEA—1_P5 (SEQ ID NO:98), second bridging amino acid sequence comprising A, and a third amino acid sequence being at least 90% homologous to FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITN ESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNM DKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYT ADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDT PPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHL PKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFE GEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT TVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKR RKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKER KEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNE THNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCN PRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 139-871 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 59-791 of Z21368_PEA—1_P5 (SEQ ID NO:98), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise LAF having a structure as follows (numbering according to Z21368_PEA—1_P5 (SEQ ID NO:98) ): a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 59+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME (SEQ ID NO:1006) corresponding to amino acids 1-751 of Z21368_PEA—1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 1-40 of AAH12997 (SEQ ID NO:841), which also corresponds to amino acids 752-791 of Z21368_PEA—1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF (SEQ ID NO: 1006)
GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES
INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK
HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD
HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP
DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP
KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA
RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE
IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV
RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK
PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE
KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH
NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME
of Z21368_PEA_1_P5. (SEQ ID NO: 98)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of SUL1_HUMAN, which also corresponds to amino acids 1-57 of Z21368_PEA—1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLIT NESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPN MDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGL DTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSN HLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVE FEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGP PTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHL KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRK KERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRT VNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYK QCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 138-871 of SUL1_HUMAN, which also corresponds to amino acids 58-791 of Z21368_PEA—1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise LA, having a structure as follows: a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 58+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P15 (SEQ ID NO:99), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERG corresponding to amino acids 1-416 of SUL1_HUMAN, which also corresponds to amino acids 1-416 of Z21368_PEA—1_P15 (SEQ ID NO:99).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P16 (SEQ ID NO:100), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to amino acids 1-397 of SUL1_HUMAN, which also corresponds to amino acids 1-397 of Z21368_PEA—1_P16 (SEQ ID NO:100), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) corresponding to amino acids 398-410 of Z21368_PEA—1_P16 (SEQ ID NO:100), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA—1_P16 (SEQ ID NO:100), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) in Z21368_PEA—1-P16 (SEQ ID NO:100).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P22 (SEQ ID NO:101), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAK corresponding to amino acids 1-188 of SUL1_HUMAN, which also corresponds to amino acids 1-188 of Z21368_PEA—1_P22 (SEQ ID NO:101), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) corresponding to amino acids 189-210 of Z21368_PEA—1_P22 (SEQ ID NO:101), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA—1_P22 (SEQ ID NO:101), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably, at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) in Z21368_PEA—1P22 (SEQ ID NO:101) .

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-137 of Z21368_PEA—1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368_PEA—1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA—1_P23 (SEQ ID NO:102).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA—1_P23 (SEB ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of SUL1_HUMAN, which also corresponds to amino acids 1-137 of Z21368_PEA—1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368 PEA—1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA—1_P23 (SEQ ID NO:102).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P5 (SEO ID NO:143), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P5 (SEQ ID NO:143), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG (SEQ ID NO:1010) corresponding to amino acids 45-189 of T59832_P5 (SEQ ID NO:143), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P5 (SEQ ID NO:143), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP (SEQ ID NO: 1010)
SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL
AATLDAFIPARAGLACLWDLLGRCPRG
in T59832_P5. (SEQ ID NO: 143)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 12-223 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011 ) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 1-148 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012)
PLVNVTLYYEALCGGCRAFLIRELFPTWLLV
of T59832_P7. (SEQ ID NO: 144)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 12-214 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEO ID NO:145).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832 P9 (SEO ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P9 (SEQ ID NO:145), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-113 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-203 of T59832_P9 (SEQ ID NO:145), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012)
PLVNVTLYYEALCGGCRAFLIRELFPTWLLV
of T59832_P9. (SEQ ID NO: 145)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

(SEQ ID NO: 1013)
NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR

corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEO ID NO:145).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 12-141 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P12 (SEQ ID NO:146), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE corresponding to amino acids 1-40 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-130 of T59832_P12 (SEQ ID NO:146), third amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 72-122 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 131-181 of T59832_P 12 (SEQ ID NO:146), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK (SEQ ID NO:1016) corresponding to amino acids 182-219 of T59832_P12 (SEQ ID NO:146), wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T59832_P12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012)
PLVNVTLYYEALCGGCRAFLIRELFPTWLLV
of T59832_P12. (SEQ ID NO: 146)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P 12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPS STS SLRSVCFK (SEO ID NO:1016) in T59832_P12 (SEQ IDNO:146).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 1-130 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_PI18 (SEQ ID NO:147), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMGRP5E-P4 (SEQ ID NO:1566), comprising a first amino acid sequence being at least 90% homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1-127 of GRP_HUMAN, which also corresponds to amino acids 1-127 of HUMGRP5E_P4 (SEQ ID NO:156), and a second amino acid sequence being at least 90% homologous to GSQREGRNPQLNQQ corresponding to amino acids 135-148 of GRP_HUMAN, which also corresponds to amino acids 128-141 of HUMGRP5E_P4 (SEQ ID NO:156), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMGRP5E_P4 (SEQ ID NO:156), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KG, having a structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino acid numbers 128 +((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMGRP5E_P5 (SEQ ID NO:157), comprising a first amino acid sequence being at least 90% homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1-127 of GRP_HUMAN, which also corresponds to amino acids 1-127 of HUMGRP5E_P5 (SEQ ID NO:157), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DSLLQVLNVKEGTPS (SEQ ID NO:1017) corresponding to amino acids 128-142 of HUMGRP5E_P5 (SEQ ID NO:157), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMGRP5E_P5 (SEQ ID NO:157), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DSLLQVLNVKEGTPS (SEQ ID NO:1017) in HUMGRP5E_P5 (SEQ ID NO:157).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA—1_P4 (SEQ ID NO:178), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDHLLLLQGEQLRRTT RSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP corresponding to amino acids 1-146 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-146 of AA155578_PEA—1_P4 (SEQ ID NO:178), and a second amino acid sequence being at least 90% homologous to YNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGIL SWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 184-276 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 147-239 of AA155578_PEA—1_P4 (SEQ ID NO:178), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA—1_P4 (SEQ ID NO:178), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PY, having a structure as follows: a sequence starting from any of amino acid numbers 146-x to 146; and ending at any of amino acid numbers 147+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA—1_P6 (SEQ ID NO:179), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1-29 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-29 of AA155578_PEA—1 P6 (SEQ ID NO:179), and a second amino acid sequence being at least 90 % homologous to VKYNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQ GILSWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 182-276 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 30-124 of AA155578_PEA—1_P6 (SEQ ID NO:179), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA—1_P6 (SEQ ID NO: 179), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise WV, having a structure as follows: a sequence starting from any of amino acid numbers 29-x to 29; and ending at any of amino acid numbers 30+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA—1_P8 (SEQ ID NO:180), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1-29 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-29 of AA155578_PEA—1_P8 (SEQ ID NO:180), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GHCGLE (SEQ ID NO:1018) corresponding to amino acids 30-35 of AA155578_PEA—1_P8 (SEQ ID NO:180), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of AA155578-PEA—1_P8 (SEQ ID NO:180), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GHCGLE (SEO ID NO:1018) in AA155578_PEA—1_P8 (SEQ ID NO:180).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA—1_P9 (SEQ ID NO:181), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK corresponding to amino acids 1-90 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-90 of AA155578_PEA—1—P9 (SEQ ID NO:181).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSENA78_P2 (SEQ ID NO:919), comprising a first amino acid sequence being at least 90% homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHP KMISNLQVFAIGPQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN (SEQ ID NO:190), which also corresponds to amino acids 1-81 of HSENA78_P2 (SEQ ID NO:191) According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T94936_PEA—1_P2 (SEQ ID NO:206), comprising a first amino acid sequence being at least 90% homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL corresponding to amino acids 1-150 of Q8TD06 (SEQ ID NO:858), which also corresponds to amino acids 1-150 of T94936_PEA—1_P2 (SEQ ID NO:206).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T94936_PEA—1_P3 (SEQ ID NO:207), comprising a first amino acid sequence being at least 90% homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFV corresponding to amino acids 1-122 of Q8TD06 (SEQ ID NO:858), which also corresponds to amino acids 1-122 of T94936_PEA—1_P3 (SEQ ID NO:207), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMYVISFHQIYKISRNQHSCFYF (SEO ID NO:1019) corresponding to amino acids 123-145 of T94936_PEA—1_P3 (SEQ ID NO:207), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T94936_PEA—1_P3 (SEQ ID NO:207), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMYVISFHQIYKISRNQHSCFYF (SEQ ID NO:1019) in T94936_PEA—1_P3 (SEQ ID NO:207).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 1-95 of SZ14_HUMAN (SEQ ID NO:230), which also corresponds to amino acids 1-95 of Z41644_PEA—1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA—1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA—1-P10 (SEQ ID NO:231).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of Q9NS21 (SEQ ID NO:862), which also corresponds to amino acids 1-95 of Z41644_PEA—1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA—1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA—1P10 (SEQ ID NO:231).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of AAQ89265, which also corresponds to amino acids 1-95 of Z41644_PEA—1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA—1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA—1—P10(SEQ ID NO:231).

According to preferred embodiments of the present invention, there is provided an isolated oligonucleotide, comprising an amplicon selected from the group consisting of SEQ ID NOs: 891 or 894.

According to preferred embodiments of the present invention, there is provided a primer pair, comprising a pair of isolated oligonucleotides capable of amplifying the above. Optionally, the pair of isolated oligonucleotides is selected from the group consisting of: SEQ NOs 889 and 890; or 892 and 893.

According to preferred embodiments of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence as described herein. Optionally, the epitope may comprise a tail, head, or edge portion as described herein.

According to preferred embodiments of the present invention, the antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein.

According to preferred embodiments of the present invention, there is provided an kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant as described herein. Optionally, the kit comprises a NAT-based technology. Preferably, the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence as described herein. Optionally, the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence as described herein.

Optionally, the kit comprises an antibody as described herein. Preferably, the kit further comprises at least one reagent for performing an ELISA or a Western blot.

According to preferred embodiments of the present invention, there is provided a method for detecting breast cancer, comprising detecting overexpression of a splice variant as described herein.

Optionally detecting overexpression is performed with a NAT-based technology. Preferably, detecting overexpression is performed with an immunoassay. More preferably, the immunoassay comprises an antibody as described herein.

According to preferred embodiments of the present invention, there is provided a biomarker capable of detecting breast cancer, comprising any of the above nucleic acid sequences or a fragment thereof, or any of the above amino acid sequences or a fragment thereof.

According to preferred embodiments of the present invention, preferably any of the above nucleic acid and/or amino acid sequences further comprises any sequence having at least about 70%, preferably at least about 80%, more preferably at least about 90%, most preferably at least about 95% homology thereto.

Unless otherwise noted, all experimental data relates to variants of the present invention, named according to the segment being tested (as expression was tested through RT-PCR as described).

All nucleic acid sequences and/or amino acid sequences shown herein as embodiments of the present invention relate to their isolated form, as isolated polynucleotides (including for all transcripts), oligonucleotides (including for all segments, amplicons and primers), peptides (including for all tails, bridges, insertions or heads, optionally including other antibody epitopes as described herein) and/or polypeptides (including for all proteins). It should be noted that oligonucleotide and polynucleotide, or peptide and polypeptide, may optionally be used interchangeably.

Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). All of these are hereby incorporated by reference as if fully set forth herein. As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is schematic summary of cancer biomarkers selection engine and the wet validation stages.

FIG. 2. Schematic illustration, depicting grouping of transcripts of a given cluster based on presence or absence of unique sequence regions.

FIG. 3 is schematic summary of quantitative real-time PCR analysis.

FIG. 4 is schematic presentation of the oligonucleotide based microarray fabrication.

FIG. 5 is schematic summary of the oligonucleotide based microarray experimental flow.

FIG. 6 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T10888, demonstrating overexpression in colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma.

FIG. 7 is a histogram showing expression of the CEA6_HUMAN (SEQ ID NO:13) Carcinoembryonic antigen-related cell adhesion molecule 6 (T10888) transcripts, which are detectable by amplicon as depicted in sequence name T10888 junc11-17, in normal and cancerous breast tissues.

FIG. 8 is a histogram showing the expression of CEA6_HUMAN (SEQ ID NO:13) Carcinoembryonic antigen-related cell adhesion molecule 6 T10888 transcripts which are detectable by amplicon as depicted in sequence name T10888junc11-17 (SEQ ID NO:832) in different normal tissues.

FIG. 9 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T39971, demonstrating overexpression in liver cancer, lung malignant tumors and pancreas carcinoma.

FIG. 10 is a histogram showing the expression of of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971 junc23-33 (SEQ ID NO:836) in normal and cancerous breast tissues.

FIG. 11 is a histogram showing the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), antisense to SARM1 (T23434), T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971junc23-33, in different normal tissues.

FIG. 12 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster Z21368, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

FIG. 13 is a histogram showing the expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39 (SEQ ID NO:844), in normal and cancerous breast tissues.

FIG. 14 is a histogram showing the expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39 (SEQ ID NO:844), in different normal tissues.

FIG. 15 is a histogram showing the expression of SUL 1_HUMAN—Extracellular sulfatase Sulf-1 Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368junc17-21 (SEQ ID NO:847) in normal and cancerous breast tissues.

FIG. 16 is a histogram showing the expression of SUL 1_HUMAN—Extracellular sulfatase Sulf-1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368junc17-21, in different normal tissues.

FIG. 17 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T59832, demonstrating overexpression in brain malignant tumors, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

FIG. 18 is a histogram showing low over expression observed for cluster T59832, amplicon name: T59832 junc6-25-26 (SEQ ID NO:854), in one experiment carried out with breast cancer samples panel.

FIG. 19 is a histogram showing the expression of GRP_HUMAN—gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted insequence name HUMGRP5Ejunc3-7 (SEQ ID NO:857) in normal and cancerous breast tissues.

FIG. 20 is a histogram showing the expression of GRP_HUMAN—gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7 (SEQ ID NO:857), in different normal tissues.

FIG. 21 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster AA155578, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

FIG. 22 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSENA78, demonstrating overexpression in epithelial malignant tumors and lung malignant tumors.

FIG. 23 is a histogram showing the expression of Homo sapiens breast cancer membrane protein 11 (BCMP11) T94936 transcripts which are detectable by amplicon as depicted in sequence name T94936 seg14 (SEQ ID NO:861) in normal and cancerous Breast tissues.

FIG. 24 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster Z41644, demonstrating overexpression in lung malignant tumors, breast malignant tumors and pancreas carcinoma.

FIG. 25 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster M85491, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues.

FIG. 26 is a histogram showing the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 (SEQ ID NO:866) in normal and cancerous breast tissues.

FIG. 27 is a histogram showing the expression of Ephrin type-B receptor 2 precursor M85491 transcripts,-which are detectable by amplicon as depicted in sequence name M85491 seg24, in different normal tissues.

FIG. 28 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSSTROL3, demonstrating overexpression in transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

FIG. 29A is a histogram showing the expression of Expression of Stromelysin-3 precursor (SEQ ID NO:270) (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) SL-3 HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:869) in normal and cancerous breast tissues.

FIG. 29B is a histogram showing the expression of Stromelysin-3 precursor (SEQ ID NO:270) (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:869), in different normal tissues.

FIGS. 30A-30C shows histograms showing over expression of various Stromelysin-3 precursor (SEQ ID NO:270) transcripts in cancerous breast samples relative to the normal samples.

FIG. 31 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster R75793, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues.

FIG. 32 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMCA1XIA, demonstrating overexpression in bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

FIG. 33 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster R20779, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

FIG. 34 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSS100PCB, demonstrating overexpression in a mixture of malignant tumors from different tissues.

FIG. 35 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSCOC4, demonstrating overexpression in brain malignant tumors, a mixture of malignant tumors from different-tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

FIG. 36 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMTREFAC, demonstrating overexpression in a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

FIG. 37 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMOSTRO, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors, breast malignant tumors, ovarian carcinoma and skin malignancies.

FIG. 38 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster R11723, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors.

FIG. 39 is a histogram showing the expression of of R11723 transcripts which are detectable by amplicon as depicted in sequence name R11723 seg13 (SEQ ID NO:891) in normal and cancerous breast tissues.

FIG. 40 is a histogram showing the expression of R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723seg13 (SEQ ID NO:891), in different normal tissues.

FIGS. 41A and B are histograms showing the expression of R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723 junc11-18 (SEQ ID NO:894) in normal and cancerous breast tissues (FIG. 41A) or on a panel of normal tissues (FIG. 41B).

FIG. 42 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T46984, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

FIG. 43 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSMUC 1A, demonstrating overexpression in a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

FIGS. 44-47 are histograms showing the combined expression of 8 sequences (T10888seg11-17, HUMGR5Ejunc3-7, HSSTROL3seg24, T94936 Seg 14, Z21368 seg39, Z21368junc17-21 T59832jun6-25-26 and M85491seg24 (SEQ ID NO:866)) in normal and cancerous breast tissues.

FIG. 48 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSU33147, demonstrating overexpression in a mixture of malignant tumors from different tissues.

DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention is of novel markers for breast cancer that are both sensitive and accurate. Furthermore, at least certain of these markers are able to distinguish between different stages of breast cancer, such as 1. Ductal carcinoma (in-situ, invasive) 2. Lobular carcinoma (is-situ, invasive) 3. inflammatory breast cancer 4. Mucinous carcinoma 5. Tubular carcinoma 6. Paget's disease of nipple, alone or in combination; or one of the indicative conditions described above.

The markers of the present invention, alone or in combination, can be used for prognosis, prediction, screening, early diagnosis, staging, therapy selection and treatment monitoring of breast cancer. For example, optionally and preferably, these markers may be used for staging breast cancer and/or monitoring the progression of the disease. Furthermore, the markers of the present invention, alone or in combination, can be used for detection of the source of metastasis found in anatomical places other then breast. Also, one or more of the markers may optionally be used in combination with one or more other breast cancer markers (other than those described herein).

Biomolecular sequences (amino acid and/or nucleic acid sequences) uncovered using the methodology of the present invention and described herein can be efficiently utilized as tissue or pathological markers and/or as drugs or drug targets for treating or preventing a disease.

These markers are specifically released to the bloodstream under conditions of breast cancer (or one of the above indicative conditions), and/or are otherwise expressed at a much higher level and/or specifically expressed in breast cancer tissue or cells, and/or tissue or cells under one of the above indicative conditions. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer and/or a condition that it is indicative of a higher risk for breast cancer.

The present invention therefore also relates to diagnostic assays for breast cancer and/or an indicative condition, and methods of use of such markers for detection of breast cancer and/or an indicative condition, optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample.

According to a preferred embodiment of the present invention, use of the marker optionally and preferably permits a non-cancerous breast disease state to be distinguished from breast cancer and/or an indicative condition. A non limiting example of a non-cancerous breast disease state includes breast fibrosis and/or cysts. According to another preferred embodiment of the present invention, use of the marker optionally and preferably permits an indicative condition to be distinguished from breast cancer.

In another embodiment, the present invention relates to bridges, tails, heads and/or insertions, and/or analogs, homologs and derivatives of such peptides. Such bridges, tails, heads and/or insertions are described in greater detail below with regard to the Examples.

As used herein a “tail” refers to a peptide sequence at the end of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a tail may optionally be considered as a chimera, in that at least a first portion of the splice variant is typically highly homologous (often 100% identical) to a portion of the corresponding known protein, while at least a second portion of the variant comprises the tail.

As used herein a “head” refers to a peptide sequence at the beginning of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a head may optionally be considered as a chimera, in that at least a first portion of the splice variant comprises the head, while at least a second portion is typically highly homologous (often 100% identical) to a portion of the corresponding known protein.

As used herein “an edge portion” refers to a connection between two portions of a splice variant according to the present invention that were not joined in the wild type or known protein. An edge may optionally arise due to a join between the above “known protein” portion of a variant and the tail, for example, and/or may occur if an internal portion of the wild type sequence is no longer present, such that two portions of the sequence are now contiguous in the splice variant that were not contiguous in the known protein. A “bridge” may optionally be an edge portion as described above, but may also include a join between a head and a “known protein” portion of a variant, or a join between a tail and a “known protein” portion of a variant, or a join between an insertion and a “known protein” portion of a variant.

Optionally and preferably, a bridge between a tail or a head or a unique insertion, and a “known protein” portion of a variant, comprises at least about 10 amino acids, more preferably at least about 20 amino acids, most preferably at least about 30 amino acids, and even more preferably at least about 40 amino acids, in which at least one amino acid is from the tail/head/insertion and at least one amino acid is from the “known protein” portion of a variant. Also optionally, the bridge may comprise any number of amino acids from about 10 to about 40 amino acids (for example, 10, 11, 12, 13 . . . 37, 38, 39, 40 amino acids in length, or any number in between).

It should be noted that a bridge cannot be extended beyond the length of the sequence in either direction, and it should be assumed that every bridge description is to be read in such manner that the bridge length does not extend beyond the sequence itself.

Furthermore, bridges are described with regard to a sliding window in certain contexts below. For example, certain descriptions of the bridges feature the following format: a bridge between two edges (in which a portion of the known protein is not present in the variant) may optionally be described as follows: a bridge portion of CONTIG-NAME_P1 (representing the name of the protein), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise XX (2 amino acids in the center of the bridge, one from each end of the edge), having a structure as follows (numbering according to the sequence of CONTIG-NAME_P1): a sequence starting from any of amino acid numbers 49-x to 49 (for example); and ending at any of amino acid numbers 50+((n−2)−x) (for example), in which x varies from 0 to n−2. In this example, it should also be read as including bridges in which n is any number of amino acids between 10-50 amino acids in length. Furthermore, the bridge polypeptide cannot extend beyond the sequence, so it should be read such that 49-x (for example) is not less than 1, nor 50+((n−2)−x) (for example) greater than the total sequence length.

In another embodiment, this invention provides antibodies specifically recognizing the splice variants and polypeptide fragments thereof of this invention. Preferably such antibodies differentially recognize splice variants of the present invention but do not recognize a corresponding known protein (such known proteins are discussed with regard to their splice variants in the Examples below).

In another embodiment, this invention provides an isolated nucleic acid molecule encoding for a splice variant according to the present invention, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an isolated nucleic acid molecule, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an oligonucleotide of at least about 12 nucleotides, specifically hybridizable with the nucleic acid molecules of this invention. In another embodiment, this invention provides vectors, cells, liposomes and compositions comprising the isolated nucleic acids of this invention.

In another embodiment, this invention provides a method for detecting a splice variant according to the present invention in a biological sample, comprising: contacting a biological sample with an antibody specifically recognizing a splice variant according to the present invention under conditions whereby the antibody specifically interacts with the splice variant in the biological sample but do not recognize known corresponding proteins (wherein the known protein is discussed with regard to its splice variant(s) in the Examples below), and detecting said interaction; wherein the presence of an interaction correlates with the presence of a splice variant in the biological sample.

In another embodiment, this invention provides a method for detecting a splice variant nucleic acid sequences in a biological sample, comprising: hybridizing the isolated nucleic acid molecules or oligonucleotide fragments of at least about a minimum length to a nucleic acid material of a biological sample and detecting a hybridization complex; wherein the presence of a hybridization complex correlates with the presence of a splice variant nucleic acid sequence in the biological sample.

According to the present invention, the splice variants described herein are non-limiting examples of markers for diagnosing breast cancer and/or an indicative condition. Each splice variant marker of the present invention can be used alone or in combination, for various uses, including but not limited to, prognosis, prediction, screening, early diagnosis, determination of progression, therapy selection and treatment monitoring of breast cancer and/or an indicative condition, including a transition from an indicative condition to breast cancer.

According to optional but preferred embodiments of the present invention, any marker according to the present invention may optionally be used alone or combination. Such a combination may optionally comprise a plurality of markers described herein, optionally including any subcombination of markers, and/or a combination featuring at least one other marker, for example a known marker. Furthermore, such a combination may optionally and preferably be used as described above with regard to determining a ratio between a quantitative or semi-quantitative measurement of any marker described herein to any other marker described herein, and/or any other known marker, and/or any other marker. With regard to such a ratio between any marker described herein (or a combination thereof) and a known marker, more preferably the known marker comprises the “known protein” as described in greater detail below with regard to each cluster or gene.

According to other preferred embodiments of the present invention, a splice variant protein or a fragment thereof, or a splice variant nucleic acid sequence or a fragment thereof, may be featured as a biomarker for detecting breast cancer and/or an indicative condition, such that a biomarker may optionally comprise any of the above.

According to still other preferred embodiments, the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence corresponding to a splice variant protein as described herein. Any oligopeptide or peptide relating to such an amino acid sequence or fragment thereof may optionally also (additionally or alternatively) be used as a biomarker, including but not limited to the unique amino acid sequences of these proteins that are depicted as tails, heads, insertions, edges or bridges. The present invention also optionally encompasses antibodies capable of recognizing, and/or being elicited by, such oligopeptides or peptides.

The present invention also optionally and preferably encompasses any nucleic acid sequence or fragment thereof, or amino acid sequence or fragment thereof, corresponding to a splice variant of the present invention as described above, optionally for any application.

Non-limiting examples of methods or assays are described below.

The present invention also relates to kits based upon such diagnostic methods or assays.

Nucleic Acid Sequences and Oligonucleotides

Various embodiments of the present invention encompass nucleic acid sequences described hereinabove; fragments thereof, sequences hybridizable therewith, sequences homologous thereto, sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or artificially induced, either randomly or in a targeted fashion.

The present invention encompasses nucleic acid sequences described herein; fragments thereof, sequences hybridizable therewith, sequences homologous thereto [e.g., at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, least 95% or more say 100% identical to the nucleic acid sequences set forth below], sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or man induced, either randomly or in a targeted fashion. The present invention also encompasses homologous nucleic acid sequences (i.e., which form a part of a polynucleotide sequence of the present invention) which include sequence regions unique to the polynucleotides of the present invention.

In cases where the polynucleotide sequences of the present invention encode previously unidentified polypeptides, the present invention also encompasses novel polypeptides or portions thereof, which are encoded by the isolated polynucleotide and respective nucleic acid fragments thereof described hereinabove.

A “nucleic acid fragment” or an “oligonucleotide” or a “polynucleotide” are used herein interchangeably to refer to a polymer of nucleic acids. A polynucleotide sequence of the present invention refers to a single or double stranded nucleic acid sequences which is isolated and provided in the form of an RNA sequence, a complementary polynucleotide sequence (cDNA), a genomic polynucleotide sequence and/or a composite polynucleotide sequences (e.g., a combination of the above).

As used herein the phrase “complementary polynucleotide sequence” refers to a sequence, which results from reverse transcription of messenger RNA using a reverse transcriptase or any other RNA dependent DNA polymerase. Such a sequence can be subsequently amplified in vivo or in vitro using a DNA dependent DNA polymerase.

As used herein the phrase “genomic polynucleotide sequence” refers to a sequence derived (isolated) from a chromosome and thus it represents a contiguous portion of a chromosome.

As used herein the phrase “composite polynucleotide sequence” refers to a sequence, which is composed of genomic and cDNA sequences. A composite sequence can include some exonal sequences required to encode the polypeptide of the present invention, as well as some intronic sequences interposing therebetween. The intronic sequences can be of any source, including of other genes, and typically will include conserved splicing signal sequences. Such intronic sequences may further include cis acting expression regulatory elements.

Preferred embodiments of the present invention encompass oligonucleotide probes.

An example of an oligonucleotide probe which can be utilized by the present invention is a single stranded polynucleotide which includes a sequence complementary to the unique sequence region of any variant according to the present invention, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein).

Alternatively, an oligonucleotide probe of the present invention can be designed to hybridize with a nucleic acid sequence encompassed by any of the above nucleic acid sequences, particularly the portions specified above, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein).

Oligonucleotides designed according to the teachings of the present invention can be generated according to any oligonucleotide synthesis method known in the art such as enzymatic synthesis or solid phase synthesis. Equipment and reagents for executing solid-phase synthesis are commercially available from, for example, Applied Biosystems. Any other means for such synthesis may also be employed; the actual synthesis of the oligonucleotides is well within the capabilities of one skilled in the art and can be accomplished via established methodologies as detailed in, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes 1-111 Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988) and “Oligonucleotide Synthesis” Gait, M. J., ed. (1984) utilizing solid phase chemistry, e.g. cyanoethyl phosphoramidite followed by deprotection, desalting and purification by for example, an automated trityl-on method or HPLC.

Oligonucleotides used according to this aspect of the present invention are those having a length selected from a range of about 10 to about 200 bases preferably about 15 to about 150 bases, more preferably about 20 to about 100 bases, most preferably about 20 to about 50 bases. Preferably, the oligonucleotide of the present invention features at least 17, at least 18, at least 19, at least 20, at least 22, at least 25, at least 30 or at least 40, bases specifically hybridizable with the biomarkers of the present invention.

The oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3â€Č to 5â€Č phosphodiester linkage.

Preferably used oligonucleotides are those modified at one or more of the backbone, internucleoside linkages or bases, as is broadly described hereinunder.

Specific examples of preferred oligonucleotides useful according to this aspect of the present invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. Oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone, as disclosed in U.S. Pat. Nos: 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466, 677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050.

Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, methyl and other alkyl phosphonates including 3â€Č-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3â€Č-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3â€Č-5â€Č linkages, 2â€Č-5â€Č linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3â€Č-5â€Č to 5â€Č-3â€Č or 2â€Č-5â€Č to 5â€Č-2â€Č. Various salts, mixed salts and free acid for also be used.

Alternatively, modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts, as disclosed in U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439.

Other oligonucleotides which can be used according to the present invention, are those modified in both sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for complementation with the appropriate polynucleotide target. An example for such an oligonucleotide mimetic, includes peptide nucleic acid (PNA). U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Other backbone modifications, which can be used in the present invention are disclosed in U.S. Pat. No: 6,303,374.

Oligonucleotides of the present invention may also include base modifications or substitutions. As used herein, “unmodified” or “natural” bases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified bases include but are not limited to other synthetic and natural bases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further bases particularly useful for increasing the binding affinity of the oligomeric compounds of the invention include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. and are presently preferred base substitutions, even more particularly when combined with 2â€Č-O-methoxyethyl sugar modifications.

Another modification of the oligonucleotides of the invention involves chemically linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., hexyl-S-tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues, a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety, as disclosed in U.S. Pat. No: 6,303,374.

It is not necessary for all positions in a given oligonucleotide molecule to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide.

It will be appreciated that oligonucleotides of the present invention may include further modifications for more efficient use as diagnostic agents and/or to increase bioavailability, therapeutic efficacy and reduce cytotoxicity.

To enable cellular expression of the polynucleotides of the present invention, a nucleic acid construct according to the present invention may be used, which includes at least a coding region of one of the above nucleic acid sequences, and further includes at least one cis acting regulatory element. As used herein, the phrase “cis acting regulatory element” refers to a polynucleotide sequence, preferably a promoter, which binds a trans acting regulator and regulates the transcription of a coding sequence located downstream thereto.

Any suitable promoter sequence can be used by the nucleic acid construct of the present invention.

Preferably, the promoter utilized by the nucleic acid construct of the present invention is active in the specific cell population transformed. Examples of cell type-specific and/or tissue-specific promoters include promoters such as albumin that is liver specific, lymphoid specific promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular promoters of T-cell receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins; [Banerji et al. (1983) Cell 33729-740], neuron-specific promoters such as the neurofilament promoter [Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477], pancreas-specific promoters [Edlunch et al. (1985) Science 230:912-916] or mammary gland-specific promoters such as the milk whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). The nucleic acid construct of the present invention can further include an enhancer, which can be adjacent or distant to the promoter sequence and can function in up regulating the transcription therefrom.

The nucleic acid construct of the present invention preferably further includes an appropriate selectable marker and/or an origin of replication. Preferably, the nucleic acid construct utilized is a shuttle vector, which can propagate both in E. coli (wherein the construct comprises an appropriate selectable marker and origin of replication) and be compatible for propagation in cells, or integration in a gene and a tissue of choice. The construct according to the present invention can be, for example, a plasmid, a bacmid, a phagemid, a cosmid, a phage, a virus or an artificial chromosome.

Examples of suitable constructs include, but are not limited to, pcDNA3, pcDNA3.1 (±), pGL3, PzeoSV2 (±), pDisplay, pEF/myc/cyto, pCMV/myc/cyto each of which is commercially available from Invitrogen Co. (www.invitrogen.com). Examples of retroviral vector and packaging systems are those sold by Clontech, San Diego, Calif., including Retro-X vectors pLNCX and pLXSN, which permit cloning into multiple cloning sites and the trasgene is transcribed from CMV promoter. Vectors derived from Mo-MuLV are also included such as pBabe, where the transgene will be transcribed from the 5â€ČLTR promoter.

Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs, such as adenovirus, lentivirus, Herpes simplex I virus, or adeno-associated virus (AAV) and lipid-based systems. Useful lipids for lipid-mediated transfer of the gene are, for example, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy are viruses, most preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct such as a retroviral construct includes at least one transcriptional promoter/enhancer or locus-defining element(s), or other elements that control gene expression by other means such as alternate splicing, nuclear RNA export, or post-translational modification of messenger. Such vector constructs also include a packaging signal, long terminal repeats (LTRs) or portions thereof, and positive and negative strand primer binding sites appropriate to the virus used, unless it is already present in the viral construct. In addition, such a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed. Preferably the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the polypeptide variants of the present invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. By way of example, such constructs will typically include a 5â€Č LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3â€Č LTR or a portion thereof. Other vectors can be used that are non-viral, such as cationic lipids, polylysine, and dendrimers.

Hybridization Assays

Detection of a nucleic acid of interest in a biological sample may optionally be effected by hybridization-based assays using an oligonucleotide probe (non-limiting examples of probes according to the present invention were previously described).

Traditional hybridization assays include PCR, RT-PCR, Real-time PCR, RNase protection, in-situ hybridization, primer extension, Southern blots (DNA detection), dot or slot blots (DNA, RNA), and Northern blots (RNA detection) (NAT type assays are described in greater detail below). More recently, PNAs have been described (Nielsen et al. 1999, Current Opin. Biotechnol. 10:71-75). Other detection methods include kits containing probes on a dipstick setup and the like.

Hybridization based assays which allow the detection of a variant of interest (i.e., DNA or RNA) in a biological sample rely on the use of oligonucleotides which can be 10, 15, 20, or 30 to 100 nucleotides long preferably from 10 to 50, more preferably from 40 to 50 nucleotides long.

Thus, the isolated polynucleotides (oligonucleotides) of the present invention are preferably hybridizable with any of the herein described nucleic acid sequences under moderate to stringent hybridization conditions.

Moderate to stringent hybridization conditions are characterized by a hybridization solution such as containing 10% dextrane sulfate, 1 M NaCl, 1% SDS and 5×106 cpm 32P labeled probe, at 65° C., with a final wash solution of 0.2×SSC and 0.1% SDS and final wash at 65° C and whereas moderate hybridization is effected using a hybridization solution containing 10% dextrane sulfate, 1 M NaCl, 1% SDS and 5×106 cpm 32p labeled probe, at 65° C, with a final wash solution of 1×SSC and 0.1% SDS and final wash at 50° C.

More generally, hybridization of short nucleic acids (below 200 bp in length, e.g. 17-40 bp in length) can be effected using the following exemplary hybridization protocols which can be modified according to the desired stringency; (i) hybridization solution of 6×SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 ÎŒg/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature of 1-1.5° C. below the Tm, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5° C. below the Tm; (ii) hybridization solution of 6×SSC and 0.1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 ÎŒg/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature of 2-2.5° C. below the Tm, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5° C. below the Tm, final wash solution of 6×SSC, and final wash at 22° C.; (iii) hybridization solution of 6×SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 ÎŒg/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature.

The detection of hybrid duplexes can be carried out by a number of methods. Typically, hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected. Such labels refer to radioactive, fluorescent, biological or enzymatic tags or labels of standard use in the art. A label can be conjugated to either the oligonucleotide probes or the nucleic acids derived from the biological sample.

Probes can be labeled according to numerous well known methods. Non-limiting examples of radioactive labels include 3H, 14C, 32P, and 35S. Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies. Other detectable markers for use with probes, which can enable an increase in sensitivity of the method of the invention, include biotin and radio-nucleotides. It will become evident to the person of ordinary skill that the choice of a particular label dictates the manner in which it is bound to the probe.

For example, oligonucleotides of the present invention can be labeled subsequent to synthesis, by incorporating biotinylated dNTPs or rNTP, or some similar means (e.g., photo-cross-linking a psoralen derivative of biotin to RNAs), followed by addition of labeled streptavidin (e.g., phycoerythrin-conjugated streptavidin) or the equivalent. Alternatively, when fluorescently-labeled oligonucleotide probes are used, fluorescein, lissamine, phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, FluorX (Amersham) and others [e.g., Kricka et al. (1992), Academic Press San Diego, Calif.] can be attached to the oligonucleotides.

Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes.

It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. For instance, samples may be hybridized to an irrelevant probe and treated with RNAse A prior to hybridization, to assess false hybridization.

Although the present invention is not specifically dependent on the use of a label for the detection of a particular nucleic acid sequence, such a label might be beneficial, by increasing the sensitivity of the detection. Furthermore, it enables automation. Probes can be labeled according to numerous well known methods.

As commonly known, radioactive nucleotides can be incorporated into probes of the invention by several methods. Non-limiting examples of radioactive labels include 3H, 14C, 32P, and 35S.

Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes.

It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays.

Probes of the invention can be utilized with naturally occurring sugar-phosphate backbones as well as modified backbones including phosphorothioates, dithionates, alkyl phosphonates and a-nucleotides and the like. Probes of the invention can be constructed of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA.

NAT Assays

Detection of a nucleic acid of interest in a biological sample may also optionally be effected by NAT-based assays, which involve nucleic acid amplification technology, such as PCR for example (or variations thereof such as real-time PCR for example).

As used herein, a “primer” defines an oligonucleotide which is capable of annealing to (hybridizing with) a target sequence, thereby creating a double stranded region which can serve as an initiation point for DNA synthesis under suitable conditions.

Amplification of a selected, or target, nucleic acid sequence may be carried out by a number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous amplification techniques have been described and can be readily adapted to suit particular needs of a person of ordinary skill. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-based amplification, the q3 replicase system and NASBA (Kwoh et al., 1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260; and Sambrook et al., 1989, supra).

The terminology “amplification pair” (or “primer pair”) refers herein to a pair of oligonucleotides (oligos) of the present invention, which are selected to be used together in amplifying a selected nucleic acid sequence by one of a number of types of amplification processes, preferably a polymerase chain reaction. Other types of amplification processes include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based amplification, as explained in greater detail below. As commonly known in the art, the oligos are designed to bind to a complementary sequence under selected conditions.

In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions which favor the amplification of the most abundant differentially expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA. In another preferred embodiment, the amplification of the differentially expressed nucleic acids is carried out simultaneously. It will be realized by a person skilled in the art that such methods could be adapted for the detection of differentially expressed proteins instead of differentially expressed nucleic acid sequences.

The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be obtained according to well known methods.

Oligonucleotide primers of the present invention may be of any suitable length, depending on the particular assay format and the particular needs and targeted genomes employed. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, and they may be adapted to be especially suited to a chosen nucleic acid amplification system. As commonly known in the art, the oligonucleotide primers can be designed by taking into consideration the melting point of hybridization thereof with its targeted sequence (Sambrook et al., 1989, Molecular Cloning—A Laboratory Manual, 2nd Edition, CSH Laboratories; Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N.Y.).

It will be appreciated that antisense oligonucleotides may be employed to quantify expression of a splice isoform of interest. Such detection is effected at the pre-mRNA level. Essentially the ability to quantitate transcription from a splice site of interest can be effected based on splice site accessibility. Oligonucleotides may compete with splicing factors for the splice site sequences. Thus, low activity of the antisense oligonucleotide is indicative of splicing activity.

The polymerase chain reaction and other nucleic acid amplification reactions are well known in the art (various non-limiting examples of these reactions are described in greater detail below). The pair of oligonucleotides according to this aspect of the present invention are preferably selected to have compatible melting temperatures (Tm), e.g., melting temperatures which differ by less than that 7° C., preferably less than 5° C., more preferably less than 4° C., most preferably less than 3° C., ideally between 3° C. and 0° C.

Polymerase Chain Reaction (PCR): The polymerase chain reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a method of increasing the concentration of a segment of target sequence in a mixture of genomic DNA without cloning or purification. This technology provides one approach to the problems of low target sequence concentration. PCR can be used to directly increase the concentration of the target to an easily detectable level. This process for amplifying the target sequence involves the introduction of a molar excess of two oligonucleotide primers which are complementary to their respective strands of the double-stranded target sequence to the DNA mixture containing the desired target sequence. The mixture is denatured and then allowed to hybridize. Following hybridization, the primers are extended with polymerase so as to form complementary strands. The steps of denaturation, hybridization (annealing), and polymerase extension (elongation) can be repeated as often as needed, in order to obtain relatively high concentrations of a segment of the desired target sequence.

The length of the segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and, therefore, this length is a controllable parameter. Because the desired segments of the target sequence become the dominant sequences (in terms of concentration) in the mixture, they are said to be “PCR-amplified.”

Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes referred to as “Ligase Amplification Reaction” (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids. In LCR, four oligonucleotides, two adjacent oligonucleotides which uniquely hybridize to one strand of target DNA, and a complementary set of adjacent oligonucleotides, which hybridize to the opposite strand are mixed and DNA ligase is added to the mixture. Provided that there is complete complementarity at the junction, ligase will covalently link each set of hybridized molecules. Importantly, in LCR, two probes are ligated together only when they base-pair with sequences in the target sample, without gaps or mismatches. Repeated cycles of denaturation, and ligation amplify a short segment of DNA. LCR has also been used in combination with PCR to achieve enhanced detection of single-base changes: see for example Segev, PCT Publication No. W09001069 A1 (1990). However, because the four oligonucleotides used in this assay can pair to form two short ligatable fragments, there is the potential for the generation of target-independent background signal. The use of LCR for mutant screening is limited to the examination of specific nucleic acid positions.

Self-Sustained Synthetic Reaction (3SR/NASBA): The self-sustained sequence replication reaction (3SR) is a transcription-based in vitro amplification system that can exponentially amplify RNA sequences at a uniform temperature. The amplified RNA can then be utilized for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5â€Č end of the sequence of interest. In a cocktail of enzymes and substrates that includes a second primer, reverse transcriptase, RNase H, RNA polymerase and ribo-and deoxyribonucleoside triphosphates, the target sequence undergoes repeated rounds of transcription, cDNA synthesis and second-strand synthesis to amplify the area of interest. The use of 3SR to detect mutations is kinetically limited to screening small segments of DNA (e.g., 200-300 base pairs).

Q-Beta (QÎČ) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for QÎČ replicase. A previously identified major problem with false positives resulting from the replication of unhybridized probes has been addressed through use of a sequence-specific ligation step. However, available thermostable DNA ligases are not effective on this RNA substrate, so the ligation must be performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents the use of high temperature as a means of achieving specificity as in the LCR, the ligation event can be used to detect a mutation at the junction site, but not elsewhere.

A successful diagnostic method must be very specific. A straight-forward method of controlling the specificity of nucleic acid hybridization is by controlling the temperature of the reaction. While the 3SR/NASBA, and QÎČ systems are all able to generate a large quantity of signal, one or more of the enzymes involved in each cannot be used at high temperature (i.e., >55 degrees C). Therefore the reaction temperatures cannot be raised to prevent non-specific hybridization of the probes. If probes are shortened in order to make them melt more easily at low temperatures, the likelihood of having more than one perfect match in a complex genome increases. For these reasons, PCR and LCR currently dominate the research field in detection technologies.

The basis of the amplification procedure in the PCR and LCR is the fact that the products of one cycle become usable templates in all subsequent cycles, consequently doubling the population with each cycle. The final yield of any such doubling system can be expressed as: (1+X)n=y, where “X” is the mean efficiency (percent copied in each cycle), “n” is the number of cycles, and “y” is the overall efficiency, or yield of the reaction. If every copy of a target DNA is utilized as a template in every cycle of a polymerase chain reaction, then the mean efficiency is 100%. If 20 cycles of PCR are performed, then the yield will be 220, or 1,048,576 copies of the starting material. If the reaction conditions reduce the mean efficiency to 85%, then the yield in those 20 cycles will be only 1.8520, or 220,513 copies of the starting material. In other words, a PCR running at 85% efficiency will yield only 21% as much final product, compared to a reaction running at 100% efficiency. A reaction that is reduced to 50% mean efficiency will yield less than 1% of the possible product.

In practice, routine polymerase chain reactions rarely achieve the theoretical maximum yield, and PCRs are usually run for more than 20 cycles to compensate for the lower yield. At 50% mean efficiency, it would take 34 cycles to achieve the million-fold amplification theoretically possible in 20, and at lower efficiencies, the number of cycles required becomes prohibitive. In addition, any background products that amplify with a better mean efficiency than the intended target will become the dominant products.

Also, many variables can influence the mean efficiency of PCR, including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, and buffer composition, to name but a few. Contamination of the reaction with exogenous DNA (e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major consideration. Reaction conditions must be carefully optimized for each different primer pair and target sequence, and the process can take days, even for an experienced investigator. The laboriousness of this process, including numerous technical considerations and other factors, presents a significant drawback to using PCR in the clinical setting. Indeed, PCR has yet to penetrate the clinical market in a significant way. The same concerns arise with LCR, as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. In addition, both methods require expensive equipment, capable of precise temperature cycling.

Many applications of nucleic acid detection technologies, such as in studies of allelic variation, involve not only detection of a specific sequence in a complex background, but also the discrimination between sequences with few, or single, nucleotide differences. One method of the detection of allele-specific variants by PCR is based upon the fact that it is difficult for Taq polymerase to synthesize a DNA strand when there is a mismatch between the template strand and the 3â€Č end of the primer. An allele-specific variant may be detected by the use of a primer that is perfectly matched with only one of the possible alleles; the mismatch to the other allele acts to prevent the extension of the primer, thereby preventing the amplification of that sequence. This method has a substantial limitation in that the base composition of the mismatch influences the ability to prevent extension across the mismatch, and certain mismatches do not prevent extension or have only a minimal effect.

A similar 3â€Č-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the thermostable ligase, but LCR still has the drawback of target-independent background ligation products initiating the amplification. Moreover, the combination of PCR with subsequent LCR to identify the nucleotides at individual positions is also a clearly cumbersome proposition for the clinical laboratory.

The direct detection method according to various preferred embodiments of the present invention may be, for example a cycling probe reaction (CPR) or a branched DNA analysis.

When a sufficient amount of a nucleic acid to be detected is available, there are advantages to detecting that sequence directly, instead of making more copies of that target, (e.g., as in PCR and LCR). Most notably, a method that does not amplify the signal exponentially is more amenable to quantitative analysis. Even if the signal is enhanced by attaching multiple dyes to a single oligonucleotide, the correlation between the final signal intensity and amount of target is direct. Such a system has an additional advantage that the products of the reaction will not themselves promote further reaction, so contamination of lab surfaces by the products is not as much of a concern. Recently devised techniques have sought to eliminate the use of radioactivity and/or improve the sensitivity in automatable formats. Two examples are the “Cycling Probe Reaction” (CPR), and “Branched DNA” (bDNA).

Cycling probe reaction (CPR): The cycling probe reaction (CPR), uses a long chimeric oligonucleotide in which a central portion is made of RNA while the two termini are made of DNA. Hybridization of the probe to a target DNA and exposure to a thermostable RNase H causes the RNA portion to be digested. This destabilizes the remaining DNA portions of the duplex, releasing the remainder of the probe from the target DNA and allowing another probe molecule to repeat the process. The signal, in the form of cleaved probe molecules, accumulates at a linear rate. While the repeating process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNases that may carried through sample preparation.

Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched structures that allow each individual oligonucleotide to carry 35 to 40 labels (e.g., alkaline phosphatase enzymes). While this enhances the signal from a hybridization event, signal from non-specific binding is similarly increased.

The detection of at least one sequence change according to various preferred embodiments of the present invention may be accomplished by, for example restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF).

The demand for tests which allow the detection of specific nucleic acid sequences and sequence changes is growing rapidly in clinical diagnostics. As nucleic acid sequence data for genes from humans and pathogenic organisms accumulates, the demand for fast, cost-effective, and easy-to-use tests for as yet mutations within specific sequences is rapidly increasing.

A handful of methods have been devised to scan nucleic acid segments for mutations. One option is to determine the entire gene sequence of each test sample (e.g., a bacterial isolate). For sequences under approximately 600 nucleotides, this may be accomplished using amplified material (e.g., PCR reaction products). This avoids the time and expense associated with cloning the segment of interest. However, specialized equipment and highly trained personnel are required, and the method is too labor-intense and expensive to be practical and effective in the clinical setting.

In view of the difficulties associated with sequencing, a given segment of nucleic acid may be characterized on several other levels. At the lowest resolution, the size of the molecule can be determined by electrophoresis by comparison to a known standard run on the same gel. A more detailed picture of the molecule may be achieved by cleavage with combinations of restriction enzymes prior to electrophoresis, to allow construction of an ordered map. The presence of specific sequences within the fragment can be detected by hybridization of a labeled probe, or the precise nucleotide sequence can be determined by partial chemical degradation or by primer extension in the presence of chain-terminating nucleotide analogs.

Restriction fragment length polymorphism (RFLP): For detection of single-base differences between like sequences, the requirements of the analysis are often at the highest level of resolution. For cases in which the position of the nucleotide in question is known in advance, several methods have been developed for examining single base changes without direct sequencing. For example, if a mutation of interest happens to fall within a restriction recognition sequence, a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis).

Single point mutations have been also detected by the creation or destruction of RFLPs. Mutations are detected and localized by the presence and size of the RNA fragments generated by cleavage at the mismatches. Single nucleotide mismatches in DNA heteroduplexes are also recognized and cleaved by some chemicals, providing an alternative strategy to detect single base substitutions, generically named the “Mismatch Chemical Cleavage” (MCC). However, this method requires the use of osmium tetroxide and piperidine, two highly noxious chemicals which are not suited for use in a clinical laboratory.

RFLP analysis suffers from low sensitivity and requires a large amount of sample. When RFLP analysis is used for the detection of point mutations, it is, by its nature, limited to the detection of only those single base changes which fall within a restriction sequence of a known restriction endonuclease. Moreover, the majority of the available enzymes have 4 to 6 base-pair recognition sequences, and cleave too frequently for many large-scale DNA manipulations. Thus, it is applicable only in a small fraction of cases, as most mutations do not fall within such sites.

A handful of rare-cutting restriction enzymes with 8 base-pair specificities have been isolated and these are widely used in genetic mapping, but these enzymes are few in number, are limited to the recognition of G+C-rich sequences, and cleave at sites that tend to be highly clustered. Recently, endonucleases encoded by group I introns have been discovered that might have greater than 12 base-pair specificity, but again, these are few in number.

Allele specific oligonucleotide (ASO): If the change is not in a recognition sequence, then allele-specific oligonucleotides (ASOs), can be designed to hybridize in proximity to the mutated nucleotide, such that a primer extension or ligation event can bused as the indicator of a match or a mis-match. Hybridization with radioactively labeled allelic specific oligonucleotides (ASO) also has been applied to the detection of specific point mutations. The method is based on the differences in the melting temperature of short DNA fragments differing by a single nucleotide. Stringent hybridization and washing conditions can differentiate between mutant and wild-type alleles. The ASO approach applied to PCR products also has been extensively utilized by various researchers to detect and characterize point mutations in ras genes and gsp/gip oncogenes. Because of the presence of various nucleotide changes in multiple positions, the ASO method requires the use of many oligonucleotides to cover all possible oncogenic mutations.

With either of the techniques described above (i.e., RFLP and ASO), the precise location of the suspected mutation must be known in advance of the test. That is to say, they are inapplicable when one needs to detect the presence of a mutation within a gene or sequence of interest.

Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE): Two other methods rely on detecting changes in electrophoretic mobility in response to minor sequence changes. One of these methods, termed “Denaturing Gradient Gel Electrophoresis” (DGGE) is based on the observation that slightly different sequences will display different patterns of local melting when electrophoretically resolved on a gradient gel. In this manner, variants can be distinguished, as differences in melting properties of homoduplexes versus heteroduplexes differing in a single nucleotide can detect the presence of mutations in the target sequences because of the corresponding changes in their electrophoretic mobilities. The fragments to be analyzed, usually PCR products, are “clamped” at one end by a long stretch of G-C base pairs (30-80) to allow complete denaturation of the sequence of interest without complete dissociation of the strands. The attachment of a GC “clamp” to the DNA fragments increases the fraction of mutations that can be recognized by DGGE. Attaching a GC clamp to one primer is critical to ensure that the amplified sequence has a low dissociation temperature. Modifications of the technique have been developed, using temperature gradients, and the method can be also applied to RNA:RNA duplexes.

Limitations on the utility of DGGE include the requirement that the denaturing conditions must be optimized for each type of DNA to be tested. Furthermore, the method requires specialized equipment to prepare the gels and maintain the needed high temperatures during electrophoresis. The expense associated with the synthesis of the clamping tail on one oligonucleotide for each sequence to be tested is also a major consideration. In addition, long running times are required for DGGE. The long running time of DGGE was shortened in a modification of DGGE called constant denaturant gel electrophoresis (CDGE). CDGE requires that gels be performed under different denaturant conditions in order to reach high efficiency for the detection of mutations.

A technique analogous to DGGE, termed temperature gradient gel electrophoresis (TGGE), uses a thermal gradient rather than a chemical denaturant gradient. TGGE requires the use of specialized equipment which can generate a temperature gradient perpendicularly oriented relative to the electrical field. TGGE can detect mutations in relatively small fragments of DNA therefore scanning of large gene segments requires the use of multiple PCR products prior to running the gel.

Single-Strand Conformation Polymorphism (SSCP): Another common method, called “Single-Strand Conformation Polymorphism” (SSCP) was developed by Hayashi, Sekya and colleagues and is based on the observation that single strands of nucleic acid can take on characteristic conformations in non-denaturing conditions, and these conformations influence electrophoretic mobility. The complementary strands assume sufficiently different structures that one strand may be resolved from the other. Changes in sequences within the fragment will also change the conformation, consequently altering the mobility and allowing this to be used as an assay for sequence variations.

The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that is labeled on both strands, followed by slow electrophoretic separation on a non-denaturing polyacrylamide gel, so that intra-molecular interactions can form and not be disturbed during the run. This technique is extremely sensitive to variations in gel composition and temperature. A serious limitation of this method is the relative difficulty encountered in comparing data generated in different laboratories, under apparently similar conditions.

Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technique combines components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing reaction is performed using one dideoxy terminator and then the reaction products are electrophoresed on nondenaturing polyacrylamide gels to detect alterations in mobility of the termination segments as in SSCP analysis. While ddF is an improvement over SSCP in terms of increased sensitivity, ddF requires the use of expensive dideoxynucleotides and this technique is still limited to the analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-300 bases for optimal detection of mutations).

In addition to the above limitations, all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed. For the direct sequencing approach, sequences of greater than 600 base pairs require cloning, with the consequent delays and expense of either deletion sub-cloning or primer walking, in order to cover the entire fragment. SSCP and DGGE have even more severe size limitations. Because of reduced sensitivity to sequence changes, these methods are not considered suitable for larger fragments. Although SSCP is reportedly able to detect 90% of single-base substitutions within a 200 base-pair fragment, the detection drops to less than 50% for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases as the length of the fragment reaches 500 base-pairs. The ddF technique, as a combination of direct sequencing and SSCP, is also limited by the relatively small size of the DNA that can be screened.

According to a presently preferred embodiment of the present invention the step of searching for any of the nucleic acid sequences described here, in tumor cells or in cells derived from a cancer patient is effected by any suitable technique, including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, QÎČ-Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis and dideoxy fingerprinting.

Detection may also optionally be performed with a chip or other such device. The nucleic acid sample which includes the candidate region to be analyzed is preferably isolated, amplified and labeled with a reporter group. This reporter group can be a fluorescent group such as phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station. describe the fabrication of fluidics devices and particularly microcapillary devices, in silicon and glass substrates.

Once the reaction is completed, the chip is inserted into a scanner and patterns of hybridization are detected. The hybridization data is collected, as a signal emitted from the reporter groups already incorporated into the nucleic acid, which is now bound to the probes attached to the chip. Since the sequence and position of each probe immobilized on the chip is known, the identity of the nucleic acid hybridized to a given probe can be determined.

It will be appreciated that when utilized along with automated equipment, the above described detection methods can be used to screen multiple samples for a disease and/or pathological condition both rapidly and easily.

Amino Acid Sequences and Peptides

The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. Polypeptides can be modified, e.g., by the addition of carbohydrate residues to form glycoproteins. The terms “polypeptide,” “peptide” and “protein” include glycoproteins, as well as non-glycoproteins.

Polypeptide products can be biochemically synthesized such as by employing standard solid phase techniques. Such methods include but are not limited to exclusive solid phase synthesis, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry.

Solid phase polypeptide synthesis procedures are well known in the art and further described by John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984).

Synthetic polypeptides can optionally be purified by preparative high performance liquid chromatography [Creighton T. (1983) Proteins, structures and molecular principles. WH Freeman and Co. N.Y.], after which their composition can be confirmed via amino acid sequencing.

In cases where large amounts of a polypeptide are desired, it can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463.

The present invention also encompasses polypeptides encoded by the polynucleotide sequences of the present invention, as well as polypeptides according to the amino acid sequences described herein. The present invention also encompasses homologues of these polypeptides, such homologues can be at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95% or more say 100% homologous to the amino acid sequences set forth below, as can be determined using BlastP software of the National Center of Biotechnology Information (NCBI) using default parameters, optionally and preferably including the following: filtering on (this option filters repetitive or low-complexity sequences from the query using the Seg (protein) program), scoring matrix is BLOSUM62 for proteins, word size is 3, E value is 10, gap costs are 11, 1 (initialization and extension), and number of alignments shown is 50. Finally, the present invention also encompasses fragments of the above described polypeptides and polypeptides having mutations, such as deletions, insertions or substitutions of one or more amino acids, either naturally occurring or artificially induced, either randomly or in a targeted fashion. Homology/identity of nucleic acid sequences is preferably determined by using BlastN software of the National Center of Biotechnology Information (NCBI) using default parameters, which preferably include using the DUST filter program, and also preferably include having an E value of 10, filtering low complexity sequences and a word size of 11.

It will be appreciated that peptides identified according the present invention may be degradation products, synthetic peptides or recombinant peptides as well as peptidomimetics, typically, synthetic peptides and peptoids and semipeptoids which are peptide analogs, which may have, for example, modifications rendering the peptides more stable while in a body or more capable of penetrating into cells. Such modifications include, but are not limited to N terminus modification, C terminus modification, peptide bond modification, including, but not limited to, CH2-NH, CH2-S, CH2-S═O, O═C—NH, CH2-O, CH2-CH2, S═C—NH, CH═CH or CF═CH, backbone modifications, and residue modification. Methods for preparing peptidomimetic compounds are well known in the art and are specified. Further details in this respect are provided hereinunder.

Peptide bonds (—CO—NH—) within the peptide may be substituted, for example, by N-methylated bonds (—N(CH3)-CO—), ester bonds (—C(R)H—C—O—O—C(R)—N—), ketomethylen bonds (—CO—CH2-), α-aza bonds (—NH—N(R)—CO—), wherein R is any alkyl, e.g., methyl, carba bonds (—CH2-NH—), hydroxyethylene bonds (—CH(OH)—CH2-), thioamide bonds (—CS—NH—), olefinic double bonds (—CH═CH—), retro amide bonds (—NH—CO—), peptide derivatives (—N(R)—CH2-CO—), wherein R is the “normal” side chain, naturally presented on the carbon atom.

These modifications can occur at any of the bonds along the peptide chain and even at several (2-3) at the same time.

Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted for synthetic non-natural acid such as Phenylglycine, TIC, naphthylelanine (Nol), ring-methylated derivatives of Phe, halogenated derivatives of Phe or o-methyl-Tyr.

In addition to the above, the peptides of the present invention may also include one or more modified amino acids or one or more non-amino acid monomers (e.g. fatty acids, complex carbohydrates etc).

As used herein in the specification and in the claims section below the term “amino acid” or “amino acids” is understood to include the 20 naturally occurring amino acids; those amino acids often modified post-translationally in vivo, including, for example, hydroxyproline, phosphoserine and phosphothreonine; and other unusual amino acids including, but not limited to, 2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine, nor-leucine and ornithine. Furthermore, the term “amino acid” includes both D- and L-amino acids.

Table 1 non-conventional or modified amino acids which can be used with the present invention.

TABLE 1
Non-conventional amino
acid Code Non-conventional amino acid Code
α-aminobutyric acid Abu L-N-methylalanine Nmala
α-amino-α-methylbutyrate Mgabu L-N-methylarginine Nmarg
aminocyclopropane- Cpro L-N-methylasparagine Nmasn
Carboxylate L-N-methylaspartic acid Nmasp
aminoisobutyric acid Aib L-N-methylcysteine Nmcys
aminonorbornyl- Norb L-N-methylglutamine Nmgin
Carboxylate L-N-methylglutamic acid Nmglu
Cyclohexylalanine Chexa L-N-methylhistidine Nmhis
Cyclopentylalanine Cpen L-N-methylisolleucine Nmile
D-alanine Dal L-N-methylleucine Nmleu
D-arginine Darg L-N-methyllysine Nmlys
D-aspartic acid Dasp L-N-methylmethionine Nmmet
D-cysteine Dcys L-N-methylnorleucine Nmnle
D-glutamine Dgln L-N-methylnorvaline Nmnva
D-glutamic acid Dglu L-N-methylornithine Nmorn
D-histidine Dhis L-N-methylphenylalanine Nmphe
D-isoleucine Dile L-N-methylproline Nmpro
D-leucine Dleu L-N-methylserine Nmser
D-lysine Dlys L-N-methylthreonine Nmthr
D-methionine Dmet L-N-methyltryptophan Nmtrp
D-ornithine Dorn L-N-methyltyrosine Nmtyr
D-phenylalanine Dphe L-N-methylvaline Nmval
D-proline Dpro L-N-methylethylglycine Nmetg
D-serine Dser L-N-methyl-t-butylglycine Nmtbug
D-threonine Dthr L-norleucine Nle
D-tryptophan Dtrp L-norvaline Nva
D-tyrosine Dtyr α-methyl-aminoisobutyrate Maib
D-valine Dval α-methyl-γ-aminobutyrate Mgabu
D-α-methylalanine Dmala α-methylcyclohexylalanine Mchexa
D-α-methylarginine Dmarg α-methylcyclopentylalanine Mcpen
D-α-methylasparagine Dmasn α-methyl-α-napthylalanine Manap
D-α-methylaspartate Dmasp α-methylpenicillamine Mpen
D-α-methylcysteine Dmcys N-(4-aminobutyl)glycine Nglu
D-α-methylglutamine Dmgln N-(2-aminoethyl)glycine Naeg
D-α-methylhistidine Dmhis N-(3-aminopropyl)glycine Norn
D-α-methylisoleucine Dmile N-amino-α-methylbutyrate Nmaabu
D-α-methylleucine Dmleu α-napthylalanine Anap
D-α-methyllysine Dmlys N-benzylglycine Nphe
D-α-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln
D-α-methylornithine Dmorn N-(carbamylmethyl)glycine Nasn
D-α-methylphenylalanine Dmphe N-(2-carboxyethyl)glycine Nglu
D-α-methylproline Dmpro N-(carboxymethyl)glycine Nasp
D-α-methylserine Dmser N-cyclobutylglycine Ncbut
D-α-methylthreonine Dmthr N-cycloheptylglycine Nchep
D-α-methyltryptophan Dmtrp N-cyclohexylglycine Nchex
D-α-methyltyrosine Dmty N-cyclodecylglycine Ncdec
D-α-methylvaline Dmval N-cyclododeclglycine Ncdod
D-α-methylalnine Dnmala N-cyclooctylglycine Ncoct
D-α-methylarginine Dnmarg N-cyclopropylglycine Ncpro
D-α-methylasparagine Dnmasn N-cycloundecylglycine Ncund
D-α-methylasparatate Dnmasp N-(2,2-diphenylethyl)glycine Nbhm
D-α-methylcysteine Dnmcys N-(3,3- Nbhe
diphenylpropyl)glycine
D-N-methylleucine Dnmleu N-(3-indolylyethyl) glycine Nhtrp
D-N-methyllysine Dnmlys N-methyl-Îł-aminobutyrate Nmgabu
N- Nmchexa D-N-methylmethionine Dnmmet
methylcyclohexylalanine
D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen
N-methylglycine Nala D-N-methylphenylalanine Dnmphe
N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro
N-(1-methylpropyl)glycine Nile D-N-methylserine Dnmser
N-(2-methylpropyl)glycine Nile D-N-methylserine Dnmser
N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr
D-N-methyltryptophan Dnmtrp N-(1-methylethyl)glycine Nva
D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap
D-N-methylvaline Dnmval N-methylpenicillamine Nmpen
Îł-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr
L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys
L-ethylglycine Etg penicillamine Pen
L-homophenylalanine Hphe L-α-methylalanine Mala
L-α-methylarginine Marg L-α-methylasparagine Masn
L-α-methylaspartate Masp L-α-methyl-t-butylglycine Mtbug
L-α-methylcysteine Mcys L-methylethylglycine Metg
L-α-methylglutamine Mgln L-α-methylglutamate Mglu
L-α-methylhistidine Mhis L-α-methylhomo Mhphe
phenylalanine
L-α-methylisoleucine Mile N-(2-methylthioethyl)glycine Nmet
D-N-methylglutamine Dnmgln N-(3- Narg
guanidinopropyl)glycine
D-N-methylglutamate Dnmglu N-(1-hydroxyethyl)glycine Nthr
D-N-methylhistidine Dnmhis N-(hydroxyethyl)glycine Nser
D-N-methylisoleucine Dnmile N-(imidazolylethyl)glycine Nhis
D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycine Nhtrp
D-N-methyllysine Dnmlys N-methyl-Îł-aminobutyrate Nmgabu
N- Nmchexa D-N-methylmethionine Dnmmet
methylcyclohexylalanine
D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen
N-methylglycine Nala D-N-methylphenylalanine Dnmphe
N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro
N-(1-methylpropyl)glycine Nile D-N-methylserine Dnmser
N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr
D-N-methyltryptophan Dnmtrp N-(1-methylethyl)glycine Nval
D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap
D-N-methylvaline Dnmval N-methylpenicillamine Nmpen
Îł-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr
L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys
L-ethylglycine Etg penicillamine Pen
L-homophenylalanine Hphe L-α-methylalanine Mala
L-α-methylarginine Marg L-α-methylasparagine Masn
L-α-methylaspartate Masp L-α-methyl-t-butylglycine Mtbug
L-α-methylcysteine Mcys L-methylethylglycine Metg
L-α-methylglutamine Mgln L-α-methylglutamate Mglu
L-α-methylhistidine Mhis L-α- Mhphe
methylhomophenylalanine
L-α-methylisoleucine Mile N-(2-methylthioethyl)glycine Nmet
L-α-methylleucine Mleu L-α-methyllysine Mlys
L-α-methylmethionine Mmet L-α-methylnorleucine Mnle
L-α-methylnorvaline Mnva L-α-methylornithine Morn
L-α-methylphenylalanine Mphe L-α-methylproline Mpro
L-α-methylserine mser L-α-methylthreonine Mthr
L-α-methylvaline Mtrp L-α-methyltyrosine Mtyr
L-α-methylleucine Mval L-N- Nmhphe
Nnbhm methylhomophenylalanine
N-(N-(2,2-diphenylethyl) N-(N-(3,3-diphenylpropyl)
carbamylmethyl-glycine Nnbhm carbamylmethyl(1)glycine Nnbhe
1-carboxy-1-(2,2-diphenylethylamino) Nmbc
cyclopropane

Since the peptides of the present invention are preferably utilized in diagnostics which require the peptides to be in soluble form, the peptides of the present invention preferably include one or more non-natural or natural polar amino acids, including but not limited to serine and threonine which are capable of increasing peptide solubility due to their hydroxyl-containing side chain.

The peptides of the present invention are preferably utilized in a linear form, although it will be appreciated that in cases where cyclicization does not severely interfere with peptide characteristics, cyclic forms of the peptide can also be utilized.

The peptides of present invention can be biochemically synthesized such as by using standard solid phase techniques. These methods include exclusive solid phase synthesis well known in the art, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry.

Synthetic peptides can be purified by preparative high performance liquid chromatography and the composition of which can be confirmed via amino acid sequencing.

In cases where large amounts of the peptides of the present invention are desired, the peptides of the present invention can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463 and also as described above.

Antibodies

“Antibody” refers to a polypeptide ligand that is preferably substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, which specifically binds and recognizes an epitope (e.g., an antigen). The recognized immunoglobulin genes include the kappa and lambda light chain constant region genes, the alpha, gamma, delta, epsilon and mu heavy chain constant region genes, and the myriad-immunoglobulin variable region genes. Antibodies exist, e.g., as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. This includes, e.g., Fabâ€Č and F(ab)â€Č2 fragments. The term “antibody,” as used herein, also includes antibody fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies. It also includes polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, or single chain antibodies. “Fc” portion of an antibody refers to that portion of an immunoglobulin heavy chain that comprises one or more heavy chain constant region domains, CH1, CH2 and CH3, but does not include the heavy chain variable region.

The functional fragments of antibodies, such as Fab, F(abâ€Č)2, and Fv that are capable of binding to macrophages, are described as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fabâ€Č, the fragment of an antibody molecule that can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fabâ€Č fragments are obtained per antibody molecule; (3) (Fabâ€Č)2, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(abâ€Č)2 is a dimer of two Fabâ€Č fragments held together by two disulfide bonds; (4) Fv, defined as a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (5) Single chain antibody (“SCA”), a genetically engineered molecule containing the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule.

Methods of producing polyclonal and monoclonal antibodies as well as fragments thereof are well known in the art (See for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988, incorporated herein by reference).

Antibody fragments according to the present invention can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli or mammalian cells (e.g. Chinese hamster ovary cell culture or other protein expression systems) of DNA encoding the fragment. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(abâ€Č)2. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fabâ€Č monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fabâ€Č fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647, and references contained therein, which patents are hereby incorporated by reference in their entirety. See also Porter, R. R. [Biochem. J. 73: 119-126 (1959)]. Other methods of cleaving antibodies, such as separation of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody.

Fv fragments comprise an association of VH and VL chains. This association may be noncovalent, as described in Inbar et al. [Proc. Nat'l Acad. Sci. USA 69:2659-62 (19720]. Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross-linked by chemicals such as glutaraldehyde. Preferably, the Fv fragments comprise VH and VL chains connected by a peptide linker. These single-chain antigen binding proteins (sFv) are prepared by constructing a structural gene comprising DNA sequences encoding the VH and VL domains connected by an oligonucleotide. The structural gene is inserted into an expression vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing sFvs are described, for example, by [Whitlow and Filpula, Methods 2: 97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et al., Bio/Technology 11:1271-77 (1993); and U.S. Pat. No. 4,946,778, which is hereby incorporated by reference in its entirety.

Another form of an antibody fragment is a peptide coding for a single complementarity-determining region (CDR). CDR peptides (“minimal recognition units”) can be obtained by constructing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from RNA of antibody-producing cells. See, for example, Larrick and Fry [Methods, 2: 106-10 (1991)].

Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fabâ€Č, F(abâ€Č) or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)].

Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991)]. Similarly, human antibodies can be made by introduction of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10,: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368 812-13 (1994); Fishwild et al., Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and-Lonberg and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995).

Preferably, the antibody of this aspect of the present invention specifically binds at least one epitope of the polypeptide variants of the present invention. As used herein, the term “epitope” refers to any antigenic determinant on an antigen to which the paratope of an antibody binds.

Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics.

Optionally, a unique epitope may be created in a variant due to a change in one or more post-translational modifications, including but not limited to glycosylation and/or phosphorylation, as described below. Such a change may also cause a new epitope to be created, for example through removal of glycosylation at a particular site.

An epitope according to the present invention may also optionally comprise part or all of a unique sequence portion of a variant according to the present invention in combination with at least one other portion of the variant which is not contiguous to the unique sequence portion in the linear polypeptide itself, yet which are able to form an epitope in combination. One or more unique sequence portions may optionally combine with one or more other non-contiguous portions of the variant (including a portion which may have high homology to a portion of the known protein) to form an epitope.

Immunoassays

In another embodiment of the present invention, an immunoassay can be used to qualitatively or quantitatively detect and analyze markers in a sample. This method comprises: providing an antibody that specifically binds to a marker; contacting a sample with the antibody; and detecting the presence of a complex of the antibody bound to the marker in the sample.

To prepare an antibody that specifically binds to a marker, purified protein markers can be used. Antibodies that specifically bind to a protein marker can be prepared using any suitable methods known in the art.

After the antibody is provided, a marker can be detected and/or quantified using any of a number of well recognized immunological binding assays. Useful assays include, for example, an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay (ELISA), a radioimmune assay (RIA), a Western blot assay, or a slot blot assay see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). Generally, a sample obtained from a subject can be contacted with the antibody that specifically binds the marker.

Optionally, the antibody can be fixed to a solid support to facilitate washing and subsequent isolation of the complex, prior to contacting the antibody with a sample. Examples of solid supports include but are not limited to glass or plastic in the form of, e.g., a microtiter plate, a stick, a bead, or a microbead. Antibodies can also be attached to a solid support.

After incubating the sample with antibodies, the mixture is washed and the antibody-marker complex formed can be detected. This can be accomplished by incubating the washed mixture with a detection reagent. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.

Throughout the assays, incubation and/or washing steps may be required after each combination of reagents. Incubation steps can vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time will depend upon the assay format, marker, volume of solution, concentrations and the like. Usually the assays will be carried out at ambient temperature, although they can be conducted over a range of temperatures, such as 10° C. to 40° C.

The immunoassay can be used to determine a test amount of a marker in a sample from a subject. First, a test amount of a marker in a sample can be detected using the immunoassay methods described above. If a marker is present in the sample, it will form an antibody-marker complex with an antibody that specifically binds the marker under suitable incubation conditions described above. The amount of an antibody-marker complex can optionally be determined by comparing to a standard. As noted above, the test amount of marker need not be measured in absolute units, as long as the unit of measurement can be compared to a control amount and/or signal.

Preferably used are antibodies which specifically interact with the polypeptides of the present invention and not with wild type proteins or other isoforms thereof, for example. Such antibodies are directed, for example, to the unique sequence portions of the polypeptide variants of the present invention, including but not limited to bridges, heads, tails and insertions described in greater detail below. Preferred embodiments of antibodies according to the present invention are described in greater detail with regard to the section entitled “Antibodies”.

Radio-immunoassay (RIA): In one version, this method involves precipitation of the desired substrate and in the methods detailed hereinbelow, with a specific antibody and radiolabelled antibody binding protein (e.g., protein A labeled with I125) immobilized on a precipitable carrier such as agarose beads. The number of counts in the precipitated pellet is proportional to the amount of substrate.

In an alternate version of the RIA, a labeled substrate and an unlabelled antibody binding protein are employed. A sample containing an unknown amount of substrate is added in varying amounts. The decrease in precipitated counts from the labeled substrate is proportional to the amount of substrate in the added sample.

Enzyme linked immunosorbent assay (ELISA): This method involves fixation of a sample (e.g., fixed cells or a proteinaceous solution) containing a protein substrate to a surface such as a well of a microtiter plate. A substrate specific antibody coupled to an enzyme is applied and allowed to bind to the substrate. Presence of the antibody is then detected and quantitated by a colorimetric reaction employing the enzyme coupled to the antibody. Enzymes commonly employed in this method include horseradish peroxidase and alkaline phosphatase. If well calibrated and within the linear range of response, the amount of substrate present in the sample is proportional to the amount of color produced. A substrate standard is generally employed to improve quantitative accuracy.

Western blot: This method involves separation of a substrate from other protein by means of an acrylamide gel followed by transfer of the substrate to a membrane (e.g., nylon or PVDF). Presence of the substrate is then detected by antibodies specific to the substrate, which are in turn detected by antibody binding reagents. Antibody binding reagents may be, for example, protein A, or other antibodies. Antibody binding reagents may be radiolabelled or enzyme linked as described hereinabove. Detection may be by autoradiography, colorimetric reaction or chemiluminescence. This method allows both quantitation of an amount of substrate and determination of its identity by a relative position on the membrane which is indicative of a migration distance in the acrylamide gel during electrophoresis.

Immunohistochemical analysis: This method involves detection of a substrate in situ in fixed cells by substrate specific antibodies. The substrate specific antibodies may be enzyme linked or linked to fluorophores. Detection is by microscopy and subjective evaluation. If enzyme linked antibodies are employed, a colorimetric reaction may be required.

Fluorescence activated cell sorting (FACS): This method involves detection of a substrate in situ in cells by substrate specific antibodies. The substrate specific antibodies are linked to fluorophores. Detection is by means of a cell sorting machine which reads the wavelength of light emitted from each cell as it passes through a light beam. This method may employ two or more antibodies simultaneously.

Radio-Imaging Methods

These methods include but are not limited to, positron emission tomography (PET) single photon emission computed tomography (SPECT). Both of these techniques are non-invasive, and can be used to detect and/or measure a wide variety of tissue events and/or functions, such as detecting cancerous cells for example. Unlike PET, SPECT can optionally be used with two labels simultaneously. SPECT has some other advantages as well, for example with regard to cost and the types of labels that can be used. For example, US Patent No. 6,696,686 describes the use of SPECT for detection of breast cancer, and is hereby incorporated by reference as if fully set forth herein.

Display Libraries

According to still another aspect of the present invention there is provided a display library comprising a plurality of display vehicles (such as phages, viruses or bacteria) each displaying at least 6, at least 7, at least 8, at least 9, at least 10, 10-15, 12-17, 15-20, 15-30 or 20-50 consecutive amino acids derived from the polypeptide sequences of the present invention.

Methods of constructing such display libraries are well known in the art. Such methods are described in, for example, Young A C, et al., “The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes” J Mol Biol Dec. 12, 1997;274(4):622-34; Giebel L B et al. “Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities” Biochemistry Nov. 28, 1995;34(47):15430-5; Davies E L et al., “Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes” J Immunol Methods Oct. 12, 1995;186(l):125-35; Jones C R T al. “Current trends in molecular recognition and bioseparation” J Chromatogr A Jul. 14, 1995;707(1):3-22; Deng S J et al. “Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries” Proc Natl Acad Sci USA May 23, 1995;92(11):4992-6; and Deng S J et al. “Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display” J Biol Chem Apr. 1, 1994;269(13):9533-8, which are incorporated herein by reference.

The following sections relate to Candidate Marker Examples (first section) and to Experimental Data for these Marker Examples (second section).

CANDIDATE MARKER EXAMPLES SECTION

This Section relates to Examples of sequences according to the present invention, including illustrative methods of selection thereof.

DESCRIPTION OF THE METHODOLOGY UNDERTAKEN TO UNCOVER THE BIOMOLECULAR SEQUENCES OF THE PRESENT INVENTION

Human ESTs and cDNAs were obtained from GenBank versions 136 (Jun. 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gb136.release.notes); NCBI genome assembly of April 2003; RefSeq sequences from June 2003; Genbank version 139 (December 2003); Human Genome from NCBI (Build 34) (from October 2003); RefSeq sequences from December 2003; and from LifeSeq library of Incyte Corp (Wilmington, Del., USA; ESTs only). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section and the human mRNA sequences from the primate (GBPRI) section were used; also the human nucleotide RefSeq mRNA sequences were used (see for example www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html and for a reference to the EST section, see www.ncbi.nlm.nih.gov/dbEST/; a general reference to dbEST, the EST database in GenBank, may be found in Boguski et al, Nat Genet. 1993 Aug.;4(4):332-3; all of which are hereby incorporated by reference as if fully set forth herein).

Novel splice variants were predicted using the LEADS clustering and assembly system as described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); U.S. Pat. No: 6,625,545; and U.S. patent application Ser. No. 10/426,002, published as US20040101876 on May 27 2004; all of which are hereby incorporated by reference as if fully set forth herein. Briefly, the software cleans the expressed sequences from repeats, vectors and immunoglobulins. It then aligns the expressed sequences to the genome taking alternatively splicing into account and clusters overlapping expressed sequences into “clusters” that represent genes or partial genes.

These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel) platform. The GeneCarta platform includes a rich pool of annotations, sequence information (particularly of spliced sequences), chromosomal information, alignments, and additional information such as SNPs, gene ontology terms, expression profiles, functional analyses, detailed domain structures, known and predicted proteins and detailed homology reports.

A brief explanation is provided with regard to the method of selecting the candidates. However, it should noted that this explanation is provided for descriptive purposes only, and is not intended to be limiting in any way. The potential markers were identified by a computational process that was designed to find genes and/or their splice variants that are over-expressed in tumor tissues, by using databases of expressed sequences. Various parameters related to the information in the EST libraries, determined according to a manual classification process, were used to assist in locating genes and/or splice variants thereof that are over-expressed in cancerous tissues. The detailed description of the selection method is presented in Example 1 below. The cancer biomarkers selection engine and the following wet validation stages are schematically summarized in FIG. 1.

EXAMPLE 1 Identification of Differentially Expressed Gene Products—Algorithm

In order to distinguish between differentially expressed gene products and constitutively expressed genes (i.e., house keeping genes ) an algorithm based on an analysis of frequencies was configured. A specific algorithm for identification of transcripts over expressed in cancer is described hereinbelow.

Dry Analysis

Library annotation—EST libraries are manually classified according to:

    • (i) Tissue origin
    • (ii) Biological source—Examples of frequently used biological sources for construction of EST libraries include cancer cell-lines; normal tissues; cancer tissues; fetal tissues; and others such as normal cell lines and pools of normal cell-lines, cancer cell-lines and combinations thereof. A specific description of abbreviations used below with regard to these tissues/cell lines etc is given above.
    • (iii) Protocol of library construction—various methods are known in the art for library construction including normalized library construction; non-normalized library construction; subtracted libraries; ORESTES and others. It will be appreciated that at times the protocol of library construction is not indicated.

The following rules were followed:

EST libraries originating from identical biological samples are considered as a single library.

EST libraries which included above-average levels of contamination, such as DNA contamination for example, were eliminated. The presence of such contamination was determined as follows. For each library, the number of unspliced ESTs that are not fully contained within other spliced sequences was counted. If the percentage of such sequences (as compared to all other sequences) was at least 4 standard deviations above the average for all libraries being analyzed, this library was tagged as being contaminated and was eliminated from further consideration in the below analysis (see also Sorek, R. & Safer, H. M. A novel algorithm for computational identification of contaminated EST libraries. Nucleic Acids Res 31, 1067-74 (2003)for further details).

Clusters (genes) having at least five sequences including at least two sequences from the tissue of interest were analyzed. Splice variants were identified by using the LEADS software package as described above.

EXAMPLE 2 Identification of Genes Over Expressed in Cancer

Two different scoring algorithms were developed.

Libraries score—candidate sequences which are supported by a number of cancer libraries, are more likely to serve as specific and effective diagnostic markers.

The basic algorithm—for each cluster the number of cancer and normal libraries contributing sequences to the cluster was counted. Fisher exact test was used to check if cancer libraries are significantly over-represented in the cluster as compared to the total number of cancer and normal libraries.

Library counting: Small libraries (e.g., less than 1000 sequences) were excluded from consideration unless they participate in the cluster. For this reason, the total number of libraries is actually adjusted for each cluster.

Clones no. score—Generally, when the number of ESTs is much higher in the cancer libraries relative to the normal libraries it might indicate actual over-expression.

The algorithm—

Clone counting: For counting EST clones each library protocol class was given a weight based on our belief of how much the protocol reflects actual expression levels:

(i) non-normalized: 1

(ii) normalized: 0.2

(iii) all other classes: 0.1

Clones number score—The total weighted number of EST clones from cancer libraries was compared to the EST clones from normal libraries. To avoid cases where one library contributes to the majority of the score, the contribution of the library that gives most clones for a given cluster was limited to 2 clones.

The score was computed as c + 1 C / n + 1 N
where:

c—weighted number of “cancer” clones in the cluster.

C—weighted number of clones in all “cancer” libraries.

n—weighted number of “normal” clones in the cluster.

N—weighted number of clones in all “normal” libraries.

Clones number score significance—Fisher exact test was used to check if EST clones from cancer libraries are significantly over-represented in the cluster as compared to the total number of EST clones from cancer and normal libraries.

Two search approaches were used to find either general cancer-specific candidates or tumor specific candidates.

    • Libraries/sequences originating from tumor tissues are counted as well as libraries originating from cancer cell-lines (“normal” cell-lines were ignored).
    • Only libraries/sequences originating from tumor tissues are counted
EXAMPLE 3 Identification of tissue Specific Genes

For detection of tissue specific clusters, tissue libraries/sequences were compared to the total number of libraries/sequences in cluster. Similar statistical tools to those described in above were employed to identify tissue specific genes. Tissue abbreviations are the same as for cancerous tissues, but are indicated with the header “normal tissue”.

The algorithm—for each tested tissue T and for each tested cluster the following were examined:

1. Each cluster includes at least 2 libraries from the tissue T. At least 3 clones (weighed—as described above) from tissue T in the cluster; and

2. Clones from the tissue T are at least 40% from all the clones participating in the tested cluster

Fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant.

EXAMPLE 4 Identification of Splice Variants Expressed in Cancer of Clusters Which are Not Over Expressed in Cancer

Cancer-Specific Splice Variants Containing a Unique Region were Identified.

Identification of unique sequence regions in splice variants A Region is defined as a group of adjacent exons that always appear or do not appear together in each splice variant.

A “segment” (sometimes referred also as “seg” or “node”) is defined as the shortest contiguous transcribed region without known splicing inside.

Only reliable ESTs were considered for region and segment analysis. An EST was defined as unreliable if:

(i) Unspliced;

(ii) Not covered by RNA;

(iii) Not covered by spliced ESTs; and

(iv) Alignment to the genome ends in proximity of long poly-A stretch or starts in proximity of long poly-T stretch.

Only reliable regions were selected for further scoring. Unique sequence regions were considered reliable if:

(i) Aligned to the genome; and

(ii) Regions supported by more than 2 ESTs.

The algorithm

Each unique sequence region divides the set of transcripts into 2 groups:

(i) Transcripts containing this region (group TA).

(ii) Transcripts not containing this region (group TB).

The set of EST clones of every cluster is divided into 3 groups:

(i) Supporting (originating from) transcripts of group TA (S1).

(ii) Supporting transcripts of group TB (S2).

(iii) Supporting transcripts from both groups (S3).

Library and clones number scores described above were given to S1 group.

Fisher Exact Test P-values were used to check if:

S1 is significantly enriched by cancer EST clones compared to S2; and

S1 is significantly enriched by cancer EST clones compared to cluster background (S1+S2+S3).

Identification of unique sequence regions and division of the group of transcripts accordingly is illustrated in FIG. 2. Each of these unique sequence regions corresponds to a segment, also termed herein a “node”.

Region 1: common to all transcripts, thus it is preferably not considered for determining differential expression between variants; Region 2: specific to Transcript 1; Region 3: specific to Transcripts 2+3; Region 4: specific to Transcript 3; Region 5: specific to Transcripts 1 and 2; Region 6: specific to Transcript 1.

EXAMPLE 5 Identification of Cancer Specific Splice Variants of Genes Over Expressed in Cancer

A search for EST supported (no mRNA) regions for genes of:

(i) known cancer markers

(ii) Genes shown to be over-expressed in cancer in published micro-array experiments.

Reliable EST supported-regions were defined as supported by minimum of one of the following:

(i) 3 spliced ESTs; or

(ii) 2 spliced ESTs from 2 libraries;

(iii) 10 unspliced ESTs from 2 libraries, or

(iv) 3 libraries.

ACTUAL MARKER EXAMPLES

The following examples relate to specific actual marker examples.

EXPERIMENTAL EXAMPLES SECTION

This Section relates to Examples describing experiments involving these sequences, and illustrative, non-limiting examples of methods, assays and uses thereof. The materials and experimental procedures are explained first, as all experiments used them as a basis for the work that was performed.

The markers of the present invention were tested with regard to their expression in various cancerous and non-cancerous tissue samples. A description of the samples used in the panel is provided in Table 1 below. A description of the samples used in the normal tissue panel is provided in Table 2 below. Tests were then performed as described in the “Materials and Experimental Procedures” section below.

TABLE 1
Tissue samples in testing panel
sample sex/
rename Lot no source pathology grade age TNM stage
52-B-ILC G1 A605360 Biochain Invasive 1 F/60
Lobular
Carcinoma
51-B-IDC G1 A605361 Biochain IDC 1 F/79
6-A-IDC G1 7238T ABS IDC 1 F/60 T2N0M0 stage
2A
7-A-IDC G2 7263T ABS IDC 2 F/43 T1N0M0 stage 1
12-A-IDC G2 1432T ABS IDC 2 F/46 T2N0M0 stage
2A
13-A-IDC G2 A0133T ABS IDC 2 F/63 T2N1a
Mx
14-A-IDC G2 A0135T ABS IDC 2 F/37 T2N2Mx
15-A-IDC G2 7259T ABS IDC 2 F/59 T3N1M0 stage
3A
16-A-IDC G2 4904020032T ABS IDC 2 NA T3N1Mx
17-A-IDC G2 4904020036T ABS IDC 2-3 NA T3N1Mx
43-B-IDC G2 A609183 Biochain IDC 2 F/40
44-B-IDC G2 A609198 Biochain IDC 2 F/77
45-B-IDC G2 A609181 Biochain IDC 2 F/58
48-B-IDC G2 A609222 Biochain IDC 2 F/44
49-B-IDC G2 A609223 Biochain IDC 2 F/54
50-B-IDC G2 A609224 Biochain IDC 2 F/69
53-B-IDC G2 A605151 Biochain IDC 2 F/44
54-B-IDC G2 A605353 Biochain IDC 2 F/41
55-B-IDC G2 A609179 Biochain IDC 2 F/42
61-B-IDC G2 A610029 Biochain IDC 2 F/46
62-B-IDC G2 A609194 Biochain IDC 2 F/51
47-B-IDC G2 A609221 Biochain IDC 2
46-B-Carci G2 A609177 Biochain Carcinoma 2 F/48
26-A-IDC G3 7249T ABS IDC 3 F/60 T2N0M0 stage
2A
27-A-IDC G3 4907020072T ABS IDC 3 NA T2N0Mx
42-A-IDC G3 6005020031T ABS IDC 3 NA T1cN0
Mx
31-CG-IDC CG-154 Ichilov IDC NA
32-A-Muc 7116T ABS Mucinous F/54 T2N0M0 stage
Carci carcinoma 2A
35-A-N M6 7238N ABS Normal F/60
matched
to 6T
36-A-N M7 7263N ABS Normal F/43
matched
to 7T
39-A-N M15 7259N ABS Normal F/59
matched
to 15T
40-A-N M12 1432N ABS Normal F/46
matched
to 12T
41-A-N M26 7249N ABS Normal F/60
matched
to 26T
56-B-N A609235 Biochain Normal F/59
PM
57-B-N A609233 Biochain Normal F/34
PM
58-B-N A609232 Biochain Normal F/65
PM
59-B-N A607155 Biochain Normal F/35
PM
60-B-N A609234 Biochain Normal F/36
PM
63-Am-N 26486 Ambion Normal PS F/43
64-Am-N 23036 Ambion Normal F/57
PM
65-Am-N 31410 Ambion Normal F/63
PM
66-Am-N 36678 Ambion Normal F/45
PM
67-Am-N 073P010602086A Ambion Normal F/64
PM

TABLE 2
Tissue samples in normal panel:
Lot no. Source Tissue Pathology Sex/Age
 1-Am-Colon (C71) 071P10B Ambion Colon PM F/43
 2-B-Colon (C69) A411078 Biochain Colon PM-Pool of 10 M&F
 3-Cl-Colon (C70) 1110101 Clontech Colon PM-Pool of 3 M&F
 4-Am-Small Intestine 091P0201A Ambion Small Intestine PM M/75
 5-B-Small Intestine A501158 Biochain Small Intestine PM M/63
 6-B-Rectum A605138 Biochain Rectum PM M/25
 7-B-Rectum A610297 Biochain Rectum PM M/24
 8-B-Rectum A610298 Biochain Rectum PM M/27
 9-Am-Stomach 110P04A Ambion Stomach PM M/16
10-B-Stomach A501159 Biochain Stomach PM M/24
11-B-Esophagus A603814 Biochain Esophagus PM M/26
12-B-Esophagus A603813 Biochain Esophagus PM M/41
13-Am-Pancreas 071P25C Ambion Pancreas PM M/25
14-CG-Pancreas CG-255-2 Ichilov Pancreas PM M/75
15-B-Lung A409363 Biochain Lung PM F/26
16-Am-Lung (L93) 111P0103A Ambion Lung PM F/61
17-B-Lung (L92) A503204 Biochain Lung PM M/28
18-Am-Ovary (O47) 061P43A Ambion Ovary PM F/16
19-B-Ovary (O48) A504087 Biochain Ovary PM F/51
20-B-Ovary (O46) A504086 Biochain Ovary PM F/41
21-Am-Cervix 101P0101A Ambion Cervix PM F/40
22-B-Cervix A408211 Biochain Cervix PM F/36
23-B-Cervix A504089 Biochain Cervix PM-Pool of 5 M&F
24-B-Uterus A411074 Biochain Uterus PM-Pool of 10 M&F
25-B-Uterus A409248 Biochain Uterus PM F/43
26-B-Uterus A504090 Biochain Uterus PM-Pool of 5 M&F
27-B-Bladder A501157 Biochain Bladder PM M/29
28-Am-Bladder 071P02C Ambion Bladder PM M/20
29-B-Bladder A504088 Biochain Bladder PM-Pool of 5 M&F
30-Am-Placenta 021P33A Ambion Placenta PB F/33
31-B-Placenta A410165 Biochain Placenta PB F/26
32-B-Placenta A411073 Biochain Placenta PB-Pool of 5 M&F
33-B-Breast (B59) A607155 Biochain Breast PM F/36
34-Am-Breast (B63) 26486 Ambion Breast PM F/43
35-Am-Breast (B64) 23036 Ambion Breast PM F/57
36-Cl-Prostate (P53) 1070317 Clontech Prostate PB-Pool of 47 M&F
37-Am-Prostate (P42) 061P04A Ambion Prostate PM M/47
38-Am-Prostate (P59) 25955 Ambion Prostate PM M/62
39-Am-Testis 111P0104A Ambion Testis PM M/25
40-B-Testis A411147 Biochain Testis PM M/74
41-Cl-Testis 1110320 Clontech Testis PB-Pool of 45 M&F
42-CG-Adrenal CG-184-10 Ichilov Adrenal PM F/81
43-B-Adrenal A610374 Biochain Adrenal PM F/83
44-B-Heart A411077 Biochain Heart PB-Pool of 5 M&F
45-CG-Heart CG-255-9 Ichilov Heart PM M/75
46-CG-Heart CG-227-1 Ichilov Heart PM F/36
47-Am-Liver 081P0101A Ambion Liver PM M/64
48-CG-Liver CG-93-3 Ichilov Liver PM F/19
49-CG-Liver CG-124-4 Ichilov Liver PM F/34
50-Cl-BM 1110932 Clontech Bone Marrow PM-Pool of 8 M&F
51-CGEN-Blood WBC#5 CGEN Blood M
52-CGEN-Blood WBC#4 CGEN Blood M
53-CGEN-Blood WBC#3 CGEN Blood M
54-CG-Spleen CG-267 Ichilov Spleen PM F/25
55-CG-Spleen 111P0106B Ambion Spleen PM M/25
56-CG-Spleen A409246 Biochain Spleen PM F/12
56-CG-Thymus CG-98-7 Ichilov Thymus PM F/28
58-Am-Thymus 101P0101A Ambion Thymus PM M/14
59-B-Thymus A409278 Biochain Thymus PM M/28
60-B-Thyroid A610287 Biochain Thyroid PM M/27
61-B-Thyroid A610286 Biochain Thyroid PM M/24
62-CG-Thyroid CG-119-2 Ichilov Thyroid PM F/66
63-Cl-Salivary Gland 1070319 Clontech Salivary Gland PM-Pool of 24 M&F
64-Am-Kidney 111P0101B Ambion Kidney PM-Pool of 14 M&F
65-Cl-Kidney 1110970 Clontech Kidney PM-Pool of 14 M&F
66-B-Kidney A411080 Biochain Kidney PM-Pool of 5 M&F
67-CG-Cerebellum CG-183-5 Ichilov Cerebellum PM M/74
68-CG-Cerebellum CG-212-5 Ichilov Cerebellum PM M/54
69-B-Brain A411322 Biochain Brain PM M/28
70-Cl-Brain 1120022 Clontech Brain PM-Pool of 2 M&F
71-B-Brain A411079 Biochain Brain PM-Pool of 2 M&F
72-CG-Brain CG-151-1 Ichilov Brain PM F/86
73-Am-Skeletal Muscle 101P013A Ambion Skeletal Muscle PM F/28
74-Cl-Skeletal Muscle 1061038 Clontech Skeletal Muscle PM-Pool of 2 M&F

Materials and Experimental Procedures

RNA preparation—RNA was obtained from Clontech (Franklin Lakes, N.J. USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, Calif. 94545 USA www.biochain.com), ABS (Wilmington, Del. 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, Tex. 78744 USA, http://www.ambion.com). Alternatively, RNA was generated from tissue samples using TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion) and purified using RNeasy columns (Qiagen).

RT PCR—Purified RNA (1 ÎŒg) was mixed with 150 ng Random Hexamer primers (Invitrogen) and 500 ÎŒM dNTP in a total volume of 15.6 ÎŒl. The mixture was incubated for 5 min at 65° C. and then quickly chilled on ice. Thereafter, 5 ÎŒl of 5× SuperscriptII first strand buffer (Invitrogen), 2.4 ÎŒl 0.1M DTT and 40 units RNasin (Promega) were added, and the mixture was incubated for 10 min at 25° C., followed by further incubation at 42° C. for 2 min. Then, 1 ÎŒl (200units) of SuperscriptII (Invitrogen) was added and the reaction (final volume of 25ÎŒl) was incubated for 50 min at 42° C. and then inactivated at 70° C. for 15 min. The resulting cDNA was diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8).

Real-Time RT-PCR analysis—cDNA (5 ÎŒl), prepared as described above, was used as a template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied Biosystem) with specific primers and UNG Enzyme (Eurogentech or ABI or Roche). The amplification was effected as follows: 50° C. for 2 min, 95° C. for 10 min, and then 40 cycles of 95° C. for 15 sec, followed by 60° C. for 1 min. Detection was performed by using the PE Applied Biosystem SDS 7000. The cycle in which the reactions achieved a threshold level (Ct) of fluorescence was registered and was used to calculate the relative transcript quantity in the RT reactions. The relative quantity was calculated using the equation Q=efficiencylˆ−Ct. The efficiency of the PCR reaction was calculated from a standard curve, created by using serial dilutions of several reverse transcription (RT) reactions. To minimize inherent differences in the RT reaction, the resulting relative quantities were normalized to the geometric mean of the relative quantities of several housekeeping (HSKP) genes. Schematic summary of quantitative real-time PCR analysis is presented in FIG. 3. As shown, the x-axis shows the cycle number. The CT=Threshold Cycle point, which is the cycle that the amplification curve crosses the fluorescence threshold that was set in the experiment. This point is a calculated cycle number in which PCR product signal is above the background level (passive dye ROX) and still in the Geometric/Exponential phase (as shown, once the level of fluorescence crosses the measurement threshold, it has a geometrically increasing phase, during which measurements are most accurate, followed by a linear phase and a plateau phase; for quantitative measurements, the latter two phases do not provide accurate measurements). The y-axis shows the normalized reporter fluorescence. It should be noted that this type of analysis provides relative quantification.

The sequences of the housekeeping genes measured in all the examples on breast cancer panel were as follows:

G6PD (GenBank Accession No. NM_000402 (SEQ ID NO: 918))
G6PD Forward primer: (SEQ ID NO: 919)
gaggccgtcaccaagaacat
G6PD Reverse primer: (SEQ ID NO: 920)
ggacagccggtcagagctc
G6PD-amplicon: (SEQ ID NO: 921)
gaggccgtcaccaagaacattcacgagtcctgcatgagccagataggctggaaccgcatcatcgtggagaagcccttcgggagggacct
gcagagctctgaccggctgtcc
SDHA (GenBank Accession No. NM_004168 (SEQ ID NO: 922))
SDHA Forward primer: (SEQ ID NO: 923)
TGGGAACAAGAGGGCATCTG
SDHA reverse primer: (SEQ ID NO: 924)
CCACCACTGCATCAAATTCATG
SDHA-amplicon: (SEQ ID NO: 925)
TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT
AGTGGATCATGAATTTGATGCAGTGGTGG
PBGD (GenBank Accession No. BC019323, (SEQ ID NO: 926))
PBGD Forward primer: (SEQ ID NO: 927)
TGAGAGTGATTCGCGTGGG
PBGD Reverse primer: (SEQ ID NO: 928)
CCAGGGTACGAGGCTTTCAAT
PBGD-amplicon: (SEQ ID NO: 929)
TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAGACGGAC
AGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG
HPRT1 (GenBank Accession No. NM_000194, (SEQ ID NO: 930))
HPRT1 Forward primer: (SEQ ID NO: 931)
TGACACTGGCAAAACAATGCA
HPRT1 reverse primer: (SEQ ID NO: 932)
GGTCCTTTTCACCAGCAAGCT
HPRT1-amplicon: (SEQ ID NO: 933)
TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATAATCCAA
AGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC

The sequences of the housekeeping genes measured in all the examples on normal tissue samples panel were as follows:

RPL19 (GenBank Accession No. NM_000981, (SEQ ID NO: 934))
RPL19 Forward primer: (SEQ ID NO: 935)
TGGCAAGAAGAAGGTCTGGTTAG
RPL19 reverse primer: (SEQ ID NO: 936)
TGATCAGCCCATCTTTGATGAG
RPL19-amplicon: (SEQ ID NO: 937)
TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCAATGCCA
ACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA
TATA box (GenBank Accession No. NM_003194, (SEQ ID NO: 938))
TATA box Forward primer: (SEQ ID NO: 939)
CGGTTTGCTGCGGTAATCAT
TATA box Reverse primer: (SEQ ID NO: 940)
TTTCTTGCTGCCAGTCTGGAC
TATA box-amplicon: (SEQ ID NO: 941)
CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACTGATTTT
CAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAGTCCAGACTG
GCAGCAAGAAA
UBC (GenBank Accession No. BC000449 (SEQ ID NO: 942))
UBC Forward primer: (SEQ ID NO: 943)
ATTTGGGTCGCGGTTCTTG
UBC reverse primer: (SEQ ID NO: 944)
TGCCTTGACATTCTCGATGGT
UBC-amplicon: (SEQ ID NO: 945)
ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAATGCAGAT
CTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG
TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA
SDHA (GenBank Accession No. NM_004168 (SEQ ID NO: 922))
SDHA Forward primer: (SEQ ID NO: 923)
TGGGAACAAGAGGGCATCTG
SDHA reverse primer: (SEQ ID NO: 924)
CCACCACTGCATCAAATTCATG
SDHA-amplicon: (SEQ ID NO: 925)
TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT
AGTGGATCATGAATTTGATGCAGTGGTGG

Oligonucleotide-Based Micro-Array Experiment Protocol—

Microarray Fabrication

Microarrays (chips) were printed by pin deposition using the MicroGrid II MGII 600 robot from BioRobotics Limited (Cambridge, UK). 50-mer oligonucleotides target sequences were designed by Compugen Ltd (Tel-Aviv, IL) as described by A. Shoshan et al, “Optical technologies and informatics”, Proceedings of SPIE. Vol 4266, pp. 86-95 (2001). The designed oligonucleotides were synthesized and purified by desalting with the Sigma-Genosys system (The Woodlands, Tex., US) and all of the oligonucleotides were joined to a C6 amino-modified linker at the 5â€Č end, or being attached directly to CodeLink slides (Cat #25-6700-01. Amersham Bioscience, Piscataway, N.J., US). The 50-mer oligonucleotides, forming the target sequences, were first suspended in Ultra-pure DDW (Cat # 01-866-1A Kibbutz Beit-Haemek, Israel) to a concentration of 50 ÎŒM. Before printing the slides, the oligonucleotides were resuspended in 300 mM sodium phosphate (pH 8.5) to final concentration of 150 mM and printed at 35-40% relative humidity at 21° C.

Each slide contained a total of 9792 features in 32 subarrays. Of these features, 4224 features were sequences of interest according to the present invention and negative controls that were printed in duplicate. An additional 288 features (96 target sequences printed in triplicate) contained housekeeping genes from Human Evaluation Library2, Compugen Ltd, Israel. Another 384 features are E.coli spikes 1-6, which are oligos to E-Coli genes which are commercially available in the Array Control product (Array control-sense oligo spots, Ambion Inc. Austin, Tex. Cat # 1781, Lot # 112K06).

Post-Coupling Processing of Printed Slides

After the spotting of the oligonucleotides to the glass (CodeLink) slides, the slides were incubated for 24 hours in a sealed saturated NaCl humidification chamber (relative humidity 70-75%).

Slides were treated for blocking of the residual reactive groups by incubating them in blocking solution at 50° C for 15 minutes (10 ml/slide of buffer containing 0.1M Tris, 50 mM ethanolamine, 0.1% SDS). The slides were then rinsed twice with Ultra-pure DDW (double distilled water). The slides were then washed with wash solution (10 ml/slide. 4×SSC, 0.1% SDS)) at 50° C. for 30 minutes on the shaker. The slides were then rinsed twice with Ultra-pure DDW, followed by drying by centrifugation for 3 minutes at 800 rpm.

Next, in order to assist in automatic operation of the hybridization protocol, the slides were treated with Ventana Discovery hybridization station barcode adhesives. The printed slides were loaded on a Bio-Optica (Milan, Italy) hematology staining device and were incubated for 10 minutes in 50 ml of 3-Aminopropyl Triethoxysilane (Sigma A3648 lot #122K589). Excess fluid was dried and slides were then incubated for three hours in 20 mm/Hg in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding Calif.).

The following protocol was then followed with the Genisphere 900-RP (random primer), with mini elute columns on the Ventana Discovery HybStationℱ, to perform the microarray experiments. Briefly, the protocol was performed as described with regard to the instructions and information provided with the device itself. The protocol included cDNA synthesis and labeling. cDNA concentration was measured with the TBS-380 (Turner Biosystems. Sunnyvale, Calif.) PicoFlour, which is used with the OliGreen ssDNA Quantitation reagent and kit. Hybridization was performed with the Ventana Hybridization device, according to the provided protocols (Discovery Hybridization Station Tuscon Ariz.).

The slides were then scanned with GenePix 4000B dual laser scanner from Axon Instruments Inc, and analyzed by GenePix Pro 5.0 software.

Schematic summary of the oligonucleotide based microarray fabrication and the experimental flow is presented in FIGS. 4 and 5.

Briefly, as shown in FIG. 4, DNA oligonucleotides at 25 uM were deposited (printed) onto Amersham ‘CodeLink’ glass slides generating a well defined ‘spot’. These slides are covered with a long-chain, hydrophilic polymer chemistry that creates an active 3-D surface that covalently binds the DNA oligonucleotides 5â€Č-end via the C6-amine modification. This binding ensures that the full length of the DNA oligonucleotides is available for hybridization to the cDNA and also allows lower background, high sensitivity and reproducibility.

FIG. 5 shows a schematic method for performing the microarray experiments. It should be noted that stages on the left-hand or right-hand side may optionally be performed in any order, including in parallel, until stage 4 (hybridization). Briefly, on the left-hand side, the target oligonucleotides are being spotted on a glass microscope slide (although optionally other materials could be used) to form a spotted slide (stage 1). On the right hand side, control sample RNA and cancer sample RNA are Cy3 and Cy5 labeled, respectively (stage 2), to form labeled probes. It should be noted that the control and cancer samples come from corresponding tissues (for example, normal prostate tissue and cancerous prostate tissue). Furthermore, the tissue from which the RNA was taken is indicated below in the specific examples of data for particular clusters, with regard to overexpression of an oligonucleotide from a “chip” (microarray), as for example “prostate” for chips in which prostate cancerous tissue and normal tissue were tested as described above. In stage 3, the probes are mixed. In stage 4, hybridization is performed to form a processed slide. In stage 5, the slide is washed and scanned to form an image file, followed by data analysis in stage 6.

Description for Cluster T10888

Cluster T10888 features 4 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
T10888_PEA_1_T1 1
T10888_PEA_1_T4 2
T10888_PEA_1_T5 3
T10888_PEA_1_T6 4

TABLE 2
Segments of interest
Segment Name Sequence ID No.
T10888_PEA_1_node_11 5
T10888_PEA_1_node_12 6
T10888_PEA_1_node_17 7
T10888_PEA_1_node_4 8
T10888_PEA_1_node_6 9
T10888_PEA_1_node_7 10
T10888_PEA_1_node_9 11
T10888_PEA_1_node_15 12

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
T10888_PEA_1_P2 14
T10888_PEA_1_P4 15
T10888_PEA_1_P5 16
T10888_PEA_1_P6 17

These sequences are variants of the known protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) (SwissProt accession identifier CEA6_HUMAN; known also according to the synonyms Normal cross-reacting antigen; Nonspecific crossreacting antigen; CD66c antigen), SEQ ID NO:13, referred to herein as the previously known protein.

The sequence for protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) is given at the end of the application, as “Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
138 F -> L
239 V -> G

Protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) localization is believed to be Attached to the membrane by a GPI-anchor.

The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Immunostimulant. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Imaging agent; Anticancer; Immunostimulant; Immunoconjugate; Monoclonal antibody, murine; Antisense therapy; antibody.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: signal transduction; cell-cell signaling, which are annotation(s) related to Biological Process; and integral plasma membrane protein, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster T10888 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of FIG. 6 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 6 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma.

TABLE 5
Normal tissue distribution
Name of Tissue Number
Bladder 0
Colon 107
Epithelial 52
General 22
head and neck 40
Lung 237
Breast 0
pancreas 32
Prostate 12
Stomach 0

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
Bladder 5.4e−01 3.4e−01 5.6e−01 1.8 4.6e−01 1.9
Colon 1.2e−01 1.7e−01 2.8e−05 3.7 7.9e−04 2.8
epithelial 3.3e−02 2.1e−01 2.8e−20 2.8 4.8e−10 1.9
General 3.3e−05 2.2e−03 1.9e−44 4.9 4.6e−27 3.3
head and neck 4.6e−01 4.3e−01 1 0.8 7.5e−01 1.0
Lung 7.6e−01 8.2e−01 8.9e−01 0.6 1 0.3
Breast 3.7e−02 4.1e−02 1.5e−01 3.3 3.1e−01 2.4
pancreas 2.6e−01 2.4e−01 8.6e−23 2.8 1.5e−19 4.5
Prostate 9.1e−01 9.3e−01 4.1e−02 1.2 1.0e−01 1.0
Stomach 4.5e−02 5.6e−02 5.1e−04 4.1 4.7e−04 6.3

As noted above, cluster T10888 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13). A description of each variant protein according to the present invention is now provided.

Variant protein T10888_PEA—1_P2 (SEQ ID NO:14) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA—1_T1 (SEQ ID NO:1). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T10888_PEA—1_P2 (SEQ ID NO:14) and CEA6_HUMAN (SEQ ID NO:13):

1. An isolated chimeric polypeptide encoding for T10888_PEA—1_P2 (SEQ ID NO:14), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1-319 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-319 of T10888_PEA—1_P2 (SEQ ID NO:14), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP (SEQ ID NO:999) corresponding to amino acids 320-324 of T10888_PEA—1_P2 (SEQ ID NO:14), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA—1_P2 (SEQ ID NO:14), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP (SEQ ID NO:999) in T10888_PEA—1_P2 (SEQ ID NO:14).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T10888_PEA—1_P2 (SEQ ID NO:14) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P2 (SEQ ID NO:14) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
13 V -> No
232 N -> D No
324 P -> No
63 I -> No
92 G -> No

Variant protein T10888_PEA—1_P2 (SEQ ID NO:14) is encoded by the following transcript(s): T10888_PEA—1_T1 (SEQ ID NO:1), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA—1_T1 (SEQ ID NO:1) is shown in bold; this coding portion starts at position 151 and ends at position 1122. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1—P2 (SEQ ID NO:14) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
119 C -> T No
120 A -> T No
1062 A -> G Yes
1120 C -> No
1297 G -> T Yes
1501 A -> G Yes
1824 G -> A No
2036 A -> C No
2036 A -> G No
2095 A -> C No
2242 A -> C No
2245 A -> C No
189 C -> No
2250 A -> T Yes
2339 C -> A Yes
276 G -> A Yes
338 T -> No
424 G -> No
546 A -> G No
702 C -> T No
844 A -> G No
930 C -> T Yes

Variant protein T10888_PEA—1_P4 (SEQ ID NO:15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA—1_T4 (SEQ ID NO:2). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T10888_PEA—1_P4 (SEQ ID NO:15) and CEA6_HUMAN SEQ ID NO:13):

1. An isolated chimeric polypeptide encoding for T10888_PEA—1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to

MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP
QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG
FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL
WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL

corresponding to amino acids 1-234 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-234 of T10888_PEA—1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) corresponding to amino acids 235-256 of T10888_PEA—1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA—1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) in T10888_PEA—1_P4 (SEQ ID NO:15).

Comparison report between T10888_PEA—1_P4 (SEQ ID NO:15) and Q13774 (SEQ ID NO:829):

1. An isolated chimeric polypeptide encoding for T10888_PEA—1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of Q13774, which also corresponds to amino acids 1-234 of T10888_PEA—1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) corresponding to amino acids 235-256 of T10888_PEA—1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA—1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) in T10888_PEA—1_P4 (SEQ ID NO:15).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T10888_PEA—1_P4 (SEQ ID NO:15 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P4 (SEQ ID NO:15) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
13 V -> No
232 N -> D No
63 I -> No
92 G -> No

Variant protein T10888_PEA—1_P4 (SEQ ID NO:15) is encoded by the following transcript(s): T10888_PEA—1_T4 (SEQ ID NO:2), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA—1_T4 (SEQ ID NO:2) is shown in bold; this coding portion starts at position 151 and ends at position 918. The transcript also the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P4 SEQ ID NO:15) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
119 C -> T No
120 A -> T No
978 C -> No
1155 G -> T Yes
1359 A -> G Yes
1682 G -> A No
1894 A -> C No
1894 A -> G No
1953 A -> C No
2100 A -> C No
2103 A -> C No
2108 A -> T Yes
189 C -> No
2197 C -> A Yes
276 G -> A Yes
338 T -> No
424 G -> No
546 A -> G No
702 C -> T No
844 A -> G No
958 G -> No

Variant protein T10888_PEA—1_P5 (SEQ ID NO:16) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA—1_T5 (SEQ ID NO:3). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T10888_PEA—1_P5 (SEQ ID NO:16) and CEA6_HUMAN (SEQ ID NO:13):

1. An isolated chimeric polypeptide encoding for T10888_PEA—1_P5 (SEQ ID NO:16), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1-320 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-320 of T10888_PEA—1_P5 (SEQ ID NO:16), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV (SEQ ID NO:1001) corresponding to amino acids 321-390 of T10888_PEA—1_P5 (SEQ ID NO:16), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA—1_P5 (SEQ ID NO:16), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF (SEQ ID NO: 1001)
VVFCFLISHV
in T10888_PEA_1_P5. (SEQ ID NO: 16)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

Variant protein T10888_PEA—1_P5 (SEQ ID NO:16) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P5 (SEQ ID NO:16) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
13 V -> No
232 N -> D No
63 I -> No
92 G -> No

Variant protein T10888_PEA—1_P5 (SEQ ID NO 16) is encoded by the following transcript(s): T10888_PEA—1_T5 (SEQ ID NO:3), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA—1_T5 (SEQ ID NO:3) is shown in bold; this coding portion starts at position 151 and ends at position 1320. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P5 (SEQ ID NO:16) sequence provides support for the deduced sequence of variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
119 C -> T No
120 A -> T No
1062 A -> G Yes
1943 C -> A Yes
2609 C -> T Yes
2647 C -> G No
2701 C -> T Yes
2841 T -> C Yes
189 C -> No
276 G -> A Yes
338 T -> No
424 G -> No
546 A -> G No
702 C -> T No
844 A -> G No
930 C -> T Yes

Variant protein T10888_PEA—1_P6 (SEQ ID NO:17) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA—1_T6 (SEQ ID NO:4). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application.

Comparison report between T10888_PEA—1_P6 (SEQ ID NO:17) and CEA6_HUMAN (SEQ ID NO:13):

1. An isolated chimeric polypeptide encoding for T10888_PEA—1_P6 (SEQ ID NO:17), comprising a first amino acid sequence being at least 90% homologous to

    MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLA
HNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQ
NDTGFYTLQVIKSDLVNEEATGQFHVY

corresponding to amino acids 1-141 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-141 of T10888_PEA—1_P6 (SEQ ID NO:17), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

(SEQ ID NO: 1002)
REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI

corresponding to amino acids 142-183 of T10888_PEA—1_P6 (SEQ ID NO:17), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA—1_P6 (SEQ ID NO:17), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO: 1002)
REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI
(SEQ ID NO: 17)
in T10888_PEA_1_P6.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T10888_PEA—1_P6 (SEQ ID NO:17) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P6 (SEQ ID NO:17) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
13 V -> No
63 I -> No
92 G -> No

Variant protein T10888_PEA—1_P6 (SEQ ID NO:17) is encoded by the following transcript(s): T10888_PEA—1_T6 (SEQ ID NO:4), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA—1_T6 (SEQ ID NO:4) is shown in bold; this coding portion starts at position 151 and ends at position 699. The transcript also as the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA—1_P6 (SEQ ID NO:17) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
119 C -> T No
120 A -> T No
189 C -> No
276 G -> A Yes
338 T -> No
424 G -> No
546 A -> G No

As noted above, cluster T10888 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T10888_PEA—1_node—11 (SEQ ID NO:5) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T1 (SEQ ID NO:1) and T10888_PEA—1_T5 (SEQ ID NO:3). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T1 (SEQ ID 854 1108
NO: 1)
T10888_PEA_1_T5 (SEQ ID 854 1108
NO: 3)

Segment cluster T10888_PEA—1_node—12 (SEQ ID NO:6) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T5 (SEQ ID NO:3). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T5 (SEQ ID 1109 3004
NO: 3)

Segment cluster T10888_PEA—1_node—17 (SEQ ID NO:7) according to the present invention is supported by 160 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T1 (SEQ ID NO:1) and T10888_PEA—1_T4 (SEQ ID NO:2). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T1 (SEQ ID 1109 2518
NO: 1)
T10888_PEA_1_T4 (SEQ ID 967 2376
NO: 2)

Segment cluster T10888_PEA—1_node—4 (SEQ ID NO:8) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T1 (SEQ ID NO:1), T10888_PEA—1_T4 (SEQ ID NO:2), T10888_PEA—1_T5 (SEQ ID NO:3) and T10888_PEA—1_T6 (SEQ ID NO:4). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T1 (SEQ ID 1 214
NO: 1)
T10888_PEA_1_T4 (SEQ ID 1 214
NO: 2)
T10888_PEA_1_T5 (SEQ ID 1 214
NO: 3)
T10888_PEA_1_T6 (SEQ ID 1 214
NO: 4)

Segment cluster T10888_PEA—1_node—6 (SEQ ID NO:9) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T1 (SEQ ID NO:1), T10888_PEA—1_T4 (SEQ ID NO:2), T10888_PEA—1_T5 (SEQ ID NO:3) and T10888_PEA—1_T6 (SEQ ID NO:4). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T1 (SEQ ID 215 574
NO: 1)
T10888_PEA_1_T4 (SEQ ID 215 574
NO: 2)
T10888_PEA_1_T5 (SEQ ID 215 574
NO: 3)
T10888_PEA_1_T6 (SEQ ID 215 574
NO: 4)

Segment cluster T10888_PEA—1_node—7 (SEQ ID NO:10) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T6 (SEQ ID NO:4). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T6 (SEQ ID 575 1410
NO: 4)

Segment cluster T10888_PEA—1_node—9 (SEQ ID NO:11) according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T1 (SEQ ID NO:1), T10888_PEA—1_T4 (SEQ ID NO:2) and T10888_PEA—1_T5 (SEQ ID NO:3). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T1 (SEQ ID 575 853
NO: 1)
T10888_PEA_1_T4 (SEQ ID 575 853
NO: 2)
T10888_PEA_1_T5 (SEQ ID 575 853
NO: 3)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster T10888_PEA—1_node—15 (SEQ ID NO:12) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA—1_T4 (SEQ ID NO:2). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T10888_PEA_1_T4 (SEQ ID 854 966
NO: 2)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/tM4EgaoKvm/vuztUrlRc7:CEA6_HUMAN (SEQ ID NO:13).

Sequence documentation:

Alignment of: T10888_PEA—1_P2 (SEQ ID NO:14)×CEA6_HUMAN (SEQ ID NO:13)

Alignment segment 1/1:

Quality: 3163.00
Escore: 0
Matching length: 319 Total length: 319
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
         .         .         .         .         .
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
         .         .         .         .         .
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
         .         .         .         .         .
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
         .         .         .         .         .
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250
         .         .         .         .         .
251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300
         .
301 AHNSATGLNRTTVTMITVS 319
|||||||||||||||||||
301 AHNSATGLNRTTVTMITVS 319

Sequence name: /tmp/Yjl1gj7TCe/PgdufzLOlW:CEA6_HUMAN (SEQ ID NO:13)

Sequence documentation:

Alignment of: T10888_PEA—1_P4 (SEQ ID NO:15)×CEA6_HUMAN (SEQ ID NO:13).

Alignment segment 1/1:

Quality: 2310.00
Escore: 0
Matching length: 234 Total length: 234
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
         .         .         .         .         .
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
         .         .         .         .         .
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATCQFHVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
         .         .         .         .         .
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
         .         .         .
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234
||||||||||||||||||||||||||||||||||
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234

Sequence name: /tmp/Yjl1gj7TCe/PgdufzLOlW:Q13774

Sequence documentation:

Alignment of: T10888_PEA—1_P4 (SEQ ID NO:15)×Q13774.

Alignment segment 1/1:

Quality: 2310.00
Escore: 0
Matching length: 234 Total length: 234
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
         .         .         .         .         .
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
         .         .         .         .         .
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
         .         .         .         .         .
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
         .         .         .
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234
||||||||||||||||||||||||||||||||||
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234

Sequence name: /tmp/x5xDBacdpj/rTXRGepv3y:CEA6_HUMAN (SEQ ID NO:13)

Sequence documentation:

Alignment of: T10888_PEA—1_P5 (SEQ ID NO:16)×CEA6_HUMAN (SEQ ID NO:13).

Alignment segment 1/1:

Quality: 3172.00
Escore: 0
Matching length: 320 Total length: 320
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
         .         .         .         .         .
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
         .         .         .         .         .
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150
         .         .         .         .         .
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200
         .         .         .         .         .
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250
         .         .         .         .         .
251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300
         .         .
301 AHNSATGLNRTTVTMITVSG 320
||||||||||||||||||||
301 AHNSATGLNRTTVTMITVSG 320

Sequence name: /tmp/VAhvYFeatq/QNEM573uCo:CEA6_HUMAN (SEQ ID NO:13)

Sequence documentation:

Alignment of: T10888_PEA—1_P6 (SEQ ID NO:17)×CEA6_HUMAN (SEQ ID NO:13).

Alignment segment 1/1:

Quality: 1393.00
Escore: 0
Matching length: 143 Total length: 143
Matching Percent 99.30 Matching Percent Identity: 99.30
Similarity:
Total Percent Similarity: 99.30 Total Percent Identity: 99.30
Gaps: 0

Alignment:

         .         .         .         .         .
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
         .         .         .         .         .
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
         .         .         .         .
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYRE 143
||||||||||||||||||||||||||||||||||||||||| |
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPE 143

Alignment of: T10888_PEA—1_P6 (SEQ ID NO:17)×CEA6_HUMAN (SEQ ID NO:13).

Alignment segment 1/1:

Quality: 101.00
Escore: 0
Matching length: 141 Total length: 183
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 77.05 Total Percent Identity: 77.05
Gaps: 1

Alignment:

         .         .         .         .         .
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50
         .         .         .         .         .
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100
         .         .         .         .         .
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYREYFHMTSG 150
|||||||||||||||||||||||||||||||||||||||||
101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVY......... 141
         .         .         .
151 CWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI 183
141 ................................. 141

Expression of CEA6_HUMAN Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 (T10888) Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T10888 junc11-17 in Normal and Cancerous Breast Tissues

Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to junc11-17, T10888junc11-17 (SEQ ID NO:832) amplicon(s) and T10888junc11-17F (SEQ ID NO:830) and T10888junc11-17R primers was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922Q; amplicon—SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67 Table 1, “Tissue samples in testing panel”, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 7 is a histogram showing over expression of the above-indicated CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested, is indicated in the bottom.

As is evident from FIG. 7, the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 19 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 2.00E-03.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 8.44E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T10888junc11-17F (SEQ ID NO:830) forward primer; and T10888junc11-17R reverse primer.

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T10888junc11-17.

T10888junc11-17F (SEQ ID NO: 830)
CCAGCAATCCACACAAGAGCT
T10888junc11-17R (SEQ ID NO: 831)
CAGGGTCTGGTCCAATCAGAG
T10888junc11-17 (SEQ ID NO: 832)
    CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATAGC
GGATCCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGGACCACAGT
CACGATGATCACAGTCTCTGATTGGACCAGACCCTG

Expression of CEA6_HUMAN Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6T10888 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T10888junc11-17 (SEQ ID NO:832) in Different Normal Tissues

Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to T10888 junc11-17 amplicon(s) (SEQ ID NO:832) and T10888 junc11-17F (SEQ ID NO:830) and T10888 junc11-17R (SEQ ID NO:831) was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945 ) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2 “Tissue samples in normal panel” above), to obtain a value of relative expression of each sample relative to median of the ovary samples. Primers and amplicon are as above.

The results are presented in FIG. 8, demonstrating the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 T10888 transcripts, which are detectable by amplicon as depicted in sequence name T10888junc11-17 (SEQ ID NO:832), in different normal tissues.

Description for Cluster T39971

Cluster T39971 features 4 transcript(s) and 28 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
T39971_T10 18
T39971_T12 19
T39971_T16 20
T39971_T5 21

TABLE 2
Segments of interest
Segment Name Sequence ID No.
T39971_node_0 22
T39971_node_18 23
T39971_node_21 24
T39971_node_22 25
T39971_node_23 26
T39971_node_31 27
T39971_node_33 28
T39971_node_7 29
T39971_node_1 30
T39971_node_10 31
T39971_node_11 32
T39971_node_12 33
T39971_node_15 34
T39971_node_16 35
T39971_node_17 36
T39971_node_26 37
T39971_node_27 38
T39971_node_28 39
T39971_node_29 40
T39971_node_3 41
T39971_node_30 42
T39971_node_34 43
T39971_node_35 44
T39971_node_36 45
T39971_node_4 46
T39971_node_5 47
T39971_node_8 48
T39971_node_9 49

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
T39971_P6 51
T39971_P9 52
T39971_P11 53
T39971_P12 54

These sequences are variants of the known protein Vitronectin precursor (SwissProt accession identifier VTNC_HUMAN; known also according to the synonyms Serum spreading factor; S-protein; V75), SEQ ID NO:50, referred to herein as the previously known protein.

Protein Vitronectin precursor (SEQ ID NO:50) is known or believed to have the following function(s): Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interacts with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. The sequence for protein Vitronectin precursor is given at the end of the application, as “Vitronectin precursor amino acid sequence” (SEQ ID NO:50). Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
122 A -> S. /FTId = VAR_012983.
268 R -> Q. /FTId = VAR_012984.
400 T -> M. /FTId = VAR_012985.
50 C -> N
225 S -> N
366 A -> T

Protein Vitronectin precursor (SEQ ID NO:50) localization is believed to be Extracellular.

The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer, melanoma. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Alphavbeta3 integrin antagonist; Apoptosis agonist. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anticancer.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: immune response; cell adhesion, which are annotation(s) related to Biological Process; protein binding; heparin binding, which are annotation(s) related to Molecular Function; and extracellular space, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster T39971 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of FIG. 9 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 9 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: liver cancer, lung malignant tumors and pancreas carcinoma.

TABLE 5
Normal tissue distribution
Name of Tissue Number
adrenal 60
bladder 0
Bone 0
Brain 9
Colon 0
epithelial 79
general 29
Liver 2164
Lung 0
lymph nodes 0
breast 0
pancreas 0
prostate 0
Skin 0
uterus 0

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 6.9e−01 7.4e−01 2.0e−02 2.3 5.3e−02 1.8
bladder 5.4e−01 6.0e−01 5.6e−01 1.8 6.8e−01 1.5
Bone 1 6.7e−01 1 1.0 7.0e−01 1.4
Brain 8.0e−01 8.6e−01 3.0e−01 1.9 5.3e−01 1.2
Colon 4.2e−01 4.8e−01 7.0e−01 1.6 7.7e−01 1.4
epithelial 6.6e−01 5.7e−01 1.0e−01 0.8 8.7e−01 0.6
general 5.1e−01 3.8e−01 9.2e−08 1.6 8.3e−04 1.3
Liver 1 6.7e−01 2.3e−03 0.3 1 0.2
Lung 2.4e−01 9.1e−02 1.7e−01 4.3 8.1e−03 5.0
lymph nodes 1 5.7e−01 1 1.0 5.8e−01 2.3
breast 1 6.7e−01 1 1.0 8.2e−01 1.2
pancreas 9.5e−02 1.8e−01 1.5e−11 6.5 8.2e−09 4.6
prostate 7.3e−01 6.0e−01 6.7e−01 1.5 5.6e−01 1.7
Skin 1 4.4e−01 1 1.0 6.4e−01 1.6
uterus 5.0e−01 2.6e−01 1 1.1 8.0e−01 1.4

As noted above, cluster T39971 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Vitronectin precursor (SEQ ID NO:50). A description of each variant protein according to the present invention is now provided.

Variant protein T39971_P6 (SEQ ID NO:51) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T5 (SEQ ID NO:21). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T39971_P6 (SEQ ID NO:51) and VTNC_HUMAN (SEQ ID NO:50):

1. An isolated chimeric polypeptide encoding for T39971_P6 (SEQ ID NO:51), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids 1-276 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-276 of T39971_P6 (SEQ ID NO:51),and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQGVVGD (SEQ ID NO:1003) corresponding to amino acids 277-283 of T39971_P6 (SEQ ID NO:51), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T39971_P6 (SEQ ID NO:51), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TQGVVGD (SEQ ID NO:1003) in T39971_P6 (SEQ ID NO:51).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T39971_P6 (SEQ ID NO:51) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P6 (SEQ ID NO:51) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
122 A -> S Yes
145 G -> No
268 R -> Q Yes
280 V -> A Yes
180 C -> No
180 C -> W No
192 Y -> No
209 A -> No
211 T -> No
267 G -> No
267 G -> A No
268 R -> No

Variant protein T39971_P6 (SEQ ID NO:51) is encoded by the following transcript(s): T39971_T5 (SEQ ID NO:21), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T5 (SEQ ID NO:21) is shown in bold; this coding portion starts at position 756 and ends at position 1604. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P6 (SEQ ID NO:51) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
417 G -> C Yes
459 T -> C Yes
1387 C -> No
1406 -> A No
1406 -> G No
1555 G -> No
1555 G -> C No
1558 G -> No
1558 G -> A Yes
1594 T -> C Yes
1642 T -> C Yes
1770 C -> T Yes
529 G -> T Yes
1982 A -> G No
2007 G -> No
2029 T -> C No
2094 T -> C No
2117 C -> G No
2123 C -> T Yes
2152 C -> T Yes
2182 G -> T No
2185 A -> C No
2297 T -> C Yes
1119 G -> T Yes
2411 G -> No
2411 G -> T No
2487 T -> C Yes
1188 G -> No
1295 C -> No
1295 C -> G No
1324 -> T No
1331 C -> No
1381 C -> No

Variant protein T39971_P9 (SEQ ID NO:52) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T10 (SEQ ID NO:18). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T39971_P9 (SEQ ID NO:52) and VTNC_HUMAN (SEQ ID NO:50):

1. An isolated chimeric polypeptide encoding for T39971_P9 (SEQ ID NO:52), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids 1-325 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-325 of T39971_P9 (SEQ ID NO:52), and a second amino acid sequence being at least 90% homologous to SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNONSRRPSRATWLSLFSSEESNLGA NNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGC PAPGHL corresponding to amino acids 357-478 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 326-447 of T39971_P9 (SEQ ID NO:52), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T39971_P9 (SEQ ID NO:52), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T39971_P9 (SEQ ID NO:52) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P9 (SEQ ID NO:52) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
122 A -> S Yes
145 G -> No
268 R -> Q Yes
328 M -> T No
350 S -> P No
369 T -> M Yes
379 S -> I No
380 N -> T No
180 C -> No
180 C -> W No
192 Y -> No
209 A -> No
211 T -> No
267 G -> No
267 G -> A No
268 R -> No

Variant protein T39971_P9 (SEQ ID NO:52) is encoded by the following transcript(s): T39971_T10 (SEQ ID NO:18), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T10 (SEQ ID NO:18) is shown in bold; this coding portion starts at position 756 and ends at position 2096. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P9 (SEQ ID NO:52) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
417 G -> C Yes
459 T -> C Yes
1387 C -> No
1406 -> A No
1406 -> G No
1555 G -> No
1555 G -> C No
1558 G -> No
1558 G -> A Yes
1738 T -> C No
1803 T -> C No
1826 C -> G No
529 G -> T Yes
1832 C -> T Yes
1861 C -> T Yes
1891 G -> T No
1894 A -> C No
2006 T -> C Yes
2120 G -> No
2120 G -> T No
2196 T -> C Yes
1119 G -> T Yes
1188 G -> No
1295 C -> No
1295 C -> G No
1324 -> T No
1331 C -> No
1381 C -> No

Variant protein T39971_P11 (SEQ ID NO:53) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T12 (SEQ ID NO:19). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T39971_P11 (SEQ ID NO:53) and VTNC_HUMAN (SEQ ID NO:50):

1. An isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n−2)−x), in which x varies from 0 to n−2.

Comparison report between T39971_P11 (SEQ ID NO:53) and Q9BSH7 (SEQ ID NO:833):

1. An isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of Q9BSH7, which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of Q9BSH7, which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T39971_P11 (SEQ ID NO:53) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P11 (SEQ ID NO:53) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
122 A -> S Yes
145 G -> No
268 R -> Q Yes
180 C -> No
180 C -> W No
192 Y -> No
209 A -> No
211 T -> No
267 G -> No
267 G -> A No
268 R -> No

Variant protein T39971_P11 (SEQ ID NO:53) is encoded by the following transcript(s): T39971_T12 (SEQ ID NO:19), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T12 (SEQ ID NO:19) is shown in bold; this coding portion starts at position 756 and ends at position 1844. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P11 (SEQ ID NO:53) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
417 G -> C Yes
459 T -> C Yes
1387 C -> No
1406 -> A No
1406 -> G No
1555 G -> No
1555 G -> C No
1558 G -> No
1558 G -> A Yes
1754 T -> C Yes
1868 G -> No
1868 G -> T No
529 G -> T Yes
1944 T -> C Yes
1119 G -> T Yes
1188 G -> No
1295 C -> No
1295 C -> G No
1324 -> T No
1331 C -> No
1381 C -> No

Variant protein T39971_P12 (SEQ ID NO:54) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T16 (SEQ ID NO:20). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T39971_P12 (SEQ ID NO:54) and VTNC_HUMAN (SEQ ID NO:50):

1. An isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54).

Comparison report between T39971_P12 (SEQ ID NO:54) and Q9BSH7:

1. An isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of Q9BSH7, which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T39971_P12 (SEQ ID NO:54) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P 12 (SEQ ID NO:54) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
122 A -> S Yes
145 G -> No
180 C -> No
180 C -> W No
192 Y -> No
209 A -> No
211 T -> No

Variant protein T39971_P12 (SEQ ID NO:54) is encoded by the following transcript(s): T39971_T16 (SEQ ID NO:20), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T16 (SEQ ID NO:20) is shown in bold; this coding portion starts at position 756 and ends at position 1469. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P12 (SEQ ID NO:54) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
417 G -> C Yes
459 T -> C Yes
1387 C -> No
1406 -> A No
1406 -> G No
529 G -> T Yes
1119 G -> T Yes
1188 G -> No
1295 C -> No
1295 C -> G No
1324 -> T No
1331 C -> No
1381 C -> No

As noted above, cluster T39971 features 28 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T39971_node—0 (SEQ ID NO:22) according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T1 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1 810
T39971_T12 (SEQ ID NO: 19) 1 810
T39971_T16 (SEQ ID NO: 20) 1 810
T39971_T5 (SEQ ID NO: 21) 1 810

Segment cluster T39971_node—18 (SEQ ID NO:23) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T16 (SEQ ID NO:20). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T16 (SEQ ID NO: 20) 1425 1592

Segment cluster T39971_node—21 (SEQ ID NO:24) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1425 1581
T39971_T12 (SEQ ID NO: 19) 1425 1581
T39971_T5 (SEQ ID NO: 21) 1425 1581

Segment cluster T39971_node—22 (SEQ ID NO:25) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5 (SEQ ID NO:21). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T5 (SEQ ID NO: 21) 1582 1779

Segment cluster T39971_node—23 (SEQ ID NO:26) according to the present invention is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1582 1734
T39971_T12 (SEQ ID NO: 19) 1582 1734
T39971_T5 (SEQ ID NO: 21) 1780 1932

Segment cluster T39971_node—31 (SEQ ID NO:27) according to the present invention is supported by 94 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18) and T39971_T5 (SEQ ID NO:21). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1847 1986
T39971_T5 (SEQ ID NO: 21) 2138 2277

Segment cluster T39971_node—33 (SEQ ID NO:28) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1987 2113
T39971_T12 (SEQ ID NO: 19) 1735 1861
T39971_T5 (SEQ ID NO: 21) 2278 2404

Segment cluster T39971_node—7 (SEQ ID NO:29) according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T11 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 940 1162
T39971_T12 (SEQ ID NO: 19) 940 1162
T39971_T16 (SEQ ID NO: 20) 940 1162
T39971_T5 (SEQ ID NO: 21) 940 1162

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster T39971_node—1 (SEQ ID NO:30) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 811 819
T39971_T12 (SEQ ID NO: 19) 811 819
T39971_T16 (SEQ ID NO: 20) 811 819
T39971_T5 (SEQ ID NO: 21) 811 819

Segment cluster T39971_node—10 (SEQ ID NO:31) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1189 1232
T39971_T12 (SEQ ID NO: 19) 1189 1232
T39971_T16 (SEQ ID NO: 20) 1189 1232
T39971_T5 (SEQ ID NO: 21) 1189 1232

Segment cluster T39971_node—11 (SEQ ID NO:32) according to the present invention is supported by 79 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1233 1270
T39971_T12 (SEQ ID NO: 19) 1233 1270
T39971_T16 (SEQ ID NO: 20) 1233 1270
T39971_T5 (SEQ ID NO: 21) 1233 1270

Segment cluster T39971_node—12 (SEQ ID NO:33) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1271 1284
T39971_T12 (SEQ ID NO: 19) 1271 1284
T39971_T16 (SEQ ID NO: 20) 1271 1284
T39971_T5 (SEQ ID NO: 21) 1271 1284

Segment cluster T39971_node—15 (SEQ ID NO:34) according to the present invention is supported by 79 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1285 1316
T39971_T12 (SEQ ID NO: 19) 1285 1316
T39971_T16 (SEQ ID NO: 20) 1285 1316
T39971_T5 (SEQ ID NO: 21) 1285 1316

Segment cluster T39971_node—16 (SEQ ID NO:35) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1317 1340
T39971_T12 (SEQ ID NO: 19) 1317 1340
T39971_T16 (SEQ ID NO: 20) 1317 1340
T39971_T5 (SEQ ID NO: 21) 1317 1340

Segment cluster T39971_node—17 (SEQ ID NO:36) according to the present invention is supported by 86 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1341 1424
T39971_T12 (SEQ ID NO: 19) 1341 1424
T39971_T16 (SEQ ID NO: 20) 1341 1424
T39971_T5 (SEQ ID NO: 21) 1341 1424

Segment cluster T39971_node—26 (SEQ ID NO:37) according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5 (SEQ ID NO:21). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T5 (SEQ ID NO: 21) 1933 1974

Segment cluster T39971_node—27 (SEQ ID NO:38) according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5 (SEQ ID NO:21). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T5 (SEQ ID NO: 21) 1975 2025

Segment cluster T39971_node—28 (SEQ ID NO:39) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18) and T39971_T5 (SEQ ID NO:21). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1735 1743
T39971_T5 (SEQ ID NO: 21) 2026 2034

Segment cluster T39971_node—29 (SEQ ID NO:40) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO 18) and T39971_T5 (SEQ ID NO:21). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1744 1838
T39971_T5 (SEQ ID NO: 21) 2035 2129

Segment cluster T39971_node—3 (SEQ ID NO:41) according to the present invention is supported by 78 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 820 861
T39971_T12 (SEQ ID NO: 19) 820 861
T39971_T16 (SEQ ID NO: 20) 820 861
T39971_T5 (SEQ ID NO: 21) 820 861

Segment cluster T39971_node—30 (SEQ ID NO:42) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18) and T39971_T5 (SEQ ID NO:21). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 1839 1846
T39971_T5 (SEQ ID NO: 21) 2130 2137

Segment cluster T39971_node—34 (SEQ ID NO:43) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 2114 2120
T39971_T12 (SEQ ID NO: 19) 1862 1868
T39971_T5 (SEQ ID NO: 21) 2405 2411

Segment cluster T39971_node—35 (SEQ ID NO:44) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 2121 2137
T39971_T12 (SEQ ID NO: 19) 1869 1885
T39971_T5 (SEQ ID NO: 21) 2412 2428

Segment cluster T39971_node—36 (SEQ ID NO:45) according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 2138 2199
T39971_T12 (SEQ ID NO: 19) 1886 1947
T39971_T5 (SEQ ID NO: 21) 2429 2490

Segment cluster T39971_node—4 (SEQ ID NO:46) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 18) 862 881
T39971_T12 (SEQ ID NO: 19) 862 881
T39971_T16 (SEQ ID NO: 20) 862 881
T39971_T5 (SEQ ID NO: 21) 862 881

Segment cluster T39971_node—5 (SEQ ID NO:47) according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:2 1). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
T39971_T10 (SEQ ID NO: 18) 882 939
T39971_T12 (SEQ ID NO: 19) 882 939
T39971_T16 (SEQ ID NO: 20) 882 939
T39971_T5 (SEQ ID NO: 21) 882 939

Segment cluster T39971_node—8 (SEQ ID NO:48) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
T39971_T10 (SEQ ID NO: 18) 1163 1168
T39971_T12 (SEQ ID NO: 19) 1163 1168
T39971_T16 (SEQ ID NO: 20) 1163 1168
T39971_T5 (SEQ ID NO: 21) 1163 1168

Segment cluster T39971_node—9 (SEQ ID NO:49) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
T39971_T10 (SEQ ID NO: 18) 1169 1188
T39971_T12 (SEQ ID NO: 19) 1169 1188
T39971_T16 (SEQ ID NO: 20) 1169 1188
T39971_T5 (SEQ ID NO: 21) 1169 1188

Variant protein alignment to the previously known protein:

Sequence name: /tmp/xkraCL2OcZ/43L7YcPH7x:VTNC_HUMAN (SEQ ID NO:50)

Sequence documentation:

Alignment of: T39971_P6 (SEQ ID NO:51)×VTNC_HUMAN (SEQ ID NO:50).

Alignment segment 1/1:

Quality: 2774.00
Escore: 0
Matching length: 278 Total length: 278
Matching Percent 99.64 Matching Percent Identity: 99.64
Similarity:
Total Percent Similarity: 99.64 Total Percent Identity: 99.64
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
         .         .         .         .         .
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
         .         .         .         .         .
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
         .         .         .         .         .
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
         .         .         .         .         .
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
         .         .
251 PDNVDAALALPAHSYSGRERVYFFKGTQ 278
|||||||||||||||||||||||||| |
251 PDNVDAALALPAHSYSGRERVYFFKGKQ 278

Sequence name: /tmp/X4DeeuSlB4/yMubSR5FPs:VTNC_HUMAN (SEQ ID NO:50)

Sequence documentation:

Alignment of: T39971_P9 (SEQ ID NO:52)×VTNC_HUMAN (SEQ ID NO:50).

Alignment segment 1/1:

Quality: 4430.00
Escore: 0
Matching length: 447 Total length: 478
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 93.51 Total Percent Identity: 93.51
Gaps: 1

Alignment:

         .         .         .         .         .
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
         .         .         .         .         .
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
         .         .         .         .         .
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
         .         .         .         .         .
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
         .         .         .         .         .
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
         .         .         .         .         .
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
         .         .         .         .         .
301 VFEHFAMMQRDSWEDIFELLFWGRT......................... 325
|||||||||||||||||||||||||
301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350
         .         .         .         .         .
326 ......SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 369
      ||||||||||||||||||||||||||||||||||||||||||||
351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400
         .         .         .         .         .
370 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 419
||||||||||||||||||||||||||||||||||||||||||||||||||
401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450
         .         .
420 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 447
||||||||||||||||||||||||||||
451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478

Sequence name: /tmp/jvp1VtnxNy/wxNSeFVZZw:VTNC_HUMAN (SEQ ID NO:50)

Sequence documentation:

Alignment of: T39971_P11 (SEQ ID NO:53)×VTNC_HUMAN (SEQ ID NO:50).

Alignment segment 1/1:

Quality: 3576.00
Escore: 0
Matching length: 363 Total length: 478
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 75.94 Total Percent Identity: 75.94
Gaps: 1

Alignment:

         .         .         .         .         .
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
         .         .         .         .         .
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
         .         .         .         .         .
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
         .         .         .         .         .
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
         .         .         .         .         .
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRTNCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
         .         .         .         .         .
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
         .         .         .         .         .
301 VFEHFAMMQRDSWEDIFELLFWGRTS........................ 326
||||||||||||||||||||||||||
301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350
         .         .         .         .         .
326 .................................................. 326
351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400
         .         .         .         .         .
327 .........................................DKYYRVNLR 335
                                         |||||||||
401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450
         .         .
336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363
||||||||||||||||||||||||||||
451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478

Sequence name: /tmp/jvp1VtnxNy/wxNSeFVZZw:Q9BSH7

Sequence documentation:

Alignment of: T39971_P11 (SEQ ID NO:53)×Q9BSH7

Alignment segment 1/1:

Quality: 3576.00
Escore: 0
Matching length: 363 Total length: 478
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 75.94 Total Percent Identity: 75.94
Gaps: 1

Alignment:

         .         .         .         .         .
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
         .         .         .         .         .
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
         .         .         .         .         .
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
         .         .         .         .         .
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
         .         .         .         .         .
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250
         .         .         .         .         .
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300
         .         .         .         .         .
301 VFEHFAMMQRDSWEDIFELLFWGRTS........................ 326
||||||||||||||||||||||||||
301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350
         .         .         .         .         .
326 .................................................. 326
351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAM 400
         .         .         .         .         .
327 .........................................DKYYRVNLR 335
                                         |||||||||
401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450
         .         .
336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363
||||||||||||||||||||||||||||
451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478

Sequence name: /tmp/fgebv7ir4i/48bTBMziJ0:VTNC_HUMAN (SEQ ID NO:50)

Sequence documentation:

Alignment of: T39971_P12 (SEQ ID NO:54)×VTNC_HUMAN (SEQ ID NO:50).

Alignment segment 1/1:

Quality: 2237.00
Escore: 0
Matching length: 223 Total length: 223
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
         .         .         .         .         .
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
         .         .         .         .         .
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
         .         .         .         .         .
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
         .         .
201 GIEGPIDAAFTRINCQGKTYLFK 223
|||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFK 223

Sequence name: /tmp/fgebv7ir4i/48bTBMziJ0:Q9BSH7

Sequence documentation:

Alignment of: T39971_P12 (SEQ ID NO:54)×Q9BSH7

Alignment segment 1/1:

Quality: 2237.00
Escore: 0
Matching length: 223 Total length: 223
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50
         .         .         .         .         .
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100
         .         .         .         .         .
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150
         .         .         .         .         .
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200
         .         .
201 GIEGPIDAAFTRINCQGKTYLFK 223
|||||||||||||||||||||||
201 GIEGPIDAAFTRINCQGKTYLFK 223

Expression of VTNC_HUMAN Vitronectin (Serum Spreading Factor, Somatomedin B, Complement S-Protein) T39971 Transcripts, Which are Detectable by Amplicon as Depicted in Sequence Name T39971 junc23-33 (SEQ ID NO:836) in Normal and Cancerous Breast Tissues

Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by or according to junc23-33, T39971 junc23-33 amplicon (SEQ ID NO:836) and T39971 junc23-33F (SEQ ID NO:834) and T39971 junc23-33R (SEQ ID NO:835) primers was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold differetial expression for each sample relative to median of the normal PM samples.

FIG. 10 is a histogram showing down regulation of the above-indicated VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 10, the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by the above amplicon in cancer samples was significantly lower than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, “Tissue samples in testing panel”).

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T39971 junc23-33F (SEQ ID NO:834) forward primer; and T39971 junc23-33R (SEQ ID NO:835) reverse primer.

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T39971 junc23-33 (SEQ ID NO:836).

T39971junc22-33F (SEQ ID NO: 834):
GGGGCAGAACCTCTGACAAG
T39971junc22-33R (SEQ ID NO: 835):
GGGCAGCCCAGCCAGTA
T39971junc22-33 amplicon (SEQ ID NO: 836):
GGGGCAGAACCTCTGACAAGTACTACCGAGTCAATCTTCGCACACGGCGAGTGGAC
ACTGTGGACCCTCCCTACCCACGCTCCATCGCTCAGTACTGGCTGGGCTGCCC

Expression of VTNC_HUMAN Vitronectin (Serum Spreading Factor, Somatomedin B, Complement S-Protein), Antisense to SARM1 (T23434), T39971 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T39971junc23-33 (SEQ ID NO:836) in Different Normal Tissues

Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), transcripts detectable by or according to T39971junc23-33 amplicon (SEQ ID NO:836) and T39971junc23-33F (SEQ ID NO:834) and T39971junc23-33R (SEQ ID NO:835) was measured by real time PCR. In parallel the expression of four housekeeping genes-RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos. 33-35, Table 2, “Tissue samples in normal panel” above), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above.

The results are presented in FIG. 11, demonstrating the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), antisense to SARM1 (T23434), T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971junc23-33 (SEQ ID NO:836), in different normal tissues.

Expression of VTNC_HUMAN Vitronectin (Serum Spreading Factor, Somatomedin B, Complement S-Protein) T39971 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T39971 Seg22 (SEQ ID NO:839) in Normal and Cancerous Breast Tissues

Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by or according to seg22, T39971 seg22 (SEQ ID NO:839) amplicon(s) and primers T39971 seg22F (SEQ ID NO:837) and T39971 seg22R (SEQ ID NO:838) was measured by real time PCR. In parallel the expression of four housekeeping genes-PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)); G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a problem that is specific to this particular experiment.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T39971 seg22F (SEQ ID NO:837) forward primer; and T39971 seg22R (SEQ ID NO:838) reverse primer.

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T39971 seg22 (SEQ ID NO:839).

Forward primer T39971 seg22F: (SEQ ID NO: 837)
GCAGTCTTGGATTCCTTTCACATT
Reverse primer T39971 seg22R: (SEQ ID NO: 838)
GAGGCTGTTGAAGTTAGGATCTCC
Amplicon T39971 seg22: (SEQ ID NO: 839)
GCAGTCTTGGATTCCTTTCACATTTCACTGGGGACAGGCCTCAGCATGTGCCCACCC
CTGACCCCCACCTCATGCTGGGAGATCCTAACTTCAACAGCCTC

Description for Cluster Z21368

Cluster Z21368 features 7 transcript(s) and 34 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
Z21368_PEA_1_T10 55
Z21368_PEA_1_T11 56
Z21368_PEA_1_T23 57
Z21368_PEA_1_T24 58
Z21368_PEA_1_T5 59
Z21368_PEA_1_T6 60
Z21368_PEA_1_T9 61

TABLE 2
Segments of interest
Segment Name Sequence ID No.
Z21368_PEA_1_node_0 62
Z21368_PEA_1_node_15 63
Z21368_PEA_1_node_19 64
Z21368_PEA_1_node_2 65
Z21368_PEA_1_node_21 66
Z21368_PEA_1_node_33 67
Z21368_PEA_1_node_36 68
Z21368_PEA_1_node_37 69
Z21368_PEA_1_node_39 70
Z21368_PEA_1_node_4 71
Z21368_PEA_1_node_41 72
Z21368_PEA_1_node_43 73
Z21368_PEA_1_node_45 74
Z21368_PEA_1_node_53 75
Z21368_PEA_1_node_56 76
Z21368_PEA_1_node_58 77
Z21368_PEA_1_node_66 78
Z21368_PEA_1_node_67 79
Z21368_PEA_1_node_69 80
Z21368_PEA_1_node_11 81
Z21368_PEA_1_node_12 82
Z21368_PEA_1_node_16 83
Z21368_PEA_1_node_17 84
Z21368_PEA_1_node_23 85
Z21368_PEA_1_node_24 86
Z21368_PEA_1_node_30 87
Z21368_PEA_1_node_31 88
Z21368_PEA_1_node_38 89
Z21368_PEA_1_node_47 90
Z21368_PEA_1_node_49 91
Z21368_PEA_1_node_51 92
Z21368_PEA_1_node_61 93
Z21368_PEA_1_node_68 94
Z21368_PEA_1_node_7 95

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
Z21368_PEA_1_P2 97
Z21368_PEA_1_P5 98
Z21368_PEA_1_P15 99
Z21368_PEA_1_P16 100
Z21368_PEA_1_P22 101
Z21368_PEA_1_P23 102

These sequences are variants of the known protein Extracellular sulfatase Sulf-1 precursor (SwissProt accession identifier SUL1_HUMAN; known also according to the synonyms EC 3.1.6.-; HSulf-1), SEQ ID NO:96, referred to herein as the previously known protein.

Protein Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) is known or believed to have the following function(s): Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation. The sequence for protein Extracellular sulfatase Sulf-1 precursor is given at the end of the application, as “Extracellular sulfatase Sulf-1 precursor amino acid sequence” (SEQ ID NO:96). Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
87-88 CC->AA: LOSS OF ARYLSULFATASE
ACTIVITY AND LOSS OF ABILITY TO
MODULATE APOPTOSIS.
 49 L -> P
728 K -> R

Protein Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) localization is believed to be Endoplasmic reticulum and Golgi stack; also localized on the cell surface (By similarity).

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: apoptosis; metabolism; heparan sulfate proteoglycan metabolism, which are annotation(s) related to Biological Process; arylsulfatase; hydrolase, which are annotation(s) related to Molecular Function; and extracellular space; endoplasmic reticulum; Golgi apparatus, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http:H/www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster Z21368 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of FIG. 12 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 12 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

TABLE 5
Normal tissue distribution
Name of Tissue Number
bladder 123
Bone 557
Brain 34
Colon 94
epithelial 56
general 68
head and neck 0
kidney 35
Lung 22
lymph nodes 0
breast 52
muscle 31
ovary 0
pancreas 0
prostate 44
skin 67
stomach 109
T cells 0
Thyroid 0
uterus 140

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
bladder 5.4e−01 6.6e−01 6.4e−01 1.0 8.5e−01 0.7
bone 4.5e−01 8.2e−01 9.1e−01 0.4 1 0.3
brain 5.5e−01 7.3e−01 1.5e−01 1.5 5.0e−01 0.9
colon 1.4e−01 2.8e−01 1.0e−01 2.0 3.0e−01 1.4
epithelial 1.1e−03 1.5e−01 1.2e−07 2.1 1.0e−01 1.1
general 1.4e−05 5.3e−02 1.9e−06 1.6 6.7e−01 0.8
head and neck 2.4e−02 7.1e−02 4.6e−01 2.5 7.5e−01 1.4
kidney 8.9e−01 9.0e−01 1 0.4 1 0.4
lung 3.5e−01 4.1e−01 7.2e−03 2.6 1.0e−01 1.6
lymph nodes 7.7e−02 3.1e−01 2.3e−02 8.5 1.9e−01 3.2
breast 4.0e−01 6.1e−01 5.4e−02 2.3 3.0e−01 1.3
muscle 7.5e−02 3.5e−02 1 1.0 1.7e−01 1.7
ovary 3.8e−01 4.2e−01 2.2e−01 2.9 3.4e−01 2.2
pancreas 2.2e−02 6.9e−02 1.4e−08 6.5 1.4e−06 4.6
prostate 8.3e−01 8.9e−01 3.1e−01 1.4 5.2e−01 1.1
skin 6.1e−01 8.1e−01 6.0e−01 1.2 1 0.3
stomach 4.4e−02 5.0e−01 5.0e−01 0.8 9.7e−01 0.4
T cells 5.0e−01 6.7e−01 3.3e−01 3.1 7.2e−01 1.4
Thyroid 3.6e−01 3.6e−01 1 1.1 1 1.1
uterus 3.5e−01 7.8e−01 4.6e−01 0.9 9.1e−01 0.5

As noted above, cluster Z21368 features 7 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96). A description of each variant protein according to the present invention is now provided.

Variant protein Z21368_PEA—1_P2 (SEQ ID NO:97) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA—1_T5 (SEQ ID NO:59). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z21368_PEA—1_P2 (SEQ ID NO:97) and SUL1_HUMAN (SEQ ID NO:96):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P2 (SEQ ID NO:97), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGK LRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNO GTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQ ASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYI DKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKE AAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWN corresponding to amino acids 1-761 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-761 of Z21368_PEA—1_P2 (SEQ ID NO:97), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) corresponding to amino acids 762-790 of Z21368_PEA—1_P2 (SEQ ID NO:97), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z21368_PEA—1_P2 (SEQ ID NO:97), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) in Z21368_PEA—1_P2 (SEQ ID NO:97).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z21368_PEA—1_P2 (SEQ ID NO:97) is encoded by the following transcript(s): Z21368_PEA—1_T5 (SEQ ID NO:59), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA—1_T5 (SEQ ID NO:59) is shown in bold; this coding portion starts at position 529 and ends at position 2898.

Variant protein Z21368_PEA—1_P5 (SEQ ID NO:98) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA—1_T9 (SEQ ID NO:61). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z21368_PEA—1_P5 (SEQ ID NO:98) and Q7Z2W2 (SEQ ID NO:840) (SEQ ID NO:840):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-57 of Z21368_PEA—1_P5 (SEQ ID NO:98), second bridging amino acid sequence comprising A, and a third amino acid sequence being at least 90% homologous to FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITN ESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNM DKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYT ADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDT PPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHL PKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNOGTPKYKPRFVHTRQTRSLSVEFE GEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT TVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKR RKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKER KEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNE THNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNOLHVQLMELRSCQGYKQCN PRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 139-871 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 59-791 of Z21368_PEA—1_P5 (SEQ ID NO:98), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise LAF having a structure as follows (numbering according to Z21368_PEA—1_P5 (SEQ ID NO:98)): a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 59+((n−2)−x), in which x varies from 0 to n−2.

Comparison report between Z21368_PEA—1_P5 (SEQ ID NO:98) and AAH12997 (SEQ ID NO:841) (SEQ ID NO:841):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNOGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNOLHVQLME (SEQ ID NO:1006) corresponding to amino acids 1-751 of Z21368_PEA—1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 1-40 of AAH12997 (SEQ ID NO:841), which also corresponds to amino acids 752-791 of Z21368_PEA—1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF (SEQ ID NO: 1006)
GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES
INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK
HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD
HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP
DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP
KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA
RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE
IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV
RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK
PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE
KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH
NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME
of Z21368_PEA_1_P5. (SEQ ID NO: 98)

Comparison report between Z21368_PEA—1_P5 (SEQ ID NO:98) and SUL1_HUMAN (SEQ ID NO:96):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-57 of Z21368_PEA—1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLIT NESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPN MDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGL DTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEES SKNIQQSN HLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNOGTPKYKPRFVHTRQTRSLSVE FEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGP PTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHL KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRK KERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRT VNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNOLHVQLMELRSCQGYK QCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 138-871 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 58-791 of Z21368_PEA—1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of Z21368_PEA—1_P5 (SEQ ID NO:98), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise LA, having a structure as follows: a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 58+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z21368_PEA—1_P5 (SEQ ID NO:98) is encoded by the following transcript(s): Z21368_PEA—1_T9 (SEQ ID NO:61), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA—1_T9 (SEQ ID NO:61) is shown in bold; this coding portion starts at position 556 and ends at position 2928.

Variant protein Z21368_PEA—1_P15 (SEQ ID NO:99) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA—1_T23 (SEQ ID NO:57). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z21368_PEA—1_P15 (SEQ ID NO:99) and SUL1_HUMAN (SEQ ID NO:96):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P15 (SEQ ID NO.99), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERG corresponding to amino acids 1-416 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-416 of Z21368_PEA—1_P15 (SEQ ID NO:99).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z21368_PEA—1_P15 (SEQ ID NO:99) is encoded by the following transcript(s): Z21368_PEA—1_T23 (SEQ ID NO:57), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA—1_T23 (SEQ ID NO:57) is shown in bold; this coding portion starts at position 691 and ends at position 1938.

Variant protein Z21368_PEA—1_P16 (SEQ ID NO:100) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA—1_T24 (SEQ ID NO:58). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z21368_PEA—1_P16 (SEQ ID NO:100) and SUL1_HUMAN (SEQ ID NO:96):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P16 (SEQ ID NO:100), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to amino acids 1-397 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-397 of Z21368_PEA—1_P 16 (SEQ ID NO:100), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) corresponding to amino acids 398-410 of Z21368_PEA—1_P16 (SEQ ID NO:100), wherein said first and second amino acid sequnes are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z21368_PEA—1_P 16 (SEQ ID NO:100), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) in Z21368_PEA—1_P16 (SEQ ID NO:100).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z21368_PEA—1_P16 (SEQ ID NO:100) is encoded by the following transcript(s): Z21368_PEA—1_T24 (SEQ ID NO:58), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA—1_T24 (SEQ ID NO:58) is shown in bold; this coding portion starts at position 691 and ends at position 1920.

Variant protein Z21368_PEA—1_P22 (SEQ ID NO:101) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA—1_T10 (SEQ ID NO:55) An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z21368_PEA—1_P22 (SEQ ID NO:101) and SUL1_HUMAN (SEQ ID NO:96):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P22 (SEQ ID NO:101), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAK corresponding to amino acids 1-188 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-188 of Z21368_PEA—1_P22 (SEQ ID NO:101), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) corresponding to amino acids 189-210 of Z21368_PEA—1_P22 (SEQ ID NO:101), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z21368_PEA—1_P22 (SEQ ID NO:101), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) in Z21368_PEA—1_P22 (SEQ ID NO:101).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z21368_PEA—1_P22 (SEQ ID NO:101) is encoded by the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA—1_T10 (SEQ ID NO:55) is shown in bold; this coding portion starts at position 691 and ends at position 1320.

Variant protein Z21368_PEA—1_P23 (SEQ ID NO:102) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA—1_T10 (SEQ ID NO:56). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z21368_PEA—1_P23 (SEQ ID NO:102) and Q7Z2W2 (SEQ ID NO:840):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-137 of Z21368_PEA—1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368_PEA—1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA—1_P23 (SEQ ID NO:102).

Comparison report between Z21368_PEA—1_P23 (SEQ ID NO:102) and SUL1_HUMAN (SEQ ID NO:96):

1. An isolated chimeric polypeptide encoding for Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-137 of Z21368_PEA—1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368_PEA—1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z21368_PEA—1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA—1_P23 (SEQ ID NO:102).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z21368_PEA—1_P23 (SEQ ID NO:102) is encoded by the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:56), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA—1_T11 (SEQ ID NO:56) is shown in bold; this coding portion starts at position 691 and ends at position 1125.

As noted above, cluster Z21368 features 34 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z21368_PEA—1_node—0 (SEQ ID NO:62) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T9 (SEQ ID NO:61). Table 7 below describes the starting and ending position of this segment on each transcript.

TABLE 7
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T9 (SEQ ID 1 327
NO: 61)

Segment cluster Z21368_PEA—1_node—15 (SEQ ID NO:63) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T10 (SEQ 631 807
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 631 807
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 631 807
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 631 807
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 469 645
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 469 645
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 496 672
NO: 61)

Segment cluster Z21368_PEA—1_node—19 (SEQ ID NO:64) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59) and Z21368_PEA—1_T6 (SEQ ID NO:60). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T10 (SEQ 863 1102
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 863 1102
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 863 1102
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 863 1102
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 701 940
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 701 940
NO: 60)

Segment cluster Z21368_PEA—1_node—2 (SEQ ID NO:65) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59) and Z21368_PEA—1_T6 (SEQ ID NO:60). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T10 (SEQ 1 300
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1 300
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1 300
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1 300
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1 300
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1 300
NO: 60)

Segment cluster Z21368_PEA—1_node—21 (SEQ ID NO:66) according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA 1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T10 (SEQ 1103 1254
ID NO: 55)
Z21368_PEA_1_T23 (SEQ 1103 1254
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1103 1254
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 941 1092
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 941 1092
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 728 879
NO: 61)

Segment cluster Z21368_PEA—1_node—33 (SEQ ID NO:67) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T10 (SEQ 1502 1677
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1424 1599
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1576 1751
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1576 1751
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1414 1589
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1414 1589
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1201 1376
NO: 61)

Segment cluster Z21368_PEA—1_node—36 (SEQ ID NO:68) according to the present invention is supported by 44 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment ending
Transcript name starting position position
Z21368_PEA_1_T10 (SEQ 1678 1806
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1600 1728
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1752 1880
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1752 1880
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1590 1718
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1590 1718
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1377 1505
NO: 61)

Segment cluster Z21368_PEA—1_node—37 (SEQ ID NO:69) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T24 (SEQ ID NO:58). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
Z21368_PEA_1_T24 1881 2159
(SEQ ID NO: 58)

Segment cluster Z21368_PEA—1_node—39 (SEQ ID NO:70) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T23 (SEQ ID NO:57) and Z21368_PEA—1_T24 (SEQ ID NO:58). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment
Transcript name Segment starting position ending position
Z21368_PEA_1_T23 (SEQ 1938 2790
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 2217 3069
ID NO: 58)

Segment cluster Z21368_PEA—1_node—4 (SEQ ID NO:71) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57) and Z21368_PEA—1_T24 (SEQ ID NO:58). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment
Transcript name Segment starting position ending position
Z21368_PEA_1_T10 (SEQ 301 462
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 301 462
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 301 462
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 301 462
ID NO: 58)

Segment cluster Z21368_PEA—1_node—41 (SEQ ID NO:72) according to the present invention is supported by 49 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 1864 1993
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1786 1915
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 1776 1905
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1776 1905
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1563 1692
NO: 61)

Segment cluster Z21368_PEA—1_node—43 (SEQ ID NO:73) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 1994 2210
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1916 2132
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 1906 2122
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1906 2122
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1693 1909
NO: 61)

Segment cluster Z21368_PEA—1_node—45 (SEQ ID NO:74) according to the present invention is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 2211 2466
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2133 2388
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2123 2378
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2123 2378
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1910 2165
NO: 61)

Segment cluster Z21368_PEA—1_node—53 (SEQ ID NO:75) according to the present invention is supported by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 2725 2900
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2647 2822
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2637 2812
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2637 2812
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2424 2599
NO: 61)

Segment cluster Z21368_PEA—1_node—56 (SEQ ID NO:76) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 2901 3043
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2823 2965
ID NO: 56)
Z21368_PEA_1_T9 (SEQ 2600 2742
ID NO: 61)

Segment cluster Z21368_PEA—1_node—58 (SEQ ID NO:77) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 3044 3167
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2966 3089
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2813 2936
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2813 2936
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2743 2866
NO: 61)

Segment cluster Z21368_PEA—1_node—66 (SEQ ID NO:78) according to the present invention is supported by 142 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56, Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 3202 3789
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 3124 3711
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2971 3558
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2971 3558
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2901 3488
NO: 61)

Segment cluster Z21368_PEA—1_node—67 (SEQ ID NO:79) according to the present invention is supported by 181 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 3790 4374
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 3712 4296
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 3559 4143
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 3559 4143
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 3489 4073
NO: 61)

Segment cluster Z21368_PEA—1_node—69 (SEQ ID NO:80) according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 4428 4755
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 4350 4677
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 4197 5384
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 4197 4524
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 4127 4454
NO: 61)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster Z21368_PEA—1_node—11 (SEQ ID NO:81) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 558 602
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 558 602
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 558 602
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 558 602
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 396 440
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 396 440
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 423 467
NO: 61)

Segment cluster Z21368_PEA—1_node—12 (SEQ ID NO:82) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56, Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1T9 (SEQ ID NO:61). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 603 630
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 603 630
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 603 630
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 603 630
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 441 468
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 441 468
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 468 495
NO: 61)

Segment cluster Z21368_PEA—1_node—16 (SEQ ID NO:83) according to the present invention can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 808 822
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 808 822
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 808 822
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 808 822
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 646 660
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 646 660
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 673 687
NO: 61)

Segment cluster Z21368_PEA—1_node—17 (SEQ ID NO:84) according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 823 862
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 823 862
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 823 862
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 823 862
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 661 700
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 661 700
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 688 727
NO: 61)

Segment cluster Z21368_PEA—1_node—23 (SEQ ID NO:85) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T11 (SEQ 1103 1176
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1255 1328
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1255 1328
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1093 1166
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1093 1166
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 880 953
NO: 61)

Segment cluster Z21368_PEA—1_node—24 (SEQ ID NO:86) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 1255 1350
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1177 1272
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1329 1424
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1329 1424
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1167 1262
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1167 1262
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 954 1049
NO: 61)

Segment cluster Z21368_PEA—1_node—30 (SEQ ID NO:87) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 1351 1409
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1273 1331
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1425 1483
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1425 1483
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1263 1321
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1263 1321
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1050 1108
NO: 61)

Segment cluster Z21368_PEA—1_node—31 (SEQ ID NO:88) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 1410 1501
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1332 1423
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1484 1575
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 1484 1575
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1322 1413
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1322 1413
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1109 1200
NO: 61)

Segment cluster Z21368_PEA—1_node—38 (SEQ ID NO:89) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 1807 1863
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 1729 1785
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 1881 1937
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 2160 2216
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 1719 1775
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 1719 1775
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 1506 1562
NO: 61)

Segment cluster Z21368_PEA—1_node—47 (SEQ ID NO:90) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 2467 2563
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2389 2485
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2379 2475
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2379 2475
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2166 2262
NO: 61)

Segment cluster Z21368_PEA—1_node—49 (SEQ ID NO 91) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 2564 2658
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2486 2580
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2476 2570
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2476 2570
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2263 2357
NO: 61)

Segment cluster Z21368_PEA—1_node—51 (SEQ ID NO:92) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 2659 2724
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 2581 2646
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2571 2636
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2571 2636
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2358 2423
NO: 61)

Segment cluster Z21368_PEA—1_node—61 (SEQ ID NO:93) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 3168 3201
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 3090 3123
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 2937 2970
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 2937 2970
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 2867 2900
NO: 61)

Segment cluster Z21368_PEA—1_node—68 (SEQ ID NO 94) according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 4375 4427
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 4297 4349
ID NO: 56)
Z21368_PEA_1_T5 (SEQ ID 4144 4196
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 4144 4196
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 4074 4126
NO: 61)

Segment cluster Z21368_PEA—1_node—7 (SEQ ID NO:95) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA—1_T10 (SEQ ID NO:55), Z21368_PEA—1_T11 (SEQ ID NO:56), Z21368_PEA—1_T23 (SEQ ID NO:57), Z21368_PEA—1_T24 (SEQ ID NO:58), Z21368_PEA—1_T5 (SEQ ID NO:59), Z21368_PEA—1_T6 (SEQ ID NO:60) and Z21368_PEA—1_T9 (SEQ ID NO:61). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
Z21368_PEA_1_T10 (SEQ 463 557
ID NO: 55)
Z21368_PEA_1_T11 (SEQ 463 557
ID NO: 56)
Z21368_PEA_1_T23 (SEQ 463 557
ID NO: 57)
Z21368_PEA_1_T24 (SEQ 463 557
ID NO: 58)
Z21368_PEA_1_T5 (SEQ ID 301 395
NO: 59)
Z21368_PEA_1_T6 (SEQ ID 301 395
NO: 60)
Z21368_PEA_1_T9 (SEQ ID 328 422
NO: 61)

Overexpression of at least a portion of this cluster was determined according to oligonucleotides and one or more chips. The results were as follows: Oligonucleotide Z21368—0—0—61857 was on the TAA chip and was found to be overexpressed in breast cancer.

Variant protein alignment to the previously known protein:

Sequence name: /tmp/5ER3vIMKE2/9L0Y7lDlTQ:SUL1_HUMAN (SEQ ID NO:96)

Sequence documentation:

Alignment of: Z21368_PEA—1_P2 (SEQ ID NO:97)×SUL1_HUMAN (SEQ ID NO:96).

Alignment segment 1/1:

Quality: 7664.00
Score: 0
Matching length: 761 Total length: 761
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .         .         .
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
         .         .         .         .         .
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
         .         .         .         .         .
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
         .         .         .         .         .
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
         .         .         .         .         .
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
         .         .         .         .         .
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
         .         .         .         .         .
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
         .         .         .         .         .
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
         .         .         .         .         .
501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
         .         .         .         .         .
551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
         .         .         .         .         .
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
         .         .         .         .         .
651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700
         .         .         .         .         .
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750
         .
751 NNHWQTAPFWN 761
|||||||||||
751 NNHWQTAPFWN 761

Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:Q7Z2W2 (SEQ ID NO:840)

Sequence documentation:

Alignment of: Z21368_PEA—1_P5 (SEQ ID NO:98)×Q7Z2W2 (SEQ ID NO:840).

Alignment segment 1/1:

Quality: 7869.00
Score: 0
Matching length: 791 Total length: 871
Matching Percent 99.87 Matching Percent Identity: 99.87
Similarity:
Total Percent Similarity: 90.70 Total Percent Identity: 90.70
Gaps: 1

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELA.......................................... 58
|||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFTNAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .         .         .
59 ......................................FFGKYLNEYNGS 70
                                      ||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTVFFGKYLNEYNGS 150
         .         .         .         .         .
71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 120
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
         .         .         .         .         .
121 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMYPHRPVMMVISHAAPRGPEDSAPQFSKLYPNASQHITPSYN 250
         .         .         .         .         .
171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
         .         .         .         .         .
221 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 270
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
         .         .         .         .         .
271 PGSIVPQIVLNIDLAPTILDTAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320
||||||||||||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
         .         .         .         .         .
321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370
||||||||||||||||||||||||||||||||||||||||||||||||||
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
         .         .         .         .         .
371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420
||||||||||||||||||||||||||||||||||||||||||||||||||
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
         .         .         .         .         .
421 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470
||||||||||||||||||||||||||||||||||||||||||||||||||
501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQRRSLSVEF 550
         .         .         .         .         .
471 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520
||||||||||||||||||||||||||||||||||||||||||||||||||
551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
         .         .         .         .         .
521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570
||||||||||||||||||||||||||||||||||||||||||||||||||
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
         .         .         .         .         .
571 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 620
||||||||||||||||||||||||||||||||||||||||||||||||||
651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700
         .         .         .         .         .
621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 670
||||||||||||||||||||||||||||||||||||||||||||||||||
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750
         .         .         .         .         .
671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720
||||||||||||||||||||||||||||||||||||||||||||||||||
751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800
         .         .         .         .         .
721 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 770
||||||||||||||||||||||||||||||||||||||||||||||||||
801 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 850
         .         .
771 GNKDGGSYDLHRGQLWDGWEG 791
|||||||||||||||||||||
851 GNKDGGSYDLHRGQLWDGWEG 871

Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:AAH12997 (SEQ ID NO:841)

Sequence documentation:

Alignment of: Z21368_PEA—1_P5 (SEQ ID NO:98)×AAH12997 (SEQ ID NO:841).

Alignment segment 1/1:

Quality: 420.00
Score: 0
Matching length: 40 Total length: 40
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .
752 LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG 791
||||||||||||||||||||||||||||||||||||||||
1 LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG 40

Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:SUL1_HUMAN (SEQ ID NO:96)

Sequence documentation:

Alignment of: Z21368_PEA—1_P5 (SEQ ID NO:98)×SUL1_HUMAN (SEQ ID NO:96).

Alignment segment 1/1:

Quality: 7878.00
Score: 0
Matching length: 791 Total length: 871
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 90.82 Total Percent Identity: 90.82
Gaps: 1

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVEL........................................... 57
|||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .         .         .
58 .....................................AFFGKYLNEYNGS 70
                                     |||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
         .         .         .         .         .
71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 120
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
         .         .         .         .         .
121 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
         .         .         .         .         .
171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
         .         .         .         .         .
221 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 270
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
         .         .         .         .         .
271 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320
||||||||||||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
         .         .         .         .         .
321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370
||||||||||||||||||||||||||||||||||||||||||||||||||
401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450
         .         .         .         .         .
371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420
||||||||||||||||||||||||||||||||||||||||||||||||||
451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500
         .         .         .         .         .
421 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470
||||||||||||||||||||||||||||||||||||||||||||||||||
501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550
         .         .         .         .         .
471 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520
||||||||||||||||||||||||||||||||||||||||||||||||||
551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600
         .         .         .         .         .
521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570
||||||||||||||||||||||||||||||||||||||||||||||||||
601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650
         .         .         .         .         .
571 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 620
||||||||||||||||||||||||||||||||||||||||||||||||||
651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700
         .         .         .         .         .
621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 670
||||||||||||||||||||||||||||||||||||||||||||||||||
701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750
         .         .         .         .         .
671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720
||||||||||||||||||||||||||||||||||||||||||||||||||
751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800
         .         .         .         .         .
721 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 770
||||||||||||||||||||||||||||||||||||||||||||||||||
801 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 850
         .         .
771 GNKDGGSYDLHRGQLWDGWEG 791
|||||||||||||||||||||
851 GNKDGGSYDLHRGQLWDGWEG 871

Sequence name: /tmp/AVAZGWHuF0/RzHFOnHIsT:SUL1_HUMAN (SEQ ID NO:96)

Sequence documentation:

Alignment of: Z21368_PEA—1_P15 (SEQ ID NO:99)×SUL1_HUMAN (SEQ ID NO:96).

Alignment segment 1/1:

Quality: 4174.00
Escore: 0
Matching length: 416 Total length: 416
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .         .         .
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
         .         .         .         .         .
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
         .         .         .         .         .
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
         .         .         .         .         .
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
         .         .         .         .         .
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
         .         .         .         .         .
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400
         .
401 NKKAKIWRDTFLVERG 416
||||||||||||||||
401 NKKAKIWRDTFLVERG 416

Sequence name: /tmp/JhwgRdKqmt/kqSmjxkWWk:SUL1_HUMAN (SEQ ID NO:96)

Sequence documentation:

Alignment of: Z21368_PEA—1_P16 (SEQ ID NO:100)×SUL1_HUMAN (SEQ ID NO:96).

Alignment segment 1/1:

Quality: 3985.00
Escore: 0
Matching length: 397 Total length: 397
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .         .         .
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
         .         .         .         .         .
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200
         .         .         .         .         .
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250
         .         .         .         .         .
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300
         .         .         .         .         .
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350
         .         .         .         .
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR 397
|||||||||||||||||||||||||||||||||||||||||||||||
351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR 397

Sequence name: /tmp/GPlnIw3BOg/zXFdxqG4ow:SUL1_HUMAN (SEQ ID NO:96)

Sequence documentation:

Alignment of: Z21368_PEA—1_P22 (SEQ ID NO:101)×SUL1_HUMAN (SEQ ID NO:96).

Alignment segment 1/1:

Quality: 1897.00
Escore: 0
Matching length: 188 Total length: 188
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .         .         .
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150
         .         .         .
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188
||||||||||||||||||||||||||||||||||||||
151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188

Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:Q7Z2W2 (SEQ ID NO:840)

Sequence documentation:

Alignment of: Z21368_PEA—1_P23 (SEQ ID NO:102)×Q7Z2W2 (SEQ ID NO:840).

Alignment segment 1/1:

Quality: 1368.00
Escore: 0.000511
Matching length: 137 Total length: 137
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137
|||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137

Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:SUL1_HUMAN (SEQ ID NO:96)

Sequence documentation:

Alignment of: Z21368_PEA—1_P23 (SEQ ID NO:102)×SUL1_HUMAN (SEQ ID NO:96).

Alignment segment 1/1:

Quality: 1368.00
Escore: 0.000511
Matching length: 137 Total length: 137
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50
         .         .         .         .         .
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100
         .         .         .
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137
|||||||||||||||||||||||||||||||||||||
101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137

Expression of SUL1_HUMAN—Extracellular Sulfatase Sulf-1Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368seg39 (SEQ ID NO:844) in Normal and Cancerous Breast Tissues

Expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by or according to seg39, Z21368seg39 (SEQ ID NO:844) amplicon and Z21368seg39F (SEQ ID NO:842) and Z21368seg39R (SEQ ID NO:843) primers was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926), amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60,63-67, Table 1 above, Tissue samples in testing panel), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 13 is a histogram showing over expression of the above-indicated SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5-fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 13, the expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 56-60,63-67, Table 1 above, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 13 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 2.14E-03.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.91E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z21368seg39F forward primer (SEQ ID NO:842); Z21368seg39R reverse primer (SEQ ID NO:843).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z21368seg39 (SEQ ID NO:844).

Z21368seg39F (SEQ ID NO: 842)-
GTTGCATTTCTCAGTGCTGGTTT
Z21368seg39R (SEQ ID NO: 843)-
AGGGTGCCGGGTGAGG
Z21368seg39 (SEQ ID NO: 844)-
GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGATTGAGTTTCTCTACCATC
CTCCCCACGTTCTTCTCTAAGCTGCCTCCAAGCCTCACCCGGCACCCT

Expression of SUL1_HUMAN—Extracellular Sulfatase Sulf-1Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368seg39 (SEQ ID NO:844) in Different Normal Tissues

Expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by or according to Z21368seg39 (SEQ ID NO:844) amplicon and Z21368seg39F (SEQ ID NO:842) Z21368seg39R (SEQ ID NO:843) was measured by real time PCR. In parallel the expression of four housekeeping genes—[RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (sample nos. 33-35 in table 2 “Tissue samples in normal panel”) to obtain a value of relative expression of each sample relative to median of the Normal samples. Primers and amplicon are as above.

The results are presented in FIG. 14, demonstrating the expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39 (SEQ ID NO:844), in different normal tissues.

Expression of SUL1_HUMAN—Extracellular Sulfatase Sulf-1Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368junc17-21 (SEQ ID NO:847) in Normal and Cancerous Breast Tissues

Expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by or according to Z21368junc17-21 (SEQ ID NO:847) amplicon and Z21368junc17-21F (SEQ ID NO:845) and Z21368junc17-21R (SEQ ID NO:846) primers was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos 56-60,63-67 Table 1 above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 15 is a histogram showing over expression of the above-indicated SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 15, the expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 56-60,63-67, Table 1 above, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 11 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of SUL1_HUMAN—Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 4.6E-03.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.78E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z21368junc17-21F forward primer (SEQ ID NO:845); Z21368junc17-21R reverse primer (SEQ ID NO:846).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z21368junc17-21 (SEQ ID NO:847)

Z21368junc17-21F (SEQ ID NO: 845)-
GGACGGATACAGCAGGAACG
Z21368junc17-21R (SEQ ID NO: 846)-
TATTTTCCAAAAAAGGCCAGCTC
Z21368junc17-21 (SEQ ID NO: 847)-
GGACGGATACAGCAGGAACGAAAAAACATCCGACCCAACATTATTCTTGTGCTTAC
CGATGATCAAGATGTGGAGCTGGCCTTTTTTGGAAAATA

Expression of SUL1_HUMAN—Extracellular Sulfatase Sulf-1 Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368junc17-21 (SEQ ID NO:847) in Different Normal Tissues

Expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 Z21368 transcripts detectable by or according to amplicon Z21368junc17-21 (SEQ ID NO:847) was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes, as above. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos.—33-35 Table 2 above, “Tissue samples on normal panel”), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above.

The results are presented in FIG. 16, demonstrating the expression of SUL1_HUMAN—Extracellular sulfatase Sulf-1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368junc17-21 (SEQ ID NO:847), in different normal tissues.

Description for Cluster T59832

Cluster T59832 features 6 transcript(s) and 33 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the 5 application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No
T59832_T11 103
T59832_T15 104
T59832_T22 105
T59832_T28 106
T59832_T6 107
T59832_T8 108

TABLE 2
Segments of interest
Segment Name Sequence ID No
T59832_node_1 109
T59832_node_22 110
T59832_node_23 111
T59832_node_24 112
T59832_node_29 113
T59832_node_39 114
T59832_node_7 115
T59832_node_10 116
T59832_node_11 117
T59832_node_12 118
T59832_node_14 119
T59832_node_16 120
T59832_node_19 121
T59832_node_2 122
T59832_node_20 123
T59832_node_25 124
T59832_node_26 125
T59832_node_27 126
T59832_node_28 127
T59832_node_3 128
T59832_node_30 129
T59832_node_31 130
T59832_node_32 131
T59832_node_34 132
T59832_node_35 133
T59832_node_36 134
T59832_node_37 135
T59832_node_38 136
T59832_node_4 137
T59832_node_5 138
T59832_node_6 139
T59832_node_8 140
T59832_node_9 141

TABLE 3
Proteins of interest
Protein Name Sequence ID No
T59832_P5 143
T59832_P7 144
T59832_P9 145
T59832_P12 146
T59832_P18 147

These sequences are variants of the known protein Gamma-interferon inducible lysosomal thiol reductase precursor (SwissProt accession identifier GILT_HUMAN; known also according to the synonyms Gamma-interferon-inducible protein IP-30), SEQ ID NO: 142, referred to herein as the previously known protein.

Protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) is known or believed to have the following function(s): Cleaves disulfide bonds in proteins by reduction. May facilitate the complet unfolding of proteins destined for lysosomal degradation. May be involved in MHC class II-restricted antigen processing. The sequence for protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) is given at the end of the application, as “Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
109 L -> S
130 H -> L

Protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) localization is believed to be Lysosomal.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: extracellular; lysosome, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster T59832 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 17 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 17 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

TABLE 5
Normal tissue distribution
Name of Tissue Number
Adrenal 208
Bladder 205
Bone 200
Brain 18
Colon 236
Epithelial 143
General 280
head and neck 192
Kidney 71
Liver 53
Lung 459
lymph nodes 248
Breast 0
bone marrow 94
Ovary 0
Pancreas 20
Prostate 86
Skin 29
Stomach 109
T cells 557
Thyroid 0
Uterus 63

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 4.9e−01 5.9e−01 4.7e−03 1.1 2.9e−02 0.8
bladder 3.7e−01 5.6e−01 3.7e−02 1.3 2.5e−01 0.9
Bone 6.6e−01 6.7e−01 3.4e−01 0.6 9.1e−01 0.4
Brain 1.8e−01 2.9e−01 4.3e−03 3.8 2.8e−02 2.5
colon 4.4e−01 5.2e−01 6.1e−01 0.9 8.1e−01 0.7
epithelial 2.5e−02 1.6e−01 1.2e−05 1.6 9.8e−02 1.1
general 1.3e−02 1.6e−01 1 0.8 1 0.6
Head and neck 3.4e−01 3.3e−01 1 0.4 9.4e−01 0.5
kidney 7.7e−01 8.5e−01 1.4e−01 1.3 4.2e−01 0.9
Liver 8.3e−01 7.6e−01 1 0.5 1 0.6
Lung 5.7e−01 8.3e−01 3.5e−01 0.8 9.8e−01 0.5
lymph nodes 5.7e−01 6.6e−01 7.6e−01 0.8 3.6e−02 1.1
breast 5.0e−02 1.3e−01 2.5e−03 6.5 4.4e−02 3.6
Bone marrow 6.2e−01 7.8e−01 1 0.3 9.5e−01 0.5
ovary 2.2e−01 9.4e−02 3.2e−03 6.1 8.3e−03 5.3
pancreas 9.0e−02 1.6e−02 1.1e−03 4.0 7.9e−04 4.2
prostate 8.1e−01 8.0e−01 5.7e−01 0.9 4.1e−01 0.9
skin 1.6e−01 1.2e−01 2.3e−02 6.0 1.0e−02 2.2
stomach 5.5e−01 7.4e−01 9.4e−01 0.6 4.9e−01 1.0
T cells 1 6.7e−01 6.9e−01 1.0 9.8e−01 0.5
Thyroid 2.3e−01 2.3e−01 5.9e−02 2.5 5.9e−02 2.5
uterus 7.4e−02 4.7e−02 2.2e−02 2.0 6.2e−02 1.7

As noted above, cluster T59832 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142). A description of each variant protein according to the present invention is now provided.

Variant protein T59832_P5 (SEQ ID NO:143) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T6 (SEQ ID NO:107). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application.

Comparison report between T59832_P5 (SEQ ID NO:143) and GILT_HUMAN (SEQ ID NO:142):

1. An isolated chimeric polypeptide encoding for T59832_P5 (SEQ ID NO:143), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P5 (SEQ ID NO:143), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG (SEQ ID NO:1010) corresponding to amino acids 45-189 of T59832_P5 (SEQ ID NO:143), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P5 (SEQ ID NO:143), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP (SEQ ID NO: 1010)
SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL
AATLDAFIPARAGLACLWDLLGRCPRG
in T59832_P5. (SEQ ID NO: 143)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T59832_P5 (SEQ ID NO:143) is encoded by the following transcript(s): T59832_T6 (SEQ ID NO:107), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T6 (SEQ ID NO:107) is shown in bold; this coding portion starts at position 149 and ends at position 715. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P5 (SEQ ID NO:143) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
61 C -> T Yes
148 G -> T Yes
1505 G -> C Yes
1651 T -> No
1652 T -> G Yes
1717 C -> A No
1722 C -> No
1722 C -> G No
1752 A -> G Yes
1817 A -> G Yes
1854 C -> No
1854 C -> A No
212 -> A No
1871 C -> T Yes
1886 T -> G No
1906 G -> A No
1906 G -> C No
1942 C -> No
1942 C -> T No
1971 C -> No
1986 G -> A No
2001 G -> T Yes
2008 A -> No
241 G -> T No
2030 -> T No
2031 C -> T No
2050 C -> No
2056 A -> G Yes
2068 G -> A Yes
2111 A -> C Yes
2136 A -> C Yes
2144 T -> C Yes
244 A -> G Yes
962 C -> T Yes
1074 G -> A Yes
1248 G -> C Yes
1441 G -> A Yes
1443 G -> A No

Variant protein T59832_P7 (SEQ ID NO:144) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T8 (SEQ ID NO:108). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T59832_P7 (SEQ ID NO:144) and GILT_HUMAN (SEQ ID NO:142):

1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 12-223 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

Comparison report between T59832_P7 (SEQ ID NO:144) and BAC98466 (SEQ ID NO:848):

1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

Comparison report between T59832_P7 (SEQ ID NO:144) and BAC85622 (SEQ ID NO:849):

1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 1-148 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012)
PLVNVTLYYEALCGGCRAFLIRELFPTWLLV
of T59832_P7. (SEQ ID NO: 144)

Comparison report between T59832_P7 (SEQ ID NO:144) and Q8WU77 (SEQ ID NO:850):

1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide.

Variant protein T59832_P7 (SEQ ID NO:144) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P7 (SEQ ID NO:144) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
146 I -> No
146 I -> M Yes
168 P -> Q No
170 L -> No
170 L -> V No
180 M -> V Yes
76 R -> Q Yes
77 A -> T No

Variant protein T59832_P7 (SEQ ID NO:144) is encoded by the following transcript(s): T59832_T8 (SEQ ID NO:108), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T8 (SEQ ID NO:108) is shown in bold; this coding portion starts at position 149 and ends at position 862. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P7 (SEQ ID NO:144) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
61 C -> T Yes
148 G -> T Yes
651 C -> A No
656 C -> No
656 C -> G No
686 A -> G Yes
751 A -> G Yes
1004 T -> G Yes
1206 C -> No
1206 C -> A No
1223 C -> T Yes
1238 T -> G No
212 -> A No
1258 G -> A No
1258 G -> C No
1294 C -> No
1294 C -> T No
1323 C -> No
1338 G -> A No
1353 G -> T Yes
1360 A -> No
1382 -> T No
1383 C -> T No
241 G -> T No
1402 C -> No
1408 A -> G Yes
1420 G -> A Yes
1463 A -> C Yes
1488 A -> C Yes
1496 T -> C Yes
244 A -> G Yes
375 G -> A Yes
377 G -> A No
439 G -> C Yes
585 T -> No
586 T -> G Yes

Variant protein T59832_P9 (SEQ ID NO:145) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T11 (SEQ ID NO:103). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T59832_P9 (SEQ ID NO:145) and GILT_HUMAN (SEQ ID NO:2):

1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 12-214 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

Comparison report between-T59832_P9 (SEQ ID NO:145) and BAC98466 (SEQ ID NO:848):

1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

Comparison report between T59832_P9 (SEQ ID NO:145) and BAC85622 (SEQ ID NO:849):

1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P9 (SEQ ID NO:145), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-113 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-203 of T59832_P9 (SEQ ID NO:145), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012)
PLVNVTLYYEALCGGCRAFLIRELFPTWLLV
of T59832_P9. (SEQ ID NO: 145)

3. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

Comparison report between T59832_P9 (SEQ ID NO:145) and Q8WU77 (SEQ ID NO:850):

1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

(SEQ ID NO: 1013)
NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR

corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T59832_P9 (SEQ ID NO:145) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P9 SEQ ID NO:145) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
146 I -> No
146 I -> M Yes
222 A -> P No
222 A -> T No
234 P -> No
234 P -> S No
243 G -> No
76 R -> Q Yes
77 A -> T No
168 P -> Q No
170 L -> No
170 L -> V No
180 M -> V Yes
204 N -> No
204 N -> K No
210 P -> L Yes
215 L -> W No

Variant protein T59832_P9 (SEQ ID NO:145) is encoded by the following transcript(s): T59832_T11 (SEQ ID NO:103), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T11 (SEQ ID NO:103) is shown in bold; this coding portion starts at position 149 and ends at position 880. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P9 (SEQ ID NO:145) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
61 C -> T Yes
148 G -> T Yes
651 C -> A No
656 C -> No
656 C -> G No
686 A -> G Yes
751 A -> G Yes
760 C -> No
760 C -> A No
777 C -> T Yes
792 T -> G No
812 G -> A No
212 -> A No
812 G -> C No
848 C -> No
848 C -> T No
877 C -> No
892 G -> A No
907 G -> T Yes
914 A -> No
936 -> T No
937 C -> T No
956 C -> No
241 G -> T No
962 A -> G Yes
974 G -> A Yes
1017 A -> C Yes
1042 A -> C Yes
1050 T -> C Yes
244 A -> G Yes
375 G -> A Yes
377 G -> A No
439 G -> C Yes
585 T -> No
586 T -> G Yes

Variant protein T59832_P12 (SEQ ID NO:146) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T15 (SEQ ID NO:104). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T59832_P12 (SEQ ID NO:146) and GILT_HUMAN (SEQ ID NO:142):

1. An isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 12-141 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n−2)−x), in which x varies from 0 to n−2.

Comparison report between T59832_P12 (SEQ ID NO:146) and BAC85622 (SEQ ID NO:849):

1. An isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P12 (SEQ ID NO:146), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE corresponding to amino acids 1-40 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-130 of T59832_P12 (SEQ ID NO:146), third amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 72-122 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 131-181 of T59832_P12 (SEQ ID NO:146), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK (SEQ ID NO:1016) corresponding to amino acids 182-219 of T59832_P12 (SEQ ID NO:146), wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of T59832_P12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012)
PLVNVTLYYEALCGGCRAFLIRELFPTWLLV
of T59832_P12. (SEQ ID NO: 146)

3. An isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n−2)−x), in which x varies from 0 to n−2.

4. An isolated polypeptide encoding for a tail of T59832_P12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK (SEQ ID NO:1016) in T59832_P12 (SEQ ID NO:146).

Comparison report between T59832_P12 (SEQ ID NO:146) and Q8WU77 (SEQ ID NO:850):

1. An isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 1-130 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T59832_P12 (SEQ ID NO:146) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P12 (SEQ ID NO:146) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
137 P -> Q No
139 L -> No
76 R -> Q Yes
77 A -> T No
139 L -> V No
149 M -> V Yes
183 P -> No
183 P -> T No
200 G -> A No
200 G -> D No
212 S -> No
212 S -> F No

Variant protein T59832_P12 (SEQ ID NO:146) is encoded by the following transcript(s): T59832_T15 (SEQ ID NO:104), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T15 (SEQ ID NO:104) is shown in bold; this coding portion starts at position 149 and ends at position 805. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P12 (SEQ ID NO:146) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
61 C -> T Yes
148 G -> T Yes
563 C -> G No
593 A -> G Yes
658 A -> G Yes
695 C -> No
695 C -> A No
712 C -> T Yes
727 T -> G No
747 G -> A No
747 G -> C No
783 C -> No
212 -> A No
783 C -> T No
812 C -> No
827 G -> A No
842 G -> T Yes
849 A -> No
871 -> T No
872 C -> T No
891 C -> No
897 A -> G Yes
909 G -> A Yes
241 G -> T No
952 A -> C Yes
977 A -> C Yes
985 T -> C Yes
244 A -> G Yes
375 G -> A Yes
377 G -> A No
439 G -> C Yes
558 C -> A No
563 C -> No

Variant protein T59832_P18 (SEQ ID NO:147) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T22 (SEQ ID NO:105). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T59832_P18 (SEQ ID NO:147) and GILT_HUMAN (SEQ ID NO:142):

1. An isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n−2)−x), in which x varies from 0 to n−2.

Comparison report between T59832_P18 (SEQ ID NO:147) and Q8WU77 (SEQ ID NO:850):

1. An isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n−2)−x), in which x varies from 0 to n−2.

Comparison report between T59832_P18 (SEQ ID NO:147) and Q8NE14 (SEQ ID NO:851):

1. An isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T59832_P18 (SEQ ID NO:147) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P18 (SEQ ID NO:147) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
114 G -> A No
114 G -> D No
126 S -> No
126 S -> F No
51 P -> Q No
53 L -> No
53 L -> V No
63 M -> V Yes
97 P -> No
97 P -> T No

Variant protein T59832_P18 (SEQ ID NO:147) is encoded by the following transcript(s): T59832_T22 (SEQ ID NO:105), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T22 (SEQ ID NO:105) is shown in bold; this coding portion starts at position 149 and ends at position 547. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P18 (SEQ ID NO:147) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
61 C -> T Yes
148 G -> T Yes
437 C -> No
437 C -> A No
454 C -> T Yes
469 T -> G No
489 G -> A No
489 G -> C No
525 C -> No
525 C -> T No
554 C -> No
569 G -> A No
212 -> A No
584 G -> T Yes
591 A -> No
613 -> T No
614 C -> T No
633 C -> No
639 A -> G Yes
651 G -> A Yes
694 A -> C Yes
719 A -> C Yes
727 T -> C Yes
241 G -> T No
244 A -> G Yes
300 C -> A No
305 C -> No
305 C -> G No
335 A -> G Yes
400 A -> G Yes

As noted above, cluster T59832 features 33 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T59832_node—1 (SEQ ID NO:109) according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 1 123
NO: 103)
T59832_T15 (SEQ ID 1 123
NO: 104)
T59832_T22 (SEQ ID 1 123
NO: 105)
T59832_T6 (SEQ ID NO: 107) 1 123
T59832_T8 (SEQ ID NO: 108) 1 123

Segment cluster T59832_node—22 (SEQ ID NO:110) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28 (SEQ ID NO:106). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T28 (SEQ ID 1 523
NO: 106)

Segment cluster T59832_node—23 (SEQ ID NO:111) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28 (SEQ ID NO:106). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T28 (SEQ ID 524 652
NO: 106)

Segment cluster T59832_node—24 (SEQ ID NO:112) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28 (SEQ ID NO:106). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T28 (SEQ ID 653 901
NO: 106)

Segment cluster T59832_node—29 (SEQ ID NO:113) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T28 (SEQ ID NO:106) and T59832_T8 (SEQ ID NO:108). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T28 (SEQ ID 1055 1472
NO: 106)
T59832_T8 (SEQ ID NO: 108) 785 1202

Segment cluster T59832_node—39 (SEQ ID NO:114) according to the present invention is supported by 195 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 1031 1084
NO: 103)
T59832_T15 (SEQ ID 966 1019
NO: 104)
T59832_T22 (SEQ ID 708 761
NO: 105)
T59832_T28 (SEQ ID 1747 1800
NO: 106)
T59832_T6 (SEQ ID NO: 107) 2125 2178
T59832_T8 (SEQ ID NO: 108) 1477 1530

Segment cluster T59832_node—7 (SEQ ID NO:115) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T6 (SEQ ID NO:107). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T6 (SEQ ID NO: 107) 281 1346

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster T59832_node—10 (SEQ ID NO:116) according to the present invention is supported by 332 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 338 382
NO: 103)
T59832_T15 (SEQ ID 338 382
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1404 1448
T59832_T8 (SEQ ID NO: 108) 338 382

Segment cluster T59832_node—11 (SEQ ID NO:117) according to the present invention is supported by 306 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 383 417
NO: 103)
T59832_T15 (SEQ ID 383 417
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1449 1483
T59832_T8 (SEQ ID NO: 108) 383 417

Segment cluster T59832_node—12 (SEQ ID NO:118) according to the present invention is supported by 280 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 418 463
NO: 103)
T59832_T15 (SEQ ID 418 463
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1484 1529
T59832_T8 (SEQ ID NO: 108) 418 463

Segment cluster T59832_node—14 (SEQ ID NO:119) according to the present invention is supported by 280 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 464 502
NO: 103)
T59832_T15 (SEQ ID 464 502
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1530 1568
T59832_T8 (SEQ ID NO: 108) 464 502

Segment cluster T59832_node—16 (SEQ ID NO:120) according to the present invention is supported by 287 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 503 538
NO: 103)
T59832_T15 (SEQ ID 503 538
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1569 1604
T59832_T8 (SEQ ID NO: 108) 503 538

Segment cluster T59832_node—19 (SEQ ID NO:121) according to the present invention is supported by 300 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 539 577
NO: 103)
T59832_T6 (SEQ ID NO: 107) 1605 1643
T59832_T8 (SEQ ID NO: 108) 539 577

Segment cluster T59832_node—2 (SEQ ID NO:122) according to the present invention is supported by 258 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 124 154
NO: 103)
T59832_T15 (SEQ ID 124 154
NO: 104)
T59832_T22 (SEQ ID 124 154
NO: 105)
T59832_T6 (SEQ ID NO: 107) 124 154
T59832_T8 (SEQ ID NO: 108) 124 154

Segment cluster T59832_node—20 (SEQ ID NO:123) according to the present invention is supported by 318 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 578 631
NO: 103)
T59832_T6 (SEQ ID NO: 107) 1644 1697
T59832_T8 (SEQ ID NO: 108) 578 631

Segment cluster T59832_node—25 (SEQ ID NO:124) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 632 653
NO: 103)
T59832_T15 (SEQ ID 539 560
NO: 104)
T59832_T22 (SEQ ID 281 302
NO: 105)
T59832_T28 (SEQ ID 902 923
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1698 1719
T59832_T8 (SEQ ID NO: 108) 632 653

Segment cluster T59832_node—26 (SEQ ID NO:125) according to the present invention is supported by 342 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 654 717
NO: 103)
T59832_T15 (SEQ ID 561 624
NO: 104)
T59832_T22 (SEQ ID 303 366
NO: 105)
T59832_T28 (SEQ ID 924 987
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1720 1783
T59832_T8 (SEQ ID NO: 108) 654 717

Segment cluster T59832_node—27 (SEQ ID NO:126) according to the present invention is supported by 314 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 718 756
NO: 103)
T59832_T15 (SEQ ID 625 663
NO: 104)
T59832_T22 (SEQ ID 367 405
NO: 105)
T59832_T28 (SEQ ID 988 1026
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1784 1822
T59832_T8 (SEQ ID NO: 108) 718 756

Segment cluster T59832_node—28 (SEQ ID NO:127) according to the present invention is supported by 284 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T15 (SEQ ID 664 691
NO: 104)
T59832_T22 (SEQ ID 406 433
NO: 105)
T59832_T28 (SEQ ID 1027 1054
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1823 1850
T59832_T8 (SEQ ID NO: 108) 757 784

Segment cluster T59832_node—3 (SEQ ID NO:128) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 155 172
NO: 103)
T59832_T15 (SEQ ID 155 172
NO: 104)
T59832_T22 (SEQ ID 155 172
NO: 105)
T59832_T6 (SEQ ID NO: 107) 155 172
T59832_T8 (SEQ ID NO: 108) 155 172

Segment cluster T59832_node—30 (SEQ ID NO:129) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 757 760
NO: 103)
T59832_T15 (SEQ ID 692 695
NO: 104)
T59832_T22 (SEQ ID 434 437
NO: 105)
T59832_T28 (SEQ ID 1473 1476
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1851 1854
T59832_T8 (SEQ ID NO: 108) 1203 1206

Segment cluster T59832_node—31 (SEQ ID NO:130) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 761 780
NO: 103)
T59832_T15 (SEQ ID 696 715
NO: 104)
T59832_T22 (SEQ ID 438 457
NO: 105)
T59832_T28 (SEQ ID 1477 1496
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1855 1874
T59832_T8 (SEQ ID NO: 108) 1207 1226

Segment cluster T59832_node—32 (SEQ ID NO:131) according to the present invention is supported by 287 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 781 810
NO: 103)
T59832_T15 (SEQ ID 716 745
NO: 104)
T59832_T22 (SEQ ID 458 487
NO: 105)
T59832_T28 (SEQ ID 1497 1526
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1875 1904
T59832_T8 (SEQ ID NO: 108) 1227 1256

Segment cluster T59832_node—34 (SEQ ID NO:132) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 811 832
NO: 103)
T59832_T15 (SEQ ID 746 767
NO: 104)
T59832_T22 (SEQ ID 488 509
NO: 105)
T59832_T28 (SEQ ID 1527 1548
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1905 1926
T59832_T8 (SEQ ID NO: 108) 1257 1278

Segment cluster T59832_node—35 (SEQ ID NO:133) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 833 836
NO: 103)
T59832_T15 (SEQ ID 768 771
NO: 104)
T59832_T22 (SEQ ID 510 513
NO: 105)
T59832_T28 (SEQ ID 1549 1552
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1927 1930
T59832_T8 (SEQ ID NO: 108) 1279 1282

Segment cluster T59832_node—36 (SEQ ID NO:134) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 837 845
NO: 103)
T59832_T15 (SEQ ID 772 780
NO: 104)
T59832_T22 (SEQ ID 514 522
NO: 105)
T59832_T28 (SEQ ID 1553 1561
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1931 1939
T59832_T8 (SEQ ID NO: 108) 1283 1291

Segment cluster T59832_node—37 (SEQ ID NO:135) according to the present invention is supported by 300 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 846 945
NO: 103)
T59832_T15 (SEQ ID 781 880
NO: 104)
T59832_T22 (SEQ ID 523 622
NO: 105)
T59832_T28 (SEQ ID 1562 1661
NO: 106)
T59832_T6 (SEQ ID NO: 107) 1940 2039
T59832_T8 (SEQ ID NO: 108) 1292 1391

Segment cluster T59832_node—38 (SEQ ID NO:136) according to the present invention is supported by 247 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T28 (SEQ ID NO:106), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 946 1030
NO: 103)
T59832_T15 (SEQ ID 881 965
NO: 104)
T59832_T22 (SEQ ID 623 707
NO: 105)
T59832_T28 (SEQ ID 1662 1746
NO: 106)
T59832_T6 (SEQ ID NO: 107) 2040 2124
T59832_T8 (SEQ ID NO: 108) 1392 1476

Segment cluster T59832_node—4 (SEQ ID NO:137) according to the present invention is supported by 296 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 173 223
NO: 103)
T59832_T15 (SEQ ID 173 223
NO: 104)
T59832_T22 (SEQ ID 173 223
NO: 105)
T59832_T6 (SEQ ID NO: 107) 173 223
T59832_T8 (SEQ ID NO: 108) 173 223

Segment cluster T59832_node—5 (SEQ ID NO:138) according to the present invention is supported by 305 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 224 259
NO: 103)
T59832_T15 (SEQ ID 224 259
NO: 104)
T59832_T22 (SEQ ID 224 259
NO: 105)
T59832_T6 (SEQ ID NO: 107) 224 259
T59832_T8 (SEQ ID NO: 108) 224 259

Segment cluster T59832_node—6 (SEQ ID NO:139) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T22 (SEQ ID NO:105), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 260 280
NO: 103)
T59832_T15 (SEQ ID 260 280
NO: 104)
T59832_T22 (SEQ ID 260 280
NO: 105)
T59832_T6 (SEQ ID NO: 107) 260 280
T59832_T8 (SEQ ID NO: 108) 260 280

Segment cluster T59832_node—8 (SEQ ID NO:140) according to the present invention can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 281 301
NO: 103)
T59832_T15 (SEQ ID 281 301
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1347 1367
T59832_T8 (SEQ ID NO: 108) 281 301

Segment cluster T59832_node—9 (SEQ ID NO:141) according to the present invention is supported by 330 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T59832_T11 (SEQ ID NO:103), T59832_T15 (SEQ ID NO:104), T59832_T6 (SEQ ID NO:107) and T59832_T8 (SEQ ID NO:108). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T59832_T11 (SEQ ID 302 337
NO: 103)
T59832_T15 (SEQ ID 302 337
NO: 104)
T59832_T6 (SEQ ID NO: 107) 1368 1403
T59832_T8 (SEQ ID NO: 108) 302 337

Variant protein alignment to the previously known protein:

Sequence name: /tmp/YQPBtaxsLQ/JxSZR3ZR2p:GILT_HUMAN (SEQ ID NO:142)

Sequence documentation:

Alignment of: T59832_P5 (SEQ ID NO:143)×GILT_HUMAN (SEQ ID NO:142).

Alignment segment 1/1:

Quality: 429.00
Escore: 0
Matching length: 46 Total length: 46
Matching Percent 97.83 Matching Percent Identity: 97.83
Similarity:
Total Percent Similarity: 97.83 Total Percent Identity: 97.83
Gaps: 0

Alignment:

         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKVG 46
|||||||||||||||||||||||||||||||||||||||||||| |
12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTG 57

Sequence name: /tmp/9HrQ57oZG0/ugNVzp0l7X:GILT_HUMAN (SEQ ID NO:142)

Sequence documentation:

Alignment of: T59832_P7 (SEQ ID NO:144)×GILT_HUMAN (SEQ ID NO:142).

Alignment segment 1/1:

Quality: 2110.00
Escore: 0
Matching length: 212 Total length: 212
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
||||||||||||||||||||||||||||||||||||||||||||||||||
112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161
         .         .         .         .         .
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
||||||||||||||||||||||||||||||||||||||||||||||||||
162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211
         .
201 PHEYVPWVTVNG 212
||||||||||||
212 PHEYVPWVTVNG 223

Sequence name: /tmp/9HrQ57oZG0/ugNVzp0l7X:BAC98466 (SEQ ID NO:848)

Sequence documentation:

Alignment of: T59832_P7 (SEQ ID NO:144)×BAC98466 (SEQ ID NO:848).

Alignment segment 1/1:

Quality: 2110.00
Escore: 0
Matching length: 212 Total length: 212
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
         .
201 PHEYVPWVTVNG 212
||||||||||||
201 PHEYVPWVTVNG 212

Sequence name: /tmp/9HrQ57oZG0/ugNVzp0l7X:BAC85622 (SEQ ID NO:849)

Sequence documentation:

Alignment of: T59832_P7 (SEQ ID NO:144)×BAC85622 (SEQ ID NO:849).

Alignment segment 1/1:

Quality: 1496.00
Escore: 0
Matching length: 148 Total length: 148
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
91 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 140
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 50
         .         .         .         .         .
141 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 190
||||||||||||||||||||||||||||||||||||||||||||||||||
51 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 100
         .         .         .         .
191 NAQRTDALQPPHEYVPWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR 238
||||||||||||||||||||||||||||||||||||||||||||||||
101 NAQRTDALQPPHEYVPWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR 148

Sequence name: /tmp/9HrQ57oZG0/ugNVzp0l7X:Q8WU77 (SEQ ID NO:850)

Sequence documentation:

Alignment of: T59832_P7 (SEQ ID NO:144)×Q8WU77 (SEQ ID NO:850).

Alignment segment 1/1:

Quality: 2110.00
Escore: 0
Matching length: 212 Total length: 212
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
         .
201 PHEYVPWVTVNG 212
||||||||||||
201 PHEYVPWVTVNG 212

Sequence name: /tmp/lttCiW30od/feIXLDs4rU:GILT_HUMAN (SEQ ID NO:142)

Sequence documentation:

Alignment of: T59832_P9 (SEQ ID NO:145)×GILT_HUMAN (SEQ ID NO:142).

Alignment segment 1/1:

Quality: 2016.00
Escore: 0
Matching length: 203 Total length: 203
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDEFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
||||||||||||||||||||||||||||||||||||||||||||||||||
112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161
         .         .         .         .         .
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
||||||||||||||||||||||||||||||||||||||||||||||||||
162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211
201 PHE 203
|||
212 PHE 214

Sequence name: /tmp/lttCiW30od/feIXLDs4rU:BAC98466 (SEQ ID NO:848)

Sequence documentation:

Alignment of: T59832_P9 (SEQ ID NO:145)×BAC98466 (SEQ ID NO:848).

Alignment segment 1/1:

Quality: 2016.00
Escore: 0
Matching length: 203 Total length: 203
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
201 PHE 203
|||
201 PHE 203

Sequence name: /tmp/lttCiW30od/feIXLDs4rU:BAC85622 (SEQ ID NO:849)

Sequence documentation:

Alignment of: T59832_P9 (SEQ ID NO:145)×BAC85622 (SEQ ID NO:849).

Alignment segment 1/1:

Quality: 1145.00
Escore: 0
Matching length: 113 Total length: 113
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
91 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKENKVEACVLDELDME 140
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 50
         .         .         .         .         .
141 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 190
||||||||||||||||||||||||||||||||||||||||||||||||||
51 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 100
         .
191 NAQRTDALQPPHE 203
|||||||||||||
101 NAQRTDALQPPHE 113

Sequence name: /tmp/lttCiW30od/feIXLDs4rU:Q8WU77 (SEQ ID NO:850)

Sequence documentation:

Alignment of: T59832_P9 (SEQ ID NO:145)×Q8WU77 (SEQ ID NO:850).

Alignment segment 1/1:

Quality: 2016.00
Escore: 0
Matching length: 203 Total length: 203
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
201 PHE 203
|||
201 PHE 203

Sequence name: /tmp/sIHTwdduiK/ToMKmEJiZc:GILT_HUMAN (SEQ ID NO:142)

Sequence documentation:

Alignment of: T59832_P12 (SEQ ID NO:146)×GILT_HUMAN (SEQ ID NO:142).

Alignment segment 1/1:

Quality: 2084.00
Escore: 0
Matching length: 219 Total length: 250
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 87.60 Total Percent Identity: 87.60
Gaps: 1

Alignment:

1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVE.................... 130
||||||||||||||||||||||||||||||
112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161
         .         .         .         .         .
131 ...........CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 169
           |||||||||||||||||||||||||||||||||||||||
162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211
         .         .         .         .         .
170 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 219
||||||||||||||||||||||||||||||||||||||||||||||||||
212 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 261

Sequence name: /tmp/sIHTwdduiK/ToMKmEJiZc:BAC85622 (SEQ ID NO:849)

Sequence documentation:

Alignment of: T59832_P12 (SEQ ID NO:146)×BAC85622 (SEQ ID NO:849).

Alignment segment 1/1:

Quality: 835.00
Escore: 0
Matching length: 91 Total length: 122
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 74.59 Total Percent Identity: 74.59
Gaps: 1

Alignment:

         .         .         .         .         .
91 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE.......... 130
||||||||||||||||||||||||||||||||||||||||
1 MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDME 50
         .         .         .         .         .
131 .....................CLQLYAPGLSPDTIMECAMGDRGMQLMHA 159
                     |||||||||||||||||||||||||||||
51 LAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHA 100
         .         .
160 NAQRTDALQPPHEYVPWVTVNG 181
||||||||||||||||||||||
101 NAQRTDALQPPHEYVPWVTVNG 122

Sequence name: /tmp/sIHTwdduiK/ToMKmEJiZc:Q8WU77 (SEQ ID NO:850)

Sequence documentation:

Alignment of: T59832_P12 (SEQ ID NO:146)×Q8WU77 (SEQ ID NO:850).

Alignment segment 1/1:

Quality: 2084.00
Escore: 0
Matching length: 219 Total length: 250
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 87.60 Total Percent Identity: 87.60
Gaps: 1

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVE.................... 130
||||||||||||||||||||||||||||||
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
131 ...........CLQLYAPGLSPDTIMECAMGDRCMQLMHANAQRTDALQP 169
           |||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
         .         .         .         .         .
170 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 219
||||||||||||||||||||||||||||||||||||||||||||||||||
201 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 250

Sequence name: /tmp/LH4xf8J65f/a95JQoTfNB:GILT_HUMAN (SEQ ID NO:142)

Sequence documentation:

Alignment of: T59832_P18 (SEQ ID NO:147)×GILT_HUMAN (SEQ ID NO:142).

Alignment segment 1/1:

Quality: 1222.00
Escore: 0
Matching length: 133 Total length: 250
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 53.20 Total Percent Identity: 53.20
Gaps: 1

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK...... 44
||||||||||||||||||||||||||||||||||||||||||||
12 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 61
         .         .         .         .         .
44 .................................................. 44
62 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 111
         .         .         .         .         .
44 .................................................. 44
112 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 161
         .         .         .         .         .
45 ...........CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 83
           |||||||||||||||||||||||||||||||||||||||
162 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 211
         .         .         .         .         .
84 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 133
||||||||||||||||||||||||||||||||||||||||||||||||||
212 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 261

Sequence name: /tmp/LH4xf8J65f/a95JQoTfNB:Q8WU77 (SEQ ID NO:850)

Sequence documentation:

Alignment of: T59832_P18 (SEQ ID NO:147)×Q8WU77 (SEQ ID NO:850).

Alignment segment 1/1:

Quality: 1222.00
Escore: 0
Matching length: 133 Total length: 250
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 53.20 Total Percent Identity: 53.20
Gaps: 1

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK...... 44
||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
44 .................................................. 44
51 RGPLKKSNAPLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
44 .................................................. 44
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
45 ...........CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 83
           |||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
         .         .         .         .         .
84 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 133
||||||||||||||||||||||||||||||||||||||||||||||||||
201 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 250

Sequence name: /tmp/LH4xf8J65f/a95JQoTfNB:Q8NEI4 (SEQ ID NO:851)

Sequence documentation:

Alignment of: T59832_P18 (SEQ ID NO:147)×Q8NEI4 (SEQ ID NO:851).

Alignment segment 1/1:

Quality: 1222.00
Escore: 0
Matching length: 133 Total length: 250
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 53.20 Total Percent Identity: 53.20
Gaps: 1

Alignment:

         .         .         .         .         .
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK...... 44
||||||||||||||||||||||||||||||||||||||||||||
1 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYL 50
         .         .         .         .         .
44 .................................................. 44
51 RGPLKKSNAPLVNVTLYYEALCGGCQAFLIRELFPTWLLVMEILNVTLVP 100
         .         .         .         .         .
44 .................................................. 44
101 YGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVCME 150
         .         .         .         .         .
45 ...........CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 83
           |||||||||||||||||||||||||||||||||||||||
151 EFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQP 200
         .         .         .         .         .
84 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 133
||||||||||||||||||||||||||||||||||||||||||||||||||
201 PHEYVPWVTVNGKPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK 250

Expression of Gamma-Interferon Inducible Lysosomal Thiol Reductase (GILT) T59832 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T59832junc6-25-26 (SEQ ID NO:854) in Normal and Cancerous Breast Tissues

Expression of gamma-interferon inducible lysosomal thiol reductase (GILT) transcripts detectable by or according to junc6-25-26, T59832junc6-25-26 (SEQ ID NO:854) amplicon and primers T59832junc6-25-26F (SEQ ID NO:852) T59832junc6-25-26R (SEQ ID NO:853) was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO :925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1 above, “Tissue samples in testing panel”, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 18 is a histogram showing over expression of the above-indicated gamma-interferon inducible lysosomal thiol reductase (GILT) transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 18, the expression of gamma-interferon inducible lysosomal thiol reductase (GILT) transcripts detectable by the above amplicon(s) in cancer samples was higher in a few samples than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1 above, “Tissue samples in testing panel”). Notably an over-expression of at least 7 fold was found in 3 out of 28 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T59832junc6-25-26F forward primer (SEQ ID NO:852); and T59832junc6-25-26R reverse primer (SEQ ID NO:853).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T59832junc6-25-26 (SEQ ID NO:854).

Forward primer T59832junc6-25-26F: (SEQ ID NO: 852)
CCACCAGTTAACTACAAGTGCCTG
Reverse primer T59832junc6-25-26R: (SEQ ID NO: 853)
GCGTGCATGAGCTGCATG
Amplicon T59832junc6-25-26: (SEQ ID NO: 854)
CCACCAGTTAACTACAAGTGCCTGCAGCTCTACGCCCCAGGGCTGTCGCCAGACAC
TATCATGGAGTGTGCAATGGGGGACCGCGGCATGCAGCTCATGCACGC

Description for Cluster HUMGRP5E

Cluster HUMGRP5E features 2 transcript(s) and 5 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HUMGRP5E_T4 148
HUMGRP5E_T5 149

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HUMGRP5E_node_0 150
HUMGRP5E_node_2 151
HUMGRP5E_node_8 152
HUMGRP5E_node_3 153
HUMGRP5E_node_7 154

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
HUMGRP5E_P4 156
HUMGRP5E_P5 157

These sequences are variants of the known protein Gastrin-releasing peptide precursor (SEQ ID NO: 155) (SwissProt accession identifier GRP_HUMAN; known also according to the synonyms GRP; GRP-10), SEQ ID NO: 155, referred to herein as the previously known protein.

Gastrin-releasing peptide is known or believed to have the following function(s): stimulates gastrin release as well as other gastrointestinal hormones. The sequence for protein Gastrin-releasing peptide precursor (SEQ ID NO:155) is given at the end of the application, as “Gastrin-releasing peptide precursor (SEQ ID NO:155) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
4 S -> R

Protein Gastrin-releasing peptide localization is believed to be Secreted.

The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Diabetes, Type II. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Bombesin antagonist; Insulinotropin agonist. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anorectic/Antiobesity; Releasing hormone; Anticancer; Respiratory; Antidiabetic.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: signal transduction; neuropeptide signaling pathway, which are annotation(s) related to Biological Process; growth factor, which are annotation(s) related to Molecular Function; and secreted, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

As noted above, cluster HUMGRP5E features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Gastrin-releasing peptide precursor (SEQ ID NO:155). A description of each variant protein according to the present invention is now provided.

Variant protein HUMGRP5E_P4 (SEQ ID NO:156) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGRP5E_T4 (SEQ ID NO:148). An alignment is given to the known protein (Gastrin-releasing peptide precursor (SEQ ID NO:155) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMGRP5E_P4 (SEQ ID NO:156) and GRP_HUMAN (SEQ ID NO:155):

1.An isolated chimeric polypeptide encoding for HUMGRP5E_P4 (SEQ ID NO:156), comprising a first amino acid sequence being at least 90% homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1-127 of GRP_HUMAN (SEQ ID NO:155), which also corresponds to amino acids 1-127 of HUMGRP5E_P4 (SEQ ID NO:156), and a second amino acid sequence being at least 90% homologous to GSQREGRNPQLNQQ corresponding to amino acids 135-148 of GRP_HUMAN (SEQ ID NO:155), which also corresponds to amino acids 128-141 of HUMGRP5E_P4 (SEQ ID NO:156), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2.An isolated chimeric polypeptide encoding for an edge portion of HUMGRP5E_P4 (SEQ ID NO:156), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KG, having a structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino acid numbers 128+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMGRP5E_P4 (SEQ ID NO:156) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5E_P4 (SEQ ID NO:156) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 S -> R Yes

Variant protein HUMGRP5E_P4 (SEQ ID NO:156) is encoded by the following transcript(s): HUMGRP5E_T4 (SEQ ID NO:148), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGRP5E_T4 (SEQ ID NO:148) is shown in bold; this coding portion starts at position 622 and ends at position 1044. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5E_P4 (SEQ ID NO:156) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
541 -> T No
542 G -> T No
631 A -> C Yes
672 G -> A Yes
1340 C -> No
1340 C -> A No
1341 A -> No
1341 A -> G No

Variant protein HUMGRP5E_P5 (SEQ ID NO:157) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGRP5E_T5 (SEQ ID NO:149). An alignment is given to the known protein (Gastrin-releasing peptide precursor (SEQ ID NO:155) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMGRP5E_P5 (SEQ ID NO:157) and GRP_HUMAN (SEQ ID NO:155):

1. An isolated chimeric polypeptide encoding for HUMGRP5E_P5 (SEQ ID NO:157), comprising a first amino acid sequence being at least 90% homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1-127 of GRP_HUMAN (SEQ ID NO:155), which also corresponds to amino acids 1-127 of HUMGRP5E_P5 (SEQ ID NO:157), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DSLLQVLNVKEGTPS (SEQ ID NO:1017) corresponding to amino acids 128-142 of HUMGRP5E_P5 (SEQ ID NO:157), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMGRP5E_P5 (SEQ ID NO:157), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DSLLQVLNVKEGTPS (SEQ ID NO:1017) in HUMGRP5E_P5 (SEQ ID NO:157).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMGRP5E_P5 (SEQ ID NO:157) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5E_P5 (SEQ ID NO:157) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 S -> R Yes

Variant protein HUMGRP5E_P5 (SEQ ID NO:157) is encoded by the following transcript(s): HUMGRP5E_T5 (SEQ ID NO:149), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGRP5E_T5 (SEQ ID NO:149) is shown in bold; this coding portion starts at position 622 and ends at position 1047. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGRP5E_P5 (SEQ ID NO:157) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
541 -> T No
542 G -> T No
631 A -> C Yes
672 G -> A Yes
1354 C -> No
1354 C -> A No
1355 A -> No
1355 A -> G No

As noted above, cluster HUMGRP5E features 5 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMGRP5E_node—0 (SEQ ID NO:150) according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGRP5E_T4 (SEQ ID NO:148) and HUMGRP5E_T5 (SEQ ID NO:149). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
HUMGRP5E_T4 1 760
(SEQ ID NO: 148)
HUMGRP5E_T5 1 760
(SEQ ID NO: 149)

Segment cluster HUMGRP5E_node—2 (SEQ ID NO:151) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGRP5E_T4 (SEQ ID NO:148) and HUMGRP5E_T5 (SEQ ID NO:149). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
HUMGRP5E_T4 761 984
(SEQ ID NO: 148)
HUMGRP5E_T5 761 984
(SEQ ID NO: 149)

Segment cluster HUMGRP5E_node—8 (SEQ ID NO:152) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGRP5E_T4 (SEQ ID NO:148) and HUMGRP5E_T5 (SEQ ID NO:149). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
HUMGRP5E_T4 1004 1362
(SEQ ID NO: 148)
HUMGRP5E_T5 1018 1376
(SEQ ID NO: 149)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HUMGRP5E_node—3 (SEQ ID NO:153) according to the present invention can be found in the following transcript(s): HUMGRP5E_T4 (SEQ ID NO:148) and HUMGRP5E_T5 (SEQ ID NO:149). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
HUMGRP5E_T4 985 1003
(SEQ ID NO: 148)
HUMGRP5E_T5 985 1003
(SEQ ID NO: 149)

Segment cluster HUMGRP5E_node—7 (SEQ ID NO:154) according to the present invention can be found in the following transcript(s): HUMGRP5E_T5 (SEQ ID NO:149). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segement Segment
Transcript name starting position ending position
HUMGRP5E_T5 1004 1017
(SEQ ID NO:149)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/412zs2mwyT/B0wjOUAX0d:GRP_HUMAN (SEQ ID NO:155)

Sequence documentation:

Alignment of: HUMGRP5E_P4 (SEQ ID NO:156)×GRP_HUMAN (SEQ ID NO:155).

Alignment segment 1/1:

Quality: 1291.00
Escore: 0
Matching length: 141 Total length: 148
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 95.27 Total Percent Identity: 95.27
Gaps: 1

Alignment:

         .         .         .         .         .
1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50
         .         .         .         .         .
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100
         .         .         .         .
101 PKALGNQQPSWDSEDSSNFKDVGSKGK.......GSQREGRNPQLNQQ 141
|||||||||||||||||||||||||||       ||||||||||||||
101 PKALGNQQPSWDSEDSSNFKDVGSKGKVGRLSAPGSQREGRNPQLNQQ 148

Sequence name: /tmp/1me9ldnvfv/KbP5io8PtU:GRP_HUMAN (SEQ ID NO:155)

Sequence documentation:

Alignment of: HUMGRP5E_P5 (SEQ ID NO:157)×GRP HUMAN (SEQ ID NO:155).

Alignment segment 1/1:

Quality: 1248.00
Escore: 0
Matching length: 127 Total length: 127
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLM 50
         .         .         .         .         .
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 GKKSTGESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQ 100
         .         .
101 PKALGNQQPSWDSEDSSNFKDVGSKGK 127
|||||||||||||||||||||||||||
101 PKALGNQQPSWDSEDSSNFKDVGSKGK 127

Expression of GRP_HUMAN-Gastrin-Releasing Peptide(HUMGRP5E) Transcripts, Which are Detectable by Amplicon, as Depicted in Sequence Name HUMGRP5Ejunc3-7 (SEQ ID NO:857) in Normal and Cancerous Breast Tissues

Expression of GRP_HUMAN-gastrin-releasing peptide transcripts detectable by or according to junc3-7, HUMGRP5Ejunc3-7 (SEQ ID NO:857) amplicon(s) and HUMGRP5Ejunc3-7F (SEQ ID NO:855) and HUMGRP5Ejunc3-7R (SEQ ID NO:856) primers was measured by real time PCR. In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), and SDHA (GenBank Accession No. NM—004168. (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925 ), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67 Table 1, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 19 is a histogram showing over expression of the above-indicated GRP_HUMAN-gastrin-releasing peptide transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.

As is evident from FIG. 19, the expression of GRP_HUMAN-gastrin-releasing peptide transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1 “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 12 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of GRP_HUMAN-gastrin-releasing peptide transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 7.22E-04.

Threshold of 5 fold over expression was found to differentiate between cancer and normal samples with P value of 1.12E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMGRP5Ejunc3-7F forward primer (SEQ ID NO:855); and HUMGRP5Ejunc3-7R reverse primer (SEQ ID NO:856).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:

HUMGRP5Ejunc3-7. (SEQ ID NO:857)
HUMGRP5Ejunc3-7F (SEQ ID NO:855)
ACCAGCCACCTCAACCCA
HUMGRP5Ejunc3-7R (SEQ ID NO:856)
CTGGAGCAGAGAGTCTTTGCCT
HUMGRP5Ejunc3-7 (SEQ ID NO:857)
ACCAGCCACCTCAACCCAAGGCCCTGGGCAATCAGCAGCCTTCGTGGGAT
TCAGAGGATAGCAGCAACTTCAAAGATGTAGGTTCAAAAGGCAAAGACTC
TCTGCTCCAG

Expression of GRP_HUMAN-Gastrin-Releasing Peptide (HUMGRP5E) Transcripts, Which are Detectable by Amplicon, as Depicted in Sequence Name HUMGRP5Ejunc3-7 (SEQ ID NO:857) in Different Normal Tissues

Expression of GRP_HUMAN-gastrin-releasing peptide transcripts detectable by or according to HUMGRP5E junc3-7 amplicon(s) and HUMGRP5E junc3-7F and HUMGRP5E junc3-7R was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937 ), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos. 33-35 above, Table 2, “Tissue samples in normal panel”), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above.

The results are presented in FIG. 20, demonstrating the expression of GRP_HUMAN—gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7 (SEQ ID NO:857), in different normal tissues.

Description for Cluster AA155578

Cluster AA155578 features 4 transcript(s) and 15 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
AA155578_PEA_1_T10 158
AA155578_PEA_1_T12 159
AA155578_PEA_1_T13 160
AA155578_PEA_1_T8 161

TABLE 2
Segments of interest
Segment Name Sequence ID No.
AA155578_PEA_1_node_11 162
AA155578_PEA_1_node_12 163
AA155578_PEA_1_node_14 164
AA155578_PEA_1_node_19 165
AA155578_PEA_1_node_21 166
AA155578_PEA_1_node_23 167
AA155578_PEA_1_node_24 168
AA155578_PEA_1_node_25 169
AA155578_PEA_1_node_4 170
AA155578_PEA_1_node_7 171
AA155578_PEA_1_node_15 172
AA155578_PEA_1_node_18 173
AA155578_PEA_1_node_22 174
AA155578_PEA_1_node_6 175
AA155578_PEA_1_node_8 176

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
AA155578_PEA_1_P4 178
AA155578_PEA_1_P6 179
AA155578_PEA_1_P8 180
AA155578_PEA_1_P9 181

These sequences are variants of the known protein Kallikrein 10 precursor (SEQ ID NO:177) (SwissProt accession identifier KLKA_HUMAN; known also according to the synonyms EC 3.4.21.-; Protease serine-like 1; Normal epithelial cell-specific 1), SEQ ID NO: 177, referred to herein as the previously known protein.

Protein Kallikrein 10 precursor (SEQ ID NO:177) is known or believed to have the following function(s): Has a tumor-suppressor role for NES1 in breast and prostate cancer. The sequence for protein Kallikrein 10 precursor (SEQ ID NO:177) is given at the end of the application, as “Kallikrein 10 precursor (SEQ ID NO:177) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
50 A -> S
149 P -> L

Protein Kallikrein 10 precursor (SEQ ID NO:177) localization is believed to be Secreted (Probable).

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: proteolysis and peptidolysis, which are annotation(s) related to Biological Process; chymotrypsin; trypsin; serine-type peptidase; hydrolase, which are annotation(s) related to Molecular Function; and extracellular, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster AA155578 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 21 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 21 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

TABLE 5
Normal tissue distribution
Name of Tissue Number
Brain 0
Colon 0
epithelial 17
general 5
head and neck 0
Lung 14
Ovary 0
pancreas 0
prostate 4
Skin 80
stomach 0
Uterus 45

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
Brain 1 3.7e−01 1 1.0 3.5e−02 5.1
Colon 6.3e−02 2.9e−02 2.4e−01 2.9 1.6e−01 3.2
epithelial 4.9e−03 2.0e−02 7.5e−04 2.1 2.3e−03 1.9
general 7.8e−07 7.2e−06 3.8e−10 4.8 2.6e−10 4.4
head and neck 1.0e−02 3.5e−02 4.6e−01 2.5 7.5e−01 1.4
Lung 8.5e−01 9.2e−01 1 0.5 1 0.5
Ovary 2.2e−01 1.6e−01 1.0e−02 3.3 1.8e−02 3.4
pancreas 3.3e−01 6.9e−02 3.2e−02 3.7 2.4e−04 10.0
prostate 8.3e−01 8.7e−01 6.7e−01 1.2 7.5e−01 1.1
Skin 6.0e−01 8.1e−01 3.2e−01 1.9 1 0.3
stomach 3.0e−01 2.7e−01 2.5e−01 3.0 1.6e−01 2.3
Uterus 1.8e−01 3.2e−01 5.6e−01 0.8 6.8e−01 0.8

As noted above, cluster AA155578 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Kallikrein 10 precursor (SEQ ID NO:177). A description of each variant protein according to the present invention is now provided.

Variant protein AA155578_PEA—1_P4 (SEQ ID NO:178) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA155578_PEA—1_T10 (SEQ ID NO:158). An alignment is given to the known protein (Kallikrein 10 precursor (SEQ ID NO:177) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between AA155578_PEA—1_P4 (SEQ ID NO:178) and KLKA_HUMAN (SEQ ID NO:177):

1. An isolated chimeric polypeptide encoding for AA155578_PEA—1_P4 (SEQ ID NO:178), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDHLLLLQGEQLRRTT RSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP corresponding to amino acids 1-146 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-146 of AA155578_PEA—1_P4 (SEQ ID NO:178), and a second amino acid sequence being at least 90% homologous to YNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGIL SWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 184-276 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 147-239 of AA155578_PEA—1_P4 (SEQ ID NO:178), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA—1_P4 (SEQ ID NO:178), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PY, having a structure as follows: a sequence starting from any of amino acid numbers 146-x to 146; and ending at any of amino acid numbers 147+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein AA155578_PEA—1_P4 (SEQ ID NO:178) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P4 (SEQ ID NO:178) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
123 Q -> R No
145 R -> G No
145 R -> M Yes
168 Y -> No
19 K -> No
194 G -> No
43 L -> S No
50 A -> S Yes
60 Q -> R No

Variant protein AA155578_PEA—1_P4 (SEQ ID NO:178) is encoded by the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA—1_T10 SEQ ID NO:158) is shown in bold; this coding portion starts at position 148 and ends at position 864. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P4 (SEQ ID NO:178) sequence provides support for the deduced sequence variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
19 C -> G Yes
88 G -> No
570 A -> G Yes
580 A -> G No
581 G -> T Yes
651 C -> No
729 C -> No
733 C -> T No
875 G -> A No
906 C -> A No
907 C -> A No
952 C -> A No
204 G -> No
953 C -> A No
994 C -> A Yes
1125 C -> T Yes
1192 C -> T Yes
1330 G -> No
1330 G -> T Yes
275 T -> C No
295 G -> T Yes
326 A -> G No
444 C -> T Yes
465 C -> A Yes
483 G -> C Yes
515 A -> G No

Variant protein AA155578_PEA—1_P6 (SEQ ID NO:179) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA155578_PEA—1_T12 (SEQ ID NO:159). An alignment is given to the known protein (Kallikrein 10 precursor (SEQ ID NO:177) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between AA155578_PEA—1_P6 (SEQ ID NO:179) and KLKA_HUMAN (SEQ ID NO:177):

1. An isolated chimeric polypeptide encoding for AA155578_PEA—1_P6 (SEQ ID NO:179), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1-29 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-29 of AA155578_PEA—1_P6 (SEQ ID NO:179), and a second amino acid sequence being at least 90% homologous to VKYNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQ GILSWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 182-276 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 30-124 of AA155578_PEA—1_P6 (SEQ ID NO:179), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA—1_P6 (SEQ ID NO:179), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise WV, having a structure as follows: a sequence starting from any of amino acid numbers 29-x to 29; and ending at any of amino acid numbers 30+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein AA155578_PEA—1_P6 (SEQ ID NO:179) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P6 (SEQ ID NO:179) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
19 K -> No
53 Y -> No
79 G -> No

Variant protein AA155578_PEA—1_P6 (SEQ ID NO:179) is encoded by the following transcript(s): AA155578_PEA—1_T12 (SEQ ID NO:159), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA—1_T12 (SEQ ID NO:159) is shown in bold; this coding portion starts at position 148 and ends at position 519. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P6 (SEQ ID NO:179) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
19 C -> G Yes
88 G -> No
608 C -> A No
649 C -> A Yes
780 C -> T Yes
847 C -> T Yes
985 G -> No
985 G -> T Yes
204 G -> No
306 C -> No
384 C -> No
388 C -> T No
530 G -> A No
561 C -> A No
562 C -> A No
607 C -> A No

Variant protein AA155578_PEA—1_P8 (SEQ ID NO:180) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA155578_PEA—1_T8 (SEQ ID NO:161). An alignment is given to the known protein (Kallikrein 10 precursor (SEQ ID NO:177) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between AA155578_PEA—1_P8 (SEQ ID NO:180) and KLKA_HUMAN (SEQ ID NO:177):

1. An isolated chimeric polypeptide encoding for AA155578_PEA—1_P8 (SEQ ID NO:180), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1-29 of KLKA_HUMAN (SEQ ID NO:177 , which also corresponds to amino acids 1-29 of AA155578_PEA—1_P8 (SEQ ID NO:180), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GHCGLE (SEQ ID NO:1018) corresponding to amino acids 30-35 of AA155578_PEA—1_P8 (SEQ ID NO:180), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of AA155578_PEA—1_P8 (SEQ ID NO:180), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GHCGLE (SEQ ID NO:1018) in AA155578_PEA—1_P8 (SEQ ID NO:180).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein AA155578_PEA—1_P8 (SEQ ID NO:180) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P8 (SEQ ID NO:180) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
19 K -> No

Variant protein AA155578_PEA—1_P8 (SEQ ID NO:180) is encoded by the following transcript(s): AA155578_PEA—1_T8 (SEQ ID NO:161), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA—1_T8 (SEQ ID NO:161) is shown in bold; this coding portion starts at position 285 and ends at position 389. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P8 (SEQ ID NO:180) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
341 G -> No
400 C -> T Yes
718 C -> No
796 C -> No
800 C -> T No
942 G -> A No
973 C -> A No
974 C -> A No
1019 C -> A No
1020 C -> A No
1061 C -> A Yes
1192 C -> T Yes
421 C -> A Yes
1259 C -> T Yes
1397 G -> No
1397 G -> T Yes
439 G -> C Yes
471 A -> G No
526 A -> G Yes
536 A -> G No
537 G -> T Yes
549 C -> T Yes
587 T -> C No

Variant protein AA155578_PEA—1_P9 (SEQ ID NO:181) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA155578_PEA—1_T13 (SEQ ID NO:160). An alignment is given to the known protein (Kallikrein 10 precursor (SEQ ID NO:177)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between AA155578_PEA—1_P9 (SEQ ID NO:181) and KLKA_HUMAN (SEQ ID NO:177):

1. An isolated chimeric polypeptide encoding for AA155578_PEA—1_P9 (SEQ ID NO:181), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK corresponding to amino acids 1-90 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-90 of AA155578_PEA—1_P9 (SEQ ID NO:181).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein AA155578_PEA—1_P9 (SEQ ID NO:181) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P9 (SEQ ID NO:181) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
19 K -> No
43 L -> S No
50 A -> S Yes
60 Q -> R No

Variant protein AA155578_PEA—1_P9 (SEQ ID NO:181) is encoded by the following transcript(s): AA155578_PEA—1_T13 (SEQ ID NO:160), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA155578_PEA—1_T13 (SEQ ID NO:160) is shown in bold; this coding portion starts at position 148 and ends at position 417. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA155578_PEA—1_P9 (SEQ ID NO:181) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
19 C -> G Yes
88 G -> No
204 G -> No
275 T -> C No
295 G -> T Yes
326 A -> G No
559 G -> C Yes
560 C -> G Yes
582 A -> G Yes
919 T -> A Yes

As noted above, cluster AA155578 features 15 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster AA155578_PEA—1_node—11 (SEQ ID NO:162) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158) and AA155578_PEA—1_T13 (SEQ ID NO:160). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
AA155578_PEA_1_T10 236 416
(SEQ ID NO: 158)
AA155578_PEA_1_T13 236 416
(SEQ ID NO: 160)

Segment cluster AA155578_PEA—1_node—12 (SEQ ID NO:163) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T13 (SEQ ID NO:160). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
AA155578_PEA_1_T13 417 935
(SEQ ID NO: 160)

Segment cluster AA155578_PEA—1_node—14 (SEQ ID NO:164) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 417 585
(SEQ ID NO: 158)
AA155578_PEA_1_T8 373 541
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—19 (SEQ ID NO:165) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 586 714
(SEQ ID NO: 158)
AA155578_PEA_1_T12 241 369
(SEQ ID NO: 159)
AA155578_PEA_1_T8 653 781
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—21 (SEQ ID NO:166) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 715 863
(SEQ ID NO: 158)
AA155578_PEA_1_T12 370 518
(SEQ ID NO: 159)
AA155578_PEA_1_T8 782 930
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—23 (SEQ ID NO:167) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 887 1063
(SEQ ID NO: 158)
AA155578_PEA_1_T12 542 718
(SEQ ID NO: 159)
AA155578_PEA_1_T8 954 1130
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—24 (SEQ ID NO:168) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 1064 1184
(SEQ ID NO: 158)
AA155578_PEA_1_T12 719 839
(SEQ ID NO: 159)
AA155578_PEA_1_T8 1131 1251
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—25 (SEQ ID NO:169) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 1185 1397
(SEQ ID NO: 158)
AA155578_PEA_1_T12 840 1052
(SEQ ID NO: 159)
AA155578_PEA_1_T8 1252 1464
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—4 (SEQ ID NO:170) according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T13 (SEQ ID NO:160). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 1 138
(SEQ ID NO: 158)
AA155578_PEA_1_T12 1 138
(SEQ ID NO: 159)
AA155578_PEA_1_T13 1 138
(SEQ ID NO: 160)

Segment cluster AA155578_PEA—1_node—7 (SEQ ID NO:171) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T8 (SEQ ID NO:161). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T8 92 275
(SEQ ID NO: 161)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster AA155578_PEA—1_node—15 (SEQ ID NO:172) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T8 (SEQ ID NO:161). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T8 542 647
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—18 (SEQ ID NO:173) according to the present invention can be found in the following transcript(s): AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T12 236 240
(SEQ ID NO: 159)
AA155578_PEA_1_T8 648 652
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—22 (SEQ ID NO:174) according to the present invention can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 864 886
(SEQ ID NO: 158)
AA155578_PEA_1_T12 519 541
(SEQ ID NO: 159)
AA155578_PEA_1_T8 931 953
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—6 (SEQ ID NO:175) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T8 (SEQ ID NO:161). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T8 1 91
(SEQ ID NO: 161)

Segment cluster AA155578_PEA—1_node—8 (SEQ ID NO:176) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA155578_PEA—1_T10 (SEQ ID NO:158), AA155578_PEA—1_T12 (SEQ ID NO:159), AA155578_PEA—1_T13 (SEQ ID NO:160) and AA155578_PEA—1_T8 (SEQ ID NO:161). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AA155578_PEA_1_T10 139 235
(SEQ ID NO: 158)
AA155578_PEA_1_T12 139 235
(SEQ ID NO: 159)
AA155578_PEA_1_T13 139 235
(SEQ ID NO: 160)
AA155578_PEA_1_T8 276 372
(SEQ ID NO: 161)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/4gXdRV0C1z/cQ4LqHmh5A:KLKA_HUMAN (SEQ ID NO:177)

Sequence documentation:

Alignment of: AA155578_PEA—1_P4 (SEQ ID NO:178)×KLKA_HUMAN (SEQ ID NO:177).

Alignment segment 1/1:

Quality: 2283.00
Escore: 0
Matching length: 239 Total length: 276
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 86.59 Total Percent Identity: 86.59
Gaps: 1

Alignment:

         .         .         .         .         .
1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50
         .         .         .         .         .
51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDH 100
         .         .         .         .         .
101 LLLLQGEQLRRTTRSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP.... 146
||||||||||||||||||||||||||||||||||||||||||||||
101 LLLLQGEQLRRTTRSVVHPKYHQGSGPILPRRTDEHDLMLLKLARPVVPG 150
         .         .         .         .         .
147 .................................YNKGLTCSSITILSPKE 163
                                 |||||||||||||||||
151 PRVRALQLPYRCAQPGDQCQVAGWGTTAARRVKYNKGLTCSSITILSPKE 200
         .         .         .         .         .
164 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 213
||||||||||||||||||||||||||||||||||||||||||||||||||
201 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 250
         .         .
214 GSAQHPAVYTQICKYMSWINKVIRSN 239
||||||||||||||||||||||||||
251 GSAQHPAVYTQICKYMSWINKVIRSN 276

Sequence name: /tmp/3VxcRS97HN/X9ncdxjYQx:KLKA_HUMAN (SEQ ID NO:177)

Sequence documentation:

Alignment of: AA155578_PEA—1_P6 (SEQ ID NO:179)×KLKA_HUMAN (SEQ ID NO:177).

Alignment segment 1/1:

Quality: 1140.00
Escore: 0
Matching length: 124 Total length: 276
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 44.93 Total Percent Identity: 44.93
Gaps: 1

Alignment:

         .         .         .         .         .
1 MRAPHLHLSAASGARALAKLLPLLMAQLW..................... 29
|||||||||||||||||||||||||||||
1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50
         .         .         .         .         .
29 .................................................. 29
51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDH 100
         .         .         .         .         .
29 .................................................. 29
101 LLLLQGEQLRRTTRSVVHPKYHQGSGPILPRRTDEHDLMLLKLARPVVPG 150
         .         .         .         .         .
30 ...............................VKYNKGLTCSSITILSPKE 48
                               |||||||||||||||||||
151 PRVRALQLPYRCAQPGDQCQVAGWGTTAARRVKYNKGLTCSSITILSPKE 200
         .         .         .         .         .
49 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 98
||||||||||||||||||||||||||||||||||||||||||||||||||
201 CEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGILSWGVYPC 250
         .         .
99 GSAQHPAVYTQICKYMSWINKVIRSN 124
||||||||||||||||||||||||||
251 GSAQHPAVYTQICKYMSWINKVIRSN 276

Sequence name: /tmp/LsSdTeu0qX/6luiCMKTi9:KLKA_HUMAN (SEQ ID NO:177)

Sequence documentation:

Alignment of: AA155578_PEA—1_P8 (SEQ ID NO:180)×KLKA_HUMAN (SEQ ID NO:177).

Alignment segment 1/1:

Quality: 279.00
Escore: 0
Matching length: 29 Total length: 29
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .
1 MRAPHLHLSAASGARALAKLLPLLMAQLW 29
|||||||||||||||||||||||||||||
1 MRAPHLHLSAASGARALAKLLPLLMAQLW 29

Sequence name: /tmp/kcfKGMcF7s/YnKnMy8D1q:KLKA_HUMAN (SEQ ID NO:177)

Sequence documentation:

Alignment of: AA155578_PEA—1_P9 (SEQ ID NO:181)×KLKA_HUMAN (SEQ ID NO:177)

Alignment segment 1/1:

Quality: 887.00
Escore: 0
Matching length: 90 Total length: 90
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGA 50
         .         .         .         .
51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK 90
||||||||||||||||||||||||||||||||||||||||
51 PCARGSQPWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK 90

Description for Cluster HSENA78

Cluster HSENA78 features 1 transcript(s) and 7 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HSENA78_T5 182

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HSENA78_node_0 183
HSENA78_node_2 184
HSENA78_node_6 185
HSENA78_node_9 186
HSENA78_node_3 187
HSENA78_node_4 188
HSENA78_node_8 189

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
HSENA78_P2 191

These sequences are variants of the known protein Small inducible cytokine B5 precursor (SEQ ID NO:190) (SwissProt accession identifier SZ05_HUMAN; known also according to the synonyms CXCL5; Epithelial-derived neutrophil activating protein 78; Neutrophil-activating peptide ENA-78), SEQ ID NO: 190, referred to herein as the previously known protein.

Protein Small inducible cytokine B5 precursor (SEQ ID NO:190) is known or believed to have the following function(s): Involved in neutrophil activation. The sequence for protein Small inducible cytokine B5 precursor (SEQ ID NO:190) is given at the end of the application, as “Small inducible cytokine B5 precursor (SEQ ID NO:190) amino acid sequence”. Protein Small inducible cytokine B5 precursor (SEQ ID NO:190) localization is believed to be Secreted.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: chemotaxis; signal transduction; cell-cell signaling; positive control of cell proliferation, which are annotation(s) related to Biological Process; and chemokine, which are annotation(s) related to Molecular Function.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HSENA78 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 22 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 22 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and lung malignant tumors.

TABLE 4
Normal tissue distribution
Name of Tissue Number
Colon 0
epithelial 2
general 38
kidney 0
Lung 3
Breast 8
Skin 0
stomach 36
Uterus 4

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
colon 2.6e−01 3.3e−01 1.7e−01 2.7 2.7e−01 2.2
epithelial 2.5e−01 9.0e−02 3.2e−03 4.1 8.5e−07 5.5
general 8.4e−01 7.2e−01 1 0.3 1 0.4
kidney 1 7.2e−01 1 1.0 1.7e−01 1.9
lung 8.5e−01 4.8e−01 4.1e−01 1.9 4.0e−05 3.8
breast 9.5e−01 8.7e−01 1 0.8 6.8e−01 1.2
skin 2.9e−01 4.7e−01 1.4e−01 7.0 6.4e−01 1.6
stomach 5.0e−01 4.3e−01 7.5e−01 1.0 4.3e−01 1.3
uterus 7.1e−01 8.5e−01 6.6e−01 1.3 8.0e−01 1.0

As noted above, cluster HSENA78 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Small inducible cytokine B5 precursor (SEQ ID NO:190). A description of each variant protein according to the present invention is now provided.

Variant protein HSENA78_P2 (SEQ ID NO:191) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSENA78_T5 (SEQ ID NO:182). An alignment is given to the known protein (Small inducible cytokine B5 precursor (SEQ ID NO:190)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSENA78_P2 (SEQ ID NO:191) and SZ05_HUMAN (SEQ ID NO:190):

1. An isolated chimeric polypeptide encoding for HSENA78_P2 (SEQ ID NO:191), comprising a first amino acid sequence being at least 90% homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHP KMISNLQVFAIGPQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN (SEQ ID NO:190), which also corresponds to amino acids 1-81 of HSENA78_P2 (SEQ ID NO:191).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSENA78_P2 (SEQ ID NO:191) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSENA78_P2 (SEQ ID NO:191) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Amino acid mutations
SNP position(s) on Alternative Previously known
amino acid sequence amino acid(s) SNP?
80 V -> No
81 V -> No

Variant protein HSENA78_P2 (SEQ ID NO:191) is encoded by the following transcript(s): HSENA78_T5 (SEQ ID NO:182), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSENA78_T5 (SEQ ID NO:182) is shown in bold; this coding portion starts at position 149 and ends at position 391. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSENA78_P2 (SEQ ID NO:191) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
92 C -> T Yes
144 C -> T No
1151 A -> T Yes
1389 T -> C No
1867 C -> G Yes
145 C -> T No
181 C -> T Yes
316 G -> A Yes
388 G -> No
390 T -> No
605 T -> No
972 C -> T Yes
1105 A -> G Yes

As noted above, cluster HSENA78 features 7 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSENA78_node—0 (SEQ ID NO:183) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 1 257
(SEQ ID NO:182)

Segment cluster HSENA78_node—2 (SEQ ID NO:184) according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 258 390
(SEQ ID NO:182)

Segment cluster HSENA78_node—6 (SEQ ID NO:185) according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 585 2370
(SEQ ID NO:182)

Segment cluster HSENA78_node—9 (SEQ ID NO:186) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 2394 2546
(SEQ ID NO:182)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HSENA78_node—3 (SEQ ID NO:187) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 391 500
(SEQ ID NO:182)

Segment cluster HSENA78_node—4 (SEQ ID NO:188) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 501 584
(SEQ ID NO:182)

Segment cluster HSENA78_node—8 (SEQ ID NO:189) according to the present invention can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:182). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSENA78_T5 2371 2393
(SEQ ID NO:182)

Microarray (chip) data is also available for this gene as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 15.

TABLE 15
Oligonucleotides related to this gene
Overexpressed
Oligonucleotide name in cancers Chip reference
HSENA78_0_1_0 breast cancer Breast
(SEQ ID NO:898)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/5kiQY6MxWx/pLnTrxsCqk:SZ05_HUMAN (SEQ ID NO:190)

Sequence documentation:

Alignment of: HSENA78_P2 (SEQ ID NO:191)×SZ05_HUMAN (SEQ ID NO:190).

Alignment segment 1/1:

Quality: 767.00
Escore: 0
Matching length: 81 Total length: 81
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCV 50
         .         .         .
51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81
|||||||||||||||||||||||||||||||
51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81

Description for Cluster T94936

Cluster T94936 features 2 transcript(s) and 12 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
T94936_PEA_1_T1 192
T94936_PEA_1_T2 193

TABLE 2
Segments of interest
Segment Name Sequence ID No.
T94936_PEA_1_node_14 194
T94936_PEA_1_node_16 195
T94936_PEA_1_node_2 196
T94936_PEA_1_node_20 197
T94936_PEA_1_node_23 198
T94936_PEA_1_node_0 199
T94936_PEA_1_node_11 200
T94936_PEA_1_node_13 201
T94936_PEA_1_node_17 202
T94936_PEA_1_node_6 203
T94936_PEA_1_node_8 204
T94936_PEA_1_node_9 205

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
T94936_PEA_1_P2 206
T94936_PEA_1_P3 207

As noted above, cluster T94936 features 2 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein T94936_PEA—1_P2 (SEQ ID NO:206) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T94936_PEA—1_T1 (SEQ ID NO:192). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T94936_PEA—1_P2 (SEQ ID NO:206) and Q8TD06 (SEQ ID NO:858) (SEQ ID NO:858):

1. An isolated chimeric polypeptide encoding for T94936_PEA—1_P2 (SEQ ID NO:206), comprising a first amino acid sequence being at least 90% homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL corresponding to amino acids 1-150 of Q8TD06 (SEQ ID NO:858), which also corresponds to amino acids 1-150 of T94936_PEA—1_P2 (SEQ ID NO:206).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T94936_PEA—1_P2 (SEQ ID NO:206) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 4, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA—1_P2 (SEQ ID NO:206) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 4
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
104 T -> A No
28 K -> R No

Variant protein T94936_PEA—1_P2 (SEQ ID NO:206) is encoded by the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T94936_PEA—1_T1 (SEQ ID NO:192) is shown in bold; this coding portion starts at position 76 and ends at position 525. The transcript also has the following SNPs as listed in Table 5 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA—1_P2 (SEQ ID NO:206) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
158 A -> G No
186 A -> G No
385 A -> G No

Variant protein T94936_PEA—1_P3 (SEQ ID NO:207) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T94936_PEA—1_T2 (SEQ ID NO:193). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T94936_PEA—1_P3 (SEQ ID NO:207) and Q8TD06 (SEQ ID NO:858):

1. An isolated chimeric polypeptide encoding for T94936_PEA—1_P3 (SEQ ID NO:207), comprising a first amino acid sequence being at least 90% homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFV corresponding to amino acids 1-122 of Q8TD06 (SEQ ID NO:858), which also corresponds to amino acids 1-122 of T94936_PEA—1_P3 (SEQ ID NO:207), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMYVISFHQIYKISRNQHSCFYF (SEQ ID NO: 1019) corresponding to amino acids 123-145 of T94936_PEA—1_P3 (SEQ ID NO:207), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T94936_PEA—1_P3 (SEQ ID NO:207), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMYVISFHQIYKISRNQHSCFYF (SEQ ID NO:1019) in T94936_PEA—1_P3 (SEQ ID NO:207).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T94936_PEA—1_P3 (SEQ ID NO:207) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA—1_P3 (SEQ ID NO:207) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
104 T -> A No
28 K -> R No

Variant protein T94936_PEA—1_P3 (SEQ ID NO:207) is encoded by the following transcript(s): T94936_PEA—1_T2 (SEQ ID NO:193), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T94936_PEA—1_T2 (SEQ ID NO:193) is shown in bold; this coding portion starts at position 76 and ends at position 510. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T94936_PEA—1_P3 (SEQ ID NO:207) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
158 A -> G No
186 A -> G No
385 A -> G No
746 T -> C No
889 A -> C No
889 A -> G No
980 A -> No
1006 A -> No
1105 A -> No
1356 A -> G No

As noted above, cluster T94936 features 12 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T94936_PEA—1_node—14 (SEQ ID NO:194) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T2 (SEQ ID NO:193). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T2 (SEQ ID 443 803
NO: 193)

Segment cluster T94936_PEA—1_node—16 (SEQ ID NO:195) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T2 (SEQ ID NO:193). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T2 (SEQ ID 804 1213
NO: 193)

Segment cluster T94936_PEA—1_node—2 (SEQ ID NO:196) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 49 184
NO: 192)
T94936_PEA_1_T2 (SEQ ID 49 184
NO: 193)

Segment cluster T94936_PEA—1_node—20 (SEQ ID NO:197) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T2 (SEQ ID NO:193). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T2 (SEQ ID 1298 1526
NO: 193)

Segment cluster T94936_PEA—1_node—23 (SEQ ID NO:198) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 527 751
NO: 192)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster T94936_PEA—1_node—0 (SEQ ID NO:199) according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 1 48
NO: 192)
T94936_PEA_1_T2 (SEQ ID 1 48
NO: 193)

Segment cluster T94936_PEA—1_node—11 (SEQ ID NO:200) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 302 378
NO: 192)
T94936_PEA_1_T2 (SEQ ID 302 378
NO: 193)

Segment cluster T94936_PEA—1_node—13 (SEQ ID NO:201) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 379 442
NO: 192)
T94936_PEA_1_T2 (SEQ ID 379 442
NO: 193)

Segment cluster T94936_PEA—1_node—17 (SEQ ID NO:202) according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 443 526
NO: 192)
T94936_PEA_1_T2 (SEQ ID 1214 1297
NO: 193)

Segment cluster T94936_PEA —1node—6 (SEQ ID NO:203) according to the present invention is supported by 74 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 185 248
NO: 192)
T94936_PEA_1_T2 (SEQ ID 185 248
NO: 193)

Segment cluster T94936_PEA—1_node—8 (SEQ ID NO:204) according to the present invention can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO:192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 249 252
NO: 192)
T94936_PEA_1_T2 (SEQ ID 249 252
NO: 193)

Segment cluster T94936_PEA—1_node—9 (SEQ ID NO:205) according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T94936_PEA—1_T1 (SEQ ID NO: 192) and T94936_PEA—1_T2 (SEQ ID NO:193). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T94936_PEA_1_T1 (SEQ ID 253 301
NO: 192)
T94936_PEA_1_T2 (SEQ ID 253 301
NO: 193)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/1R8BEXWutz/cdFRKHIcZR:Q8TD06 (SEQ ID NO:858).

Sequence documentation:

Alignment of: T94936_PEA—1_P2 (SEQ ID NO:206)×Q8TD06 (SEQ ID NO:858).

Alignment segment 1/1:

Quality: 1486.00
Escore: 0
Matching length: 150 Total length: 150
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50
         .         .         .         .         .
51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100
         .         .         .         .         .
101 MHETTDKNLSPDGQYVPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 MHETTDKNLSPDGQYVPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL 150

Sequence name: /tmp/AG3unO0N3y/kjgGehygST:Q8TD06 (SEQ ID NO:858)

Sequence documentation:

Alignment of: T94936_PEA—1_P3 (SEQ ID NO:207)×Q8TD06 (SEQ ID NO:858).

Alignment segment 1/1:

Quality: 1214.00
Escore: 0
Matching length: 122 Total length: 122
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEE 50
         .         .         .         .         .
51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 GLFYAQKSKKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNL 100
         .         .
101 MHETTDKNLSPDGQYVPRIMFV 122
||||||||||||||||||||||
101 MHETTDKNLSPDGQYVPRIMFV 122

Expression of Homo sapiens Breast Cancer Membrane Protein 11 (BCMP11) T94936 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T94936 seg14 (SEQ ID NO:861) in Normal and Cancerous Breast Tissues

Expression of Homo sapiens breast cancer membrane protein 11 (BCMP11) transcripts detectable by or according to seg14, T94936 seg14 (SEQ ID NO:861) amplicon(s) and T94936 seg14F (SEQ ID NO:859) and T94936 seg14R (SEQ ID NO:860) primers was measured by real time PCR. In this specific example, the real-time PCR reaction efficiency was assumed to be 2 and was not calculated by a standard curve reaction (as detailed above in the section of “Real-Time RT-PCR analysis”). In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 23 is a histogram showing over expression of the above-indicated Homo sapiens breast cancer membrane protein 11 (BCMP11) transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 23, the expression of Homo sapiens breast cancer membrane protein 11 (BCMP11) transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1, above, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 17 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Homo sapiens breast cancer membrane protein 11 (BCMP11) transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 7.94E-02.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.74E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T94936 seg14F forward primer (SEQ ID NO:859); and T94936 seg14R reverse primer (SEQ ID NO:860).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T94936 seg14 (SEQ ID NO:861).

T94936 seg14 Forward primer: (SEQ ID NO:859)
TACAAAATTAGTAGAAATCAGCATTCTTGC
T94936 seg14 Reverse primer: (SEQ ID NO:860)
TGTAGAACTAACAAGAGCTGATATTATTGGAT
T94936 seg14 Amplicon: (SEQ ID NO:861)
TACAAAATTAGTAGAAATCAGCATTCTTGCTTTTATTTTTAAATGCTAGT
TCAAGTACTATTCTTTTTAAAGAGAAGTCATTTCTAATCCAATAATATCA
GCTCTTGTTAGTTCTACA

Description for Cluster Z41644

Cluster Z41644 features 1 transcript(s) and 21 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
Z41644_PEA_1_T5 208

TABLE 2
Segments of interest
Segment Name Sequence ID No.
Z41644_PEA_1_node_0 209
Z41644_PEA_1_node_11 210
Z41644_PEA_1_node_12 211
Z41644_PEA_1_node_15 212
Z41644_PEA_1_node_20 213
Z41644_PEA_1_node_24 214
Z41644_PEA_1_node_1 215
Z41644_PEA_1_node_10 216
Z41644_PEA_1_node_13 217
Z41644_PEA_1_node_16 218
Z41644_PEA_1_node_17 219
Z41644_PEA_1_node_19 220
Z41644_PEA_1_node_2 221
Z41644_PEA_1_node_21 222
Z41644_PEA_1_node_22 223
Z41644_PEA_1_node_23 224
Z41644_PEA_1_node_25 225
Z41644_PEA_1_node_3 226
Z41644_PEA_1_node_4 227
Z41644_PEA_1_node_6 228
Z41644_PEA_1_node_9 229

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
Z41644_PEA_1_P10 231

These sequences are variants of the known protein Small inducible cytokine B14 precursor (SEQ ID NO:230) (SwissProt accession identifier SZ14_HUMAN; known also according to the synonyms CXCL14; Chemokine BRAK), SEQ ID NO: 230, referred to herein as the previously known protein.

Protein Small inducible cytokine B14 precursor (SEQ ID NO:230) is known or believed to have the following function(s): Not chemotactive for T-cells, B-cells, monocytes, natural killer cells or ghranulocytes. Does not inhibit proliferation of myeloid progenitors in colony formation assays. The sequence for protein Small inducible cytokine B14 precursor (SEQ ID NO:230) is given at the end of the application, as “Small inducible cytokine B14 precursor (SEQ ID NO:230) amino acid sequence”. Protein Small inducible cytokine B14 precursor (SEQ ID NO:230) localization is believed to be Secreted.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: chemotaxis; signal transduction; cell-cell signaling, which are annotation(s) related to Biological Process; and chemokine, which are annotation(s) related to Molecular Function.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster Z41644 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 24 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 24 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: lung malignant tumors, breast malignant tumors and pancreas carcinoma.

TABLE 4
Normal tissue distribution
Name of Tissue Number
bone 45
brain 62
colon 327
epithelial 179
general 104
head and neck 10
kidney 219
lung 6
lymph nodes 37
breast 87
bone marrow 0
muscle 20
ovary 36
Pancreas 0
prostate 78
skin 591
stomach 109
Thyroid 386
uterus 218

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
bone 4.9e−01 8.5e−01 1.8e−01 1.9 5.3e−01 1.0
brain 6.7e−01 8.0e−01 9.1e−01 0.6 9.9e−01 0.4
colon 6.4e−01 7.7e−01 9.7e−01 0.4 1 0.3
epithelial 4.1e−01 9.4e−01 9.6e−01 0.7 1 0.4
general 1.5e−01 9.4e−01 1.8e−01 1.0 1 0.5
head and neck 1.9e−01 3.3e−01 4.6e−01 2.8 7.5e−01 1.5
kidney 7.7e−01 8.2e−01 7.0e−01 0.7 9.5e−01 0.5
lung 2.2e−01 5.0e−01 1.3e−04 8.7 8.1e−03 4.1
lymph nodes 6.3e−01 8.7e−01 6.3e−01 1.2 9.2e−01 0.6
breast 4.0e−01 6.5e−01 3.9e−04 3.5 2.9e−02 1.9
bone marrow 1 6.7e−01 1 1.0 5.3e−01 1.9
muscle 5.2e−01 6.1e−01 2.7e−01 3.2 6.3e−01 1.2
ovary 6.7e−01 7.1e−01 7.6e−01 1.0 8.6e−01 0.8
pancreas 2.2e−02 2.3e−02 5.7e−03 7.8 1.6e−03 8.2
prostate 8.8e−01 9.0e−01 8.3e−01 0.6 9.3e−01 0.5
skin 5.9e−01 6.9e−01 2.3e−01 0.3 1 0.0
stomach 6.1e−01 8.9e−01 8.1e−01 0.7 9.9e−01 0.4
Thyroid 7.0e−01 7.0e−01 9.9e−01 0.4 9.9e−01 0.4
uterus 5.3e−01 8.2e−01 9.5e−01 0.5 1 0.3

As noted above, cluster Z41644 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Small inducible cytokine B14 precursor (SEQ ID NO:230). A description of each variant protein according to the present invention is now provided.

Variant protein Z41644_PEA—1_P10 (SEQ ID NO:231) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z41644_PEA—1_T5 (SEQ ID NO:208). An alignment is given to the known protein (Small inducible cytokine B14 precursor (SEQ ID NO:230)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between Z41644_PEA—1_P10 (SEQ ID NO:231) and SZ14_HUMAN (SEQ ID NO:230):

1. An isolated chimeric polypeptide encoding for Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 1-95 of SZ14_HUMAN (SEQ ID NO:230), which also corresponds to amino acids 1-95 of Z41644_PEA—1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA—1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA—1_P10 (SEQ ID NO:231).

Comparison report between Z41644_PEA—1_P10 (SEQ ID NO:231) and Q9NS21 (SEQ ID NO:862):

1. An isolated chimeric polypeptide encoding for Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of Q9NS21 (SEQ ID NO:862), which also corresponds to amino acids 1-95 of Z41644_PEA—1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA—1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA—1_P10 (SEQ ID NO:231).

Comparison report between Z41644_PEA—1_P10 (SEQ ID NO:231) and AAQ89265 (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of AAQ89265, which also corresponds to amino acids 1-95 of Z41644_PEA—1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA—1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z41644_PEA—1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA—1_P10 (SEQ ID NO:231).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein Z41644_PEA—1_P10 (SEQ ID NO:231) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z41644_PEA—1_P10 (SEQ ID NO:231) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
32 P -> H Yes
64 S -> No
80 T -> A No
80 T -> P No

Variant protein Z41644_PEA—1_P10 (SEQ ID NO:231) is encoded by the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z41644_PEA—1_T5 (SEQ ID NO:208) is shown in bold; this coding portion starts at position 744 and ends at position 1112. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z41644_PEA—1_P10 (SEQ ID NO:231) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
102 A -> G Yes
572 C -> No
3707 C -> T Yes
3735 C -> T Yes
4079 G -> A No
4123 G -> A Yes
4233 A -> G Yes
4328 C -> No
4350 A -> G Yes
4376 G -> A Yes
4390 A -> G Yes
4619 G -> T Yes
838 C -> A Yes
4754 C -> T No
4757 C -> A No
4794 T -> G No
4827 G -> No
934 C -> No
981 A -> C No
981 A -> G No
1817 A -> C Yes
2546 T -> No
2684 T -> A No
2885 T -> C Yes

As noted above, cluster Z41644 features 21 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z41644_PEA—1_node—0 (SEQ ID NO:209) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 1 616
NO: 208)

Segment cluster Z41644_PEA—1_node—11 (SEQ ID NO:210) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 1028 2089
NO: 208)

Segment cluster Z41644_PEA—1_node—12 (SEQ ID NO:211) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 2090 2350
NO: 208)

Segment cluster Z41644_PEA—1_node—15 (SEQ ID NO:212) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 2368 3728
NO: 208)

Segment cluster Z41644_PEA—1_node—20 (SEQ ID NO:213) according to the present invention is supported by 260 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 3938 4506
NO: 208)

Segment cluster Z41644_PEA—1_node—24 (SEQ ID NO:214) according to the present invention is supported by 185 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 4637 4799
NO: 208)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster Z41644_PEA—1_node—1 (SEQ ID NO:215) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 617 697
NO: 208)

Segment cluster Z41644_PEA—1_node—10 (SEQ ID NO:216) according to the present invention is supported by 138 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 972 1027
NO: 208)

Segment cluster Z41644_PEA—1_node—13 (SEQ ID NO:217) according to the present invention can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 2351 2367
NO: 208)

Segment cluster Z41644_PEA—1_node—16 (SEQ ID NO:218) according to the present invention is supported by 152 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment ending
starting position
Transcript name position Segment
Z41644_PEA_1_T5 (SEQ ID 3729 3809
NO: 208)

Segment cluster Z41644_PEA—1_node—17 (SEQ ID NO:219) according to the present invention can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 3810 3829
NO: 208)

Segment cluster Z41644_PEA—1_node—19 (SEQ ID NO:220) according to the present invention is supported by 112 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 3830 3937
NO: 208)

Segment cluster Z41644_PEA—1_node—2 (SEQ ID NO:221) according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 698 737
NO: 208)

Segment cluster Z41644_PEA—1_node—21 (SEQ ID NO:222) according to the present invention can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 4507 4529
NO: 208)

Segment cluster Z41644_PEA—1_node—22 (SEQ ID NO:223) according to the present invention is supported by 164 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 4530 4582
NO: 208)

Segment cluster Z41644_PEA—1_node—23 (SEQ ID NO:224) according to the present invention is supported by 169 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 4583 4636
NO: 208)

Segment cluster Z41644_PEA—1_node—25 (SEQ ID NO:225) according to the present invention is supported by 138 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 4800 4902
NO: 208)

Segment cluster Z41644_PEA—1_node—3 (SEQ ID NO:226) according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 738 773
NO: 208)

Segment cluster Z41644_PEA—1_node—4 (SEQ ID NO:227) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 774 807
NO: 208)

Segment cluster Z41644_PEA—1_node—6 (SEQ ID NO:228) according to the present invention is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 808 913
NO: 208)

Segment cluster Z41644_PEA—1_node—9 (SEQ ID NO:229) according to the present invention is supported by 134 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z41644_PEA—1_T5 (SEQ ID NO:208). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 914 971
NO: 208)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:SZ14_HUMAN (SEQ ID NO:230)

Sequence documentation:

Alignment of: Z41644_PEA—1_P10 (SEQ ID NO:231)×SZ14_HUMAN (SEQ ID NO:230).

Alignment segment 1/1:

Quality: 953.00
Escore: 0
Matching length: 95 Total length: 95
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50
         .         .         .         .
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95
|||||||||||||||||||||||||||||||||||||||||||||
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95

Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:Q9NS21 (SEQ ID NO:862)

Sequence documentation:

Alignment of: Z41644_PEA—1_P10 (SEQ ID NO:231)×Q9NS21 (SEQ ID NO:862).

Alignment segment 1/1:

Quality: 957.00
Escore: 0
Matching length: 96 Total length: 96
Matching Percent 100.00 Matching Percent Identity: 98.96
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 98.96
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50
||||||||||||||||||||||||||||||||||||||||||||||||||
13 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 62
         .         .         .         .
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRRY 96
|||||||||||||||||||||||||||||||||||||||||||||:
63 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRRF 108

Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:AAQ89265

Sequence documentation:

Alignment of: Z41644_PEA—1_P10 (SEQ ID NO:231)×AAQ89265.

Alignment segment 1/1:

Quality: 953.00
Escore: 0
Matching length: 95 Total length: 95
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 50
||||||||||||||||||||||||||||||||||||||||||||||||||
13 MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPH 62
         .         .         .         .
51 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 95
|||||||||||||||||||||||||||||||||||||||||||||
63 CEEKMVIITTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR 107

Description for Cluster M85491

Cluster M85491 features 2 transcript(s) and 11 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
M85491_PEA_1_T16 232
M85491_PEA_1_T20 233

TABLE 2
Segments of interest
Segment Name Sequence ID No.
M85491_PEA_1_node_0 234
M85491_PEA_1_node_13 235
M85491_PEA_1_node_21 236
M85491_PEA_1_node_23 237
M85491_PEA_1_node_24 238
M85491_PEA_1_node_8 239
M85491_PEA_1_node_9 240
M85491_PEA_1_node_10 241
M85491_PEA_1_node_18 242
M85491_PEA_1_node_19 243
M85491_PEA_1_node_6 244

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
M85491_PEA_1_P13 246
M85491_PEA_1_P14 247

These sequences are variants of the known protein Ephrin type-B receptor 2 [precursor] (SEQ ID NO:245) (SwissProt accession identifier EPB2_HUMAN; known also according to the synonyms EC 2.7.1.112; Tyrosine-protein kinase receptor EPH-3; DRT; Receptor protein-tyrosine kinase HEK5; ERK), SEQ ID NO: 245, referred to herein as the previously known protein.

Protein Ephrin type-B receptor 2 [precursor] (SEQ ID NO:245) is known to have the following function(s): Receptor for members of the ephrin-B family. The sequence for protein Ephrin type-B receptor 2 [precursor] (SEQ ID NO:245) is given at the end of the application, as “Ephrin type-B receptor 2 [precursor] (SEQ ID NO:245) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNPposition(s) on
amino acid sequence Comment
671 A -> R./FTId = VAR_004162.
120 MALRRLGAALLLLPLLAAVE −>
MWVPVLALPVCTYA
923 E -> K
956 L -> V
958 V -> L
154 G -> D
476 K -> KQ
495-496 Missing
532 E -> D
568 R -> RR
589 M -> I
788 I -> F
853 S -> A

Protein Ephrin type-B receptor 2 [precursor] (SEQ ID NO:245) localization is believed to be Type I membrane protein.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein amino acid phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; neurogenesis, which are annotation(s) related to Biological Process; protein tyrosine kinase; receptor; transmembrane-ephrin receptor; ATP binding; transferase, which are annotation(s) related to Molecular Function; and integral membrane protein, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster M85491 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 25 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 25 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 5
Normal tissue distribution
Name of Tissue Number
Bladder 0
Bone 0
Brain 10
Colon 31
epithelial 10
general 12
Kidney 0
Liver 0
Lung 5
Breast 8
Muscle 5
Ovary 36
pancreas 10
Skin 0
stomach 0

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
bladder 5.4e−01 6.0e−01 3.2e−01 2.5 4.6e−01 1.9
Bone 1 2.8e−01 1 1.0 7.0e−01 1.8
Brain 3.4e−01 3.6e−01 1.2e−01 2.9 1.8e−02 2.7
Colon 3.4e−02 5.7e−02 8.2e−02 2.8 2.0e−01 2.1
epithelial 1.7e−03 3.5e−03 2.0e−03 2.8 1.1e−02 2.2
general 4.8e−04 5.2e−04 6.7e−04 2.3 1.3e−03 1.9
Kidney 4.3e−01 3.7e−01 1 1.1 7.0e−01 1.5
Liver 1 4.5e−01 1 1.0 6.9e−01 1.5
Lung 2.2e−01 2.7e−01 6.9e−02 3.6 3.4e−02 3.6
Breast 8.2e−01 7.3e−01 6.9e−01 1.2 6.8e−01 1.2
Muscle 9.2e−01 4.8e−01 1 0.8 1.5e−01 3.2
Ovary 8.5e−01 7.3e−01 9.0e−01 0.7 6.7e−01 1.0
pancreas 5.5e−01 2.0e−01 6.7e−01 1.2 3.5e−01 1.8
Skin 2.9e−01 4.7e−01 1.4e−01 7.0 6.4e−01 1.6
stomach 1.5e−01 3.2e−01 1 1.0 8.0e−01 1.3

As noted above, cluster M85491 features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ephrin type-B receptor 2 [precursor]. A description of each variant protein according to the present invention is now provided.

Variant protein M85491_PEA—1_P13 (SEQ ID NO:246) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M85491_PEA—1_T16 (SEQ ID NO:232). An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M85491_PEA—1_P13 (SEQ ID NO:246) and EPB2_HUMAN (SEQ ID NO:245):

1. An isolated chimeric polypeptide encoding for M8549 1_PEA—1_P13 (SEQ ID NO:246), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN SRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSG GREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAV NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL QYYEK corresponding to amino acids 1-476 of EPB2_HUMAN (SEQ ID NO:245), which also corresponds to amino acids 1-476 of M85491_PEA—1_P13 (SEQ ID NO:246), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:964) corresponding to amino acids 477-496 of M85491_PEA—1_P13 (SEQ ID NO:246), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M85491_PEA—1_P 13 (SEQ ID NO:246), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:964) in M85491_PEA—1_P13 (SEQ ID NO:246).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein M85491_PEA—1_P13 (SEQ ID NO:246) is encoded by the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA—1_T16 (SEQ ID NO:232) is shown in bold; this coding portion starts at position 143 and ends at position 1630. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA—1_P13 (SEQ ID NO:246) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
799 G -> A Yes
1066 C -> T Yes
1519 A -> G Yes
1872 C -> T Yes
2044 T -> C Yes
2156 G -> A Yes
2606 C -> A Yes
2637 G -> C Yes

Variant protein M85491_PEA—1_P14 (SEQ ID NO:247) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M85491_PEA—1_T20 (SEQ ID NO:233). An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M85491_PEA—1_P14 (SEQ ID NO:247) and EPB2_HUMAN (SEQ ID NO:245):

1. An isolated chimeric polypeptide encoding for M85491_PEA—1_P14 (SEQ ID NO:247), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:245), which also corresponds to amino acids 1-270 of M85491_PEA—1_P14 (SEQ ID NO:247), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:965) corresponding to amino acids 271-301 of M85491_PEA—1_P14 (SEQ ID NO:247), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M85491_PEA—1_P14 (SEQ ID NO:247), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:965) in M85491_PEA—1_P14 (SEQ ID NO:247).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M85491_PEA—1_P14 (SEQ ID NO:247) is encoded by the following transcript(s): M85491_PEA—1_T20 (SEQ ID NO:233), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA—1_T20 (SEQ ID NO:233) is shown in bold; this coding portion starts at position 143 and ends at position 1045. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA—1_P14 (SEQ ID NO:247) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
799 G -> A Yes
1135 T -> C Yes
1160 T -> C Yes
1172 A -> C Yes
1176 T -> A Yes

As noted above, cluster M85491 features 11 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster M85491_PEA—1_node—0 (SEQ ID NO:234) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232) and M85491_PEA—1_T20 (SEQ ID NO:233). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 1 203
ID NO: 232)
M85491_PEA_1_T20 (SEQ 1 203
ID NO: 233)

Segment cluster M85491_PEA—1_node—13 (SEQ ID NO:235) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T20 (SEQ ID NO:233). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T20 (SEQ 954 1182
ID NO: 233)

Segment cluster M85491_PEA—1_node—21 (SEQ ID NO:236) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 1110 1445
ID NO: 232)

Segment cluster M85491_PEA—1_node—23 (SEQ ID NO:237) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 1446 1570
ID NO: 232)

Segment cluster M85491_PEA—1_node—24 (SEQ ID NO:238) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 1571 2875
ID NO: 232)

Segment cluster M85491_PEA—1_node—8 (SEQ ID NO:239) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232) and M85491_PEA—1_T20 (SEQ ID NO:233). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 269 672
ID NO: 232)
M85491_PEA_1_T20 (SEQ 269 672
ID NO: 233)

Segment cluster M85491_PEA—1_node—9 (SEQ ID NO:240) according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232) and M85491_PEA—1_T20 (SEQ ID NO:233). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 673 856
ID NO: 232)
M85491_PEA_1_T20 (SEQ 673 856
ID NO: 233)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster M85491_PEA—1_node—10 (SEQ ID NO:241) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232) and M85491_PEA—1_T20 (SEQ ID NO:233). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 857 953
ID NO: 232)
M85491_PEA_1_T20 (SEQ 857 953
ID NO: 233)

Segment cluster M85491_PEA—1_node—18 (SEQ ID NO:242) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 954 1044
ID NO: 232)

Segment cluster M85491_PEA—1_node—19 (SEQ ID NO:243) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 1045 1109
ID NO: 232)

Segment cluster M85491_PEA—1_node—6 (SEQ ID NO:244) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA—1_T16 (SEQ ID NO:232) and M85491_PEA—1_T20 (SEQ ID NO:233). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M85491_PEA_1_T16 (SEQ 204 268
ID NO: 232)
M85491_PEA_1_T20 (SEQ 204 268
ID NO: 233)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/qfmsU9VtxS/DylcLC9j8v:EPB2_HUMAN (SEQ ID NO:245)

Sequence documentation:

Alignment of: M85491_PEA—1_P13 (SEQ ID NO:246)×EPB2_HUMAN (SEQ ID NO:245).

Alignment segment 1/1:

Quality: 4726.00
Escore: 0
Matching length: 476 Total length: 476
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
         .         .         .         .         .
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
         .         .         .         .         .
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
         .         .         .         .         .
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
         .         .         .         .         .
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
         .         .         .         .         .
251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300
         .         .         .         .         .
301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS 350
         .         .         .         .         .
351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400
         .         .         .         .         .
401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450
         .         .
451 SITLSWSQPDQPNGVILDYELQYYEK 476
||||||||||||||||||||||||||
451 SITLSWSQPDQPNGVILDYELQYYEK 476

Sequence name: /tmp/rmnzuDbot6/GiHbjeU8iR:EPB2_HUMAN (SEQ ID NO:245)

Sequence documentation:

Alignment of: M85491_PEA—1_P14 (SEQ ID NO:247)×EPB2_HUMAN (SEQ ID NO:245).

Alignment segment 1/1:

Quality: 2673.00
Escore: 0
Matching length: 270 Total length: 270
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50
         .         .         .         .         .
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
         .         .         .         .         .
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150
         .         .         .         .         .
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200
         .         .         .         .         .
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250
         .         .
251 IGRCMCKAGFEAVENGTVCR 270
||||||||||||||||||||
251 IGRCMCKAGFEAVENGTVCR 270

Expression of Ephrin Type-B Receptor 2 Precursor (EC 2.7.1.112) (Tyrosine-Protein Kinase Receptor EPH-3) M85491 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name M85491seg24 (SEQ ID NO:866) in Normal and Cancerous Breast Tissues

Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by or according to seg24, M85491seg24 (SEQ ID NO:866) amplicon and M85491seg24F (SEQ ID NO:864) M85491seg24R (SEQ ID NO:8656) primers was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 26 is a histogram showing over expression of the above-indicated Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 26, the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by the above amplicon in a few cancer samples was higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1, above, “Tissue samples in testing panel”).

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: M85491seg24F (SEQ ID NO:864) forward primer; and M85491seg24R (SEQ ID NO:865) reverse primer.

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: M85491 seg24 (SEQ ID NO:866).

M85491seg24 Forward primer (SEQ ID NO:864):
GGCGTCTTTCTCCCTCTGAAC
M85491seg24 Reverse primer (SEQ ID NO:865):
GTCCCATTCTGGGTGCTGTG
M85491seg24 Amplicon (SEQ ID NO:866):
GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGT
GAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGC
ACCCAGAATGGGAC

Expression of Ephrin Type-B Receptor 2 Precursor M85491 Transcripts, Which are Detectable by Amplicon as Depicted in Sequence Name M85491 seg24 (SEQ ID NO:866) in Different Normal Tissues

Expression of Ephrin type-B receptor 2 precursor transcripts detectable by or according to M85491 seg24 amplicon(s) (SEQ ID NO:866) and M85491 seg24F (SEQ ID NO:864) and M85491 seg24R (SEQ ID NO:865) priemrs was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL 19 (GenBank Accession No. NM—000981 (SEQ ID NO:934) RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the colon samples (Sample Nos. 1-3 Table 2,“Tissue samples on normal panel”, above), to obtain a value of relative expression of each sample relative to median of the colon samples. Primers and amplicon are as above.

The results are presented in FIG. 27, demonstrating the expression of Ephrin type-B receptor 2 precursor M85491 transcripts, which are detectable by amplicon as depicted in sequence name M85491 seg24 (SEQ ID NO:866), in different normal tissues.

Description for Cluster HSSTROL3

Cluster HSSTROL3 features 6 transcript(s) and 16 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HSSTROL3_T5 248
HSSTROL3_T8 249
HSSTROL3_T9 250
HSSTROL3_T10 251
HSSTROL3_T11 252
HSSTROL3_T12 253

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HSSTROL3_node_6 254
HSSTROL3_node_10 255
HSSTROL3_node_13 256
HSSTROL3_node_15 257
HSSTROL3_node_19 258
HSSTROL3_node_21 259
HSSTROL3_node_24 260
HSSTROL3_node_25 261
HSSTROL3_node_26 262
HSSTROL3_node_28 263
HSSTROL3_node_29 264
HSSTROL3_node_11 265
HSSTROL3_node_17 266
HSSTROL3_node_18 267
HSSTROL3_node_20 268
HSSTROL3_node_27 269

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
HSSTROL3_P4 271 HSSTROL3_T5
(SEQ ID NO:248)
HSSTROL3_P5 272 HSSTROL3_T8
(SEQ ID NO:249);
HSSTROL3_T9
(SEQ ID NO:250)
HSSTROL3_P7 273 HSSTROL3_T10
(SEQ ID NO:251)
HSSTROL3_P8 274 HSSTROL3_T11
(SEQ ID NO:252)
HSSTROL3_P9 275 HSSTROL3_T12
(SEQ ID NO:253)

These sequences are variants of the known protein Stromelysin-3 precursor (SEQ ID NO:270) (SwissProt accession identifier MM11_HUMAN; known also according to the synonyms EC 3.4.24.-; Matrix metalloproteinase-11; MMP-11; ST3; SL-3), SEQ ID NO: 270, referred to herein as the previously known protein.

Protein Stromelysin-3 precursor (SEQ ID NO:270) is known or believed to have the following function(s): May play an important role in the progression of epithelial malignancies. The sequence for protein Stromelysin-3 precursor (SEQ ID NO:270) is given at the end of the application, as “Stromelysin-3 precursor (SEQ ID NO:270) amino acid sequence”.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: proteolysis and peptidolysis; developmental processes; morphogenesis, which are annotation(s) related to Biological Process; stromelysin 3; calcium binding; zinc binding; hydrolase, which are annotation(s) related to Molecular Function; and extracellular matrix, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HSSTROL3 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 28 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 28 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

TABLE 4
Normal tissue distribution
Name of Tissue Number
Adrenal 0
Bladder 0
Brain 1
Colon 63
Epithelial 33
General 13
head and neck 101
Kidney 0
lung 11
breast 8
ovary 14
pancreas 0
prostate 2
skin 99
Thyroid 0
uterus 181

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 1 4.6e−01 1 1.0 5.3e−01 1.9
bladder 2.7e−01 3.4e−01 3.3e−03 4.9 2.1e−02 3.3
brain 3.5e−01 2.6e−01 1 1.7 3.3e−01 2.8
colon 7.7e−02 1.5e−01 3.1e−01 1.4 5.2e−01 1.0
epithelial 1.2e−04 1.2e−02 1.3e−06 2.7 4.6e−02 1.4
general 5.4e−09 3.1e−05 1.8e−16 5.0 3.1e−07 2.6
head and neck 4.6e−01 4.3e−01 1 0.6 9.4e−01 0.7
kidney 2.5e−01 3.5e−01 1.1e−01 4.0 2.4e−01 2.8
lung 1.8e−01 4.5e−01 1.9e−01 2.7 5.1e−01 1.4
breast 2.0e−01 3.4e−01 7.3e−02 3.3 2.5e−01 2.0
ovary 2.6e−01 3.2e−01 2.2e−02 2.0 7.0e−02 1.6
pancreas 9.5e−02 1.8e−01 1.8e−04 7.8 1.6e−03 5.5
prostate 8.2e−01 7.8e−01 4.5e−01 1.8 5.6e−01 1.5
skin 5.2e−01 5.8e−01 7.1e−01 0.8 1 0.3
Thyroid 2.9e−01 2.9e−01 1 1.1 1 1.1
uterus 4.2e−01 8.0e−01 7.5e−01 0.6 9.9e−01 0.4

As noted above, cluster HSSTROL3 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Stromelysin-3 precursor (SEQ ID NO:270). A description of each variant protein according to the present invention is now provided.

Variant protein HSSTROL3_P4 (SEQ ID NO:271) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T5 (SEQ ID NO:248). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:270)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSSTROL3_P4 (SEQ ID NO:271) and MM11_HUMAN (SEQ ID NO:270):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P4 (SEQ ID NO:271), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P4 (SEQ ID NO:271), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4 (SEQ ID NO:271), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPE KNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG corresponding to amino acids 165-445 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-445 of HSSTROL3_P4 (SEQ ID NO:271), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:966) corresponding to amino acids 446-496 of HSSTROL3_P4 (SEQ ID NO:271), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P4 (SEQ ID NO:271), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO:966)
ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVA
G
in
(SEQ ID NO:271)
HSSTROL3_P4.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSSTROL3_P4 (SEQ ID NO:271) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P4 (SEQ ID NO:271) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Amino acid mutations
SNP position(s) on amino Previously known
acid sequence Alternative amino acid(s) SNP?
38 V -> A Yes
104 R -> P Yes
214 A -> No
323 Q -> H Yes

Variant protein HSSTROL3_P4 (SEQ ID NO:271) is encoded by the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T5 (SEQ ID NO:248) is shown in bold; this coding portion starts at position 24 and ends at position 1511. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P4 (SEQ ID NO:271) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on nucleotide Previously known
sequence Alternative nucleic acid SNP?
136 T -> C Yes
334 G -> C Yes
663 G -> No
699 -> T No
992 G -> C Yes
1528 A -> G Yes
1710 A -> G Yes
2251 A -> G Yes
2392 C -> No
2444 C -> A Yes
2470 A -> T Yes
2687 -> G No
2696 -> G No
2710 C -> No
2729 -> A No
2755 T -> C No
2813 A -> No
2813 A -> C No
2963 A -> No
2963 A -> C No
2993 T -> C Yes
3140 -> T No

Variant protein HSSTROL3_P5 (SEQ ID NO:272) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T8 (SEQ ID NO:249) and HSSTROL3_T9 (SEQ ID NO:250). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:270)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSSTROL3_P5 (SEQ ID NO:272) and MM11_HUMAN (SEQ ID NO:270):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P5 (SEQ ID NO:272), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P5 (SEQ ID NO:272), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5 (SEQ ID NO:272), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQ corresponding to amino acids 165-358 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-358 of HSSTROL3_P5 (SEQ ID NO:272), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:967) corresponding to amino acids 359-382 of HSSTROL3_P5 (SEQ ID NO:272), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P5 (SEQ ID NO:272), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:967) in HSSTROL3_P5 (SEQ ID NO:272).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSSTROL3_P5 (SEQ ID NO:272) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:272) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on amino Previously known
acid sequence Alternative amino acid(s) SNP?
38 V -> A Yes
104 R -> P Yes
214 A -> No
323 Q -> H Yes

Variant protein HSSTROL3_P5 (SEQ ID NO:272) is encoded by the following transcript(s): HSSTROL3_T8 (SEQ ID NO:249) and HSSTROL3_T9 (SEQ ID NO:250), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript HSSTROL3_T8 (SEQ ID NO:249) is shown in bold; this coding portion starts at position 24 and ends at position 1169. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:272) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
136 T -> C Yes
334 G -> C Yes
663 G -> No
699 -> T No
992 G -> C Yes
1903 C -> No
1955 C -> A Yes
1981 A -> T Yes
2198 -> G No
2207 -> G No
2221 C -> No
2240 -> A No
2266 T -> C No
2324 A -> No
2324 A -> C No
2474 A -> No
2474 A -> C No
2504 T -> C Yes
2651 -> T No

The coding portion of transcript HSSTROL3_T9 (SEQ ID NO:250) is shown in bold; this coding portion starts at position 24 and ends at position 1169. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:272) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
136 T -> C Yes
334 G -> C Yes
663 G -> No
699 -> T No
992 G -> C Yes
1666 A -> G Yes
1848 A -> G Yes
2389 A -> G Yes
2530 C -> No
2582 C -> A Yes
2608 A -> T Yes
2825 -> G No
2834 -> G No
2848 C -> No
2867 -> A No
2893 T -> C No
2951 A -> No
2951 A -> C No
3101 A -> No
3101 A -> C No
3131 T -> C Yes
3278 -> T No

Variant protein HSSTROL3_P7 (SEQ ID NO:273) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T10 (SEQ ID NO:251). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:270)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSSTROL3_P7 (SEQ ID NO:273) and MM11_HUMAN (SEQ ID NO:270):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P7 (SEQ ID NO:273), comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P7 (SEQ ID NO:273), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7 (SEQ ID NO:273), a second amino acid sequence being at least 90 % homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-359 of HSSTROL3_P7 (SEQ ID NO:273), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:968) corresponding to amino acids 360-370 of HSSTROL3_P7 (SEQ ID NO:273), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P7 (SEQ ID NO:273), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:968) in HSSTROL3_P7 (SEQ ID NO:273).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSSTROL3_P7 (SEQ ID NO:273) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P7 (SEQ ID NO:273) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on Alternative Previously known
amino acid sequence amino acid(s) SNP?
38 V -> A Yes
104 R -> P Yes
214 A -> No
323 Q -> H Yes

Variant protein HSSTROL3_P7 (SEQ ID NO:273) is encoded by the following transcript(s): HSSTROL3_T10 (SEQ ID NO:251), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T10 (SEQ ID NO:251) is shown in bold; this coding portion starts at position 24 and ends at position 1133. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P7 (SEQ ID NO:273) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
136 T -> C Yes
334 G -> C Yes
663 G -> No
699 -> T No
992 G -> C Yes
1386 A -> G Yes
1568 A -> G Yes
2109 A -> G Yes
2250 C -> No
2302 C -> A Yes
2328 A -> T Yes
2545 -> G No
2554 -> G No
2568 C -> No
2587 -> A No
2613 T -> C No
2671 A -> No
2671 A -> C No
2821 A -> No
2821 A -> C No
2851 T -> C Yes
2998 -> T No

Variant protein HSSTROL3_P8 (SEQ ID NO:274) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T11 (SEQ ID NO:252). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:270)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSSTROL3_P8 (SEQ ID NO:274) and MM11_HUMAN (SEQ ID NO:270):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P8 (SEQ ID NO:274), comprising a first amino acid sequence being at least 90 % homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P8 (SEQ ID NO:274), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P8 (SEQ ID NO:274), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLE corresponding to amino acids 165-286 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-286 of HSSTROL3_P8 (SEQ ID NO:274), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRPCLPVPLLLCWPL (SEQ ID NO:969) corresponding to amino acids 287-301 of HSSTROL3_P8 (SEQ ID NO:274), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P8 (SEQ ID NO:274), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRPCLPVPLLLCWPL (SEQ ID NO:969) in HSSTROL3_P8 (SEQ ID NO:274).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSSTROL3_P8 (SEQ ID NO:274) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P8 (SEQ ID NO:274) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on Alternative Previously known
amino acid sequence amino acid(s) SNP?
38 V -> A Yes
104 R -> P Yes
214 A -> No

Variant protein HSSTROL3_P8 (SEQ ID NO:274) is encoded by the following transcript(s): HSSTROL3_T11 (SEQ ID NO:252), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T11 (SEQ ID NO:252) is shown in bold; this coding portion starts at position 24 and ends at position 926. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P8 (SEQ ID NO:274) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
136 T -> C Yes
334 G -> C Yes
663 G -> No
699 -> T No
935 G -> A Yes
948 G -> A Yes
1084 G -> C Yes
1557 C -> No
1609 C -> A Yes
1635 A -> T Yes
1852 -> G No
1861 -> G No
1875 C -> No
1894 -> A No
1920 T -> C No
1978 A -> No
1978 A -> C No
2128 A -> No
2128 A -> C No
2158 T -> C Yes
2305 -> T No

Variant protein HSSTROL3_P9 (SEQ ID NO:275) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T12 (SEQ ID NO:253). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:270)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSSTROL3_P9 (SEQ ID NO:275) and MM11_HUMAN (SEQ ID NO:270):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P9 (SEQ ID NO:275), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1-96 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-96 of HSSTROL3_P9 (SEQ ID NO:275), a second amino acid sequence being at least 90% homologous to RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 113-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 97-147 of HSSTROL3_P9 (SEQ ID NO:275), a bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9 (SEQ ID NO:275), a third amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 149-343 of HSSTROL3_P9 (SEQ ID NO:275), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:968) corresponding to amino acids 344-354 of HSSTROL3_P9 (SEQ ID NO:275), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HSSTROL3_P9 (SEQ ID NO:275), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96-x to 96; and ending at any of amino acid numbers 97+((n-2)−x), in which x varies from 0 to n-2.

3. An isolated polypeptide encoding for a tail of HSSTROL3_P9 (SEQ ID NO:275), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:968) in HSSTROL3_P9 (SEQ ID NO:275).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSSTROL3_P9 (SEQ ID NO:275) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P9 (SEQ ID NO:275) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Amino acid mutations
SNP position(s) on Alternative Previously known
amino acid sequence amino acid(s) SNP?
38 V -> A Yes
198 A -> No
307 Q -> H Yes

Variant protein HSSTROL3_P9 (SEQ ID NO:275) is encoded by the following transcript(s): HSSTROL3_T12 (SEQ ID NO:253), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T12 (SEQ ID NO:253) is shown in bold; this coding portion starts at position 24 and ends at position 1085. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P9 (SEQ ID NO:275) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
136 T -> C Yes
615 G -> No
651 -> T No
944 G -> C Yes
1275 C -> No
1327 C -> A Yes
1353 A -> T Yes
1570 -> G No
1579 -> G No
1593 C -> No
1612 -> A No
1638 T -> C No
1696 A -> No
1696 A -> C No
1846 A -> No
1846 A -> C No
1876 T -> C Yes
2023 -> T No

As noted above, cluster HSSTROL3 features 16 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSSTROL3_node—6 (SEQ ID NO:254) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 1 131
HSSTROL3_T8 (SEQ ID NO:249) 1 131
HSSTROL3_T9 (SEQ ID NO:250) 1 131
HSSTROL3_T10 (SEQID NO:251) 1 131
HSSTROL3_T11 (SEQ ID NO:252) 1 131
HSSTROL3_T12 (SEQ ID NO:253) 1 131

Segment cluster HSSTROL3_node—10 (SEQ ID NO:255) according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEO ID NO:248) 132 313
HSSTROL3_T8 (SEQ ID NO:249) 132 313
HSSTROL3_T9 (SEQ ID NO:250) 132 313
HSSTROL3_T10 (SEQ ID NO:251) 132 313
HSSTROL3_T11 (SEQ ID NO:252) 132 313
HSSTROL3_T12 (SEQ ID NO:253) 132 313

Segment cluster HSSTROL3_node—13 (SEQ ID NO:256) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Seguent
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 362 505
HSSTROL3_T8 (SEQ ID NO:249) 362 505
HSSTROL3_T9 (SEQ ID NO:250) 362 505
HSSTROL3_T10 (SEQ ID NO:251) 362 505
HSSTROL3_T11 (SEQ ID NO:252) 362 505
HSSTROL3_T12 (SEQ ID NO:253) 314 457

Segment cluster HSSTROL3_node—15 (SEQ ID NO:257) according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 506 639
HSSTROL3_T8 (SEQ ID NO:249) 506 639
HSSTROL3_T9 (SEQ ID NO:250) 506 639
HSSTROL3_T10 (SEQ ID NO:251) 506 639
HSSTROL3_T11 (SEQ ID NO:252) 506 639
HSSTROL3_T12 (SEQ ID NO:253) 458 591

Segment cluster HSSTROL3_node—19 (SEQ ID NO:258) according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 699 881
HSSTROL3_T8 (SEQ ID NO:249) 699 881
HSSTROL3_T9 (SEQ ID NO:250) 699 881
HSSTROL3_T10 (SEQ ID NO:251) 699 881
HSSTROL3_T11 (SEQ ID NO:252) 699 881
HSSTROL3_T12 (SEQ ID NO:253) 651 833

Segment cluster HSSTROL3_node—21 (SEQ ID NO:259) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 882 1098
HSSTROL3_T8 (SEQ ID NO:249) 882 1098
HSSTROL3_T9 (SEQ ID NO:250) 882 1098
HSSTROL3_T10 (SEQ ID NO:251) 882 1098
HSSTROL3_T11 (SEQ ID NO:252) 974 1190
HSSTROL3_T12 (SEQ ID NO:253) 834 1050

Segment cluster HSSTROL3_node—24 (SEQ ID NO:260) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T8 (SEQ ID NO:249) and HSSTROL3_T9 (SEQ ID NO:250). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T8 (SEQ ID NO:249) 1099 1236
HSSTROL3_T9 (SEQ ID NO:250) 1099 1236

Segment cluster HSSTROL3_node—25 (SEQ ID NO:261) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T8 (SEQ ID NO:249). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T8 (SEQ ID NO:249) 1237 1536

Segment cluster HSSTROL3_node—26 (SEQ ID NO:262) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250) and HSSTROL3_T11 (SEQ ID NO:252). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 1099 1240
HSSTROL3_T8 (SEQ ID NO:249) 1537 1678
HSSTROL3_T9 (SEQ ID NO:250) 1237 1378
HSSTROL3_T11(SEQ ID NO:252) 1191 1332

Segment cluster HSSTROL3_node—28 (SEQ ID NO:263) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T9 (SEQ ID NO:250) and HSSTROL3_T1O (SEQ ID NO:251). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 1357 2283
HSSTROL3_T9 (SEQ ID NO:250) 1495 2421
HSSTROL3_T10 (SEQ ID NO:251) 1215 2141

Segment cluster HSSTROL3_node—29 (SEQ ID NO:264) according to the present invention is supported by 109 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T11 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 2284 3194
HSSTROL3_T8 (SEQ ID NO:249) 1795 2705
HSSTROL3_T9 (SEQ ID NO:250) 2422 3332
HSSTROL3_T10 (SEQ IDNO:251) 2142 3052
HSSTROL3_T11 (SEQ ID NO:252) 1449 2359
HSSTROL3_T12 (SEQ ID NO:253) 1167 2077

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HSSTROL3_node—11 (SEQ ID NO:265) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251) and HSSTROL3_T11 (SEQ ID NO:252). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 314 361
HSSTROL3_T8 (SEQ ID NO:249) 314 361
HSSTROL3_T9 (SEQ ID NO:250) 314 361
HSSTROL3_T10 (SEQ ID NO:251) 314 361
HSSTROL3_T11 (SEQ ID NO:252) 314 361

Segment cluster HSSTROL3_node—17 (SEQ ID NO:266) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 640 680
HSSTROL3_T8 (SEQ ID NO:249) 640 680
HSSTROL3_T9 (SEQ ID NO:250) 640 680
HSSTROL3_T10 (SEQ ID NO:251) 640 680
HSSTROL3_T11 (SEQ ID NO:252) 640 680
HSSTROL3_T12 (SEQ ID NO:253) 592 632

Segment cluster HSSTROL3_node—18 (SEQ ID NO:267) according to the present invention can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 681 698
HSSTROL3_T8 (SEQ ID NO:249) 681 698
HSSTROL3_T9 (SEQ ID NO:250) 681 698
HSSTROL3_T10 (SEQ ID NO:251) 681 698
HSSTROL3_T11 (SEQ ID NO:252) 681 698
HSSTROL3_T12 (SEQ ID NO:253) 633 650

Segment cluster HSSTROL3_node—20 (SEQ ID NO:268) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T11 (SEQ ID NO:252). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T11 (SEQ ID NO:252) 882 973

Segment cluster HSSTROL3_node—27 (SEQ ID NO:269) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:248), HSSTROL3_T8 (SEQ ID NO:249), HSSTROL3_T9 (SEQ ID NO:250), HSSTROL3_T10 (SEQ ID NO:251), HSSTROL3_T11 (SEQ ID NO:252) and HSSTROL3_T12 (SEQ ID NO:253). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO:248) 1241 1356
HSSTROL3_T8 (SEQ ID NO:249) 1679 1794
HSSTROL3_T9 (SEQ ID NO:250) 1379 1494
HSSTROL3_T10 (SEQ ID NO:251) 1099 1214
HSSTROL3_T11 (SEQ ID NO:252) 1333 1448
HSSTROL3_T12 (SEQ ID NO:253) 1051 1166

Variant protein alignment to the previously known protein:

Sequence name: MM11_HUMAN (SEQ ID NO:270)

Sequence documentation:

Alignment of: HSSTROL3_P4 (SEQ ID NO:271)×MM11_HUMAN (SEQ ID NO:270).

Alignment segment 1/1:

Quality: 4444.00
Escore: 0
Matching length: 445 Total length: 445
Matching Percent 99.78 Matching Percent Identity: 99.78
Similarity:
Total Percent Similarity: 99.78 Total Percent Identity: 99.78
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
         .         .         .         .         .
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
         .         .         .         .         .
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
         .         .         .         .         .
151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
||||||||||||| ||||||||||||||||||||||||||||||||||||
151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
         .         .         .         .         .
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
         .         .         .         .         .
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
         .         .         .         .         .
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
         .         .         .         .         .
351 QGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKI 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 QGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPEKNKI 400
         .         .         .         .
401 YFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG 445
|||||||||||||||||||||||||||||||||||||||||||||
401 YFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG 445

Sequence name: MM11_HUMAN (SEQ ID NO:270)

Sequence documentation:

Alignment of: HSSTROL3_P5 (SEQ ID NO:272)×MM11_HUMAN (SEQ ID NO:270).

Alignment segment 1/1:

Quality: 3566.00
Escore: 0
Matching length: 358 Total length: 358
Matching Percent 99.72 Matching Percent Identity: 99.72
Similarity:
Total Percent Similarity: 99.72 Total Percent Identity: 99.72
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
         .         .         .         .         .
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
         .         .         .         .         .
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
         .         .         .         .         .
151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
||||||||||||| ||||||||||||||||||||||||||||||||||||
151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
         .         .         .         .         .
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
         .         .         .         .         .
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
         .         .         .         .         .
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
351 QGHIWFFQ 358
||||||||
351 QGHIWFFQ 358

Sequence name: MM11_HUMAN (SEQ ID NO:270)

Sequence documentation:

Alignment of: HSSTROL3_P7 (SEQ ID NO:273)×MM11_HUMAN (SEQ ID NO:270).

Alignment segment 1/1:

Quality: 3575.00
Escore: 0
Matching length: 359 Total length: 359
Matching Percent 99.72 Matching Percent Identity: 99.72
Similarity:
Total Percent Similarity: 99.72 Total Percent Identity: 99.72
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
         .         .         .         .         .
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
         .         .         .         .         .
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
         .         .         .         .         .
151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
||||||||||||| ||||||||||||||||||||||||||||||||||||
151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
         .         .         .         .         .
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
         .         .         .         .         .
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
         .         .         .         .         .
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
351 QGHIWFFQG 359
|||||||||
351 QGHIWFFQG 359

Sequence name: MM11_HUMAN (SEQ ID NO:270)

Sequence documentation:

Alignment of: HSSTROL3_P8 (SEQ ID NO:274)×MM11_HUMAN (SEQ ID NO:270).

Alignment segment 1/1:

Quality: 2838.00
Escore: 0
Matching length: 286 Total length: 286
Matching Percent 99.65 Matching Percent Identity: 99.65
Similarity:
Total Percent Similarity: 99.65 Total Percent Identity: 99.65
Gaps: 0

Alignment:

         .         .         .         .         .
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
         .         .         .         .         .
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
         .         .         .         .         .
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
         .         .         .         .         .
151 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
||||||||||||| ||||||||||||||||||||||||||||||||||||
151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
         .         .         .         .         .
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
         .         .         .
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE 286
||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE 286

Sequence name: MM11_HUMAN (SEQ ID NO:270)

Sequence documentation:

Alignment of: HSSTROL3_P9 (SEQ ID NO:275)×MM11_HUMAN (SEQ ID NO:270).

Alignment segment 1/1:

Quality: 3316.00
Escore: 0
Matching length: 343 Total length: 359
Matching Percent 99.71 Matching Percent Identity: 99.71
Similarity:
Total Percent Similarity: 95.26 Total Percent Identity: 95.26
Gaps: 1

Alignment:

         .         .         .         .         .
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQP 50
         .         .         .         .         .
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK.... 96
||||||||||||||||||||||||||||||||||||||||||||||
51 WHAALPSSPAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVL 100
         .         .         .         .         .
97 ............RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 134
            ||||||||||||||||||||||||||||||||||||||
101 SGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHE 150
         .         .         .         .         .
135 GRADIMIDFARYWHGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 184
||||||||||||| ||||||||||||||||||||||||||||||||||||
151 GRADIMIDFARYWDGDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWT 200
         .         .         .         .         .
185 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 234
||||||||||||||||||||||||||||||||||||||||||||||||||
201 IGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALMSAFYTFRYPLSLSPDDC 250
         .         .         .         .         .
235 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 284
||||||||||||||||||||||||||||||||||||||||||||||||||
251 RGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDA 300
         .         .         .         .         .
285 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 334
||||||||||||||||||||||||||||||||||||||||||||||||||
301 VSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDA 350
335 QGHIWFFQG 343
|||||||||
351 QGHIWFFQG 359

Expression of Stromelysin-3 Precursor (EC 3.4.24.-) (Matrix Metalloproteinase-11) (MMP-11) (ST3) SL-3 HSSTROL3 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 seg24 (SEQ ID NO:869) in Normal and Cancerous Breast Tissues

Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3 transcripts detectable by or according to seg24 HSSTROL3 seg24 (SEQ ID NO:869) amplicon(s) and HSSTROL3 seg24F (SEQ ID NO:867) and HSSTROL3 seg24R (SEQ ID NO:868) primers was measured by real time PCR. In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)) SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 29A is a histogram showing over expression of the above-indicated Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.

As is evident from FIG. 29A, the expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos.56-60, 63-67 Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 20 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) transcripts detectable by the above amplicon(s) in Breast cancer samples versus the normal tissue samples was determined by T test as 6.46E-03.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.12E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL3 seg24F forward primer (SEQ ID NO:867); and HSSTROL3 seg24R reverse primer (SEQ ID NO:868).The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: HSSTROL3 seg24 (SEQ ID NO:869).

HSSTROL3 seg24 Forward Primer (SEQ ID NO:867):
ATTTCCATCCTCAACTGGCAGA
HSSTROL3 seg24 Reverse Primer (SEQ ID NO:868):
TGCCCTGGAACCCACG
HSSTROL3 seg24 Amplicon: (SEQ ID NO:869):
ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTGGAGCATTGCAGATGCC
AGGGACTTCACAAATGAAGGCACAGCATGGGAAACCTGCGTGGGTTCCAG
GGCA

Expression of Stromelysin-3 Precursor (EC 3.4.24.-) (Matrix Metalloproteinase-11) (MMP-11) (ST3) (SL-3)HSSTROL3 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 seg24 (SEQ ID NO:869) in Different Normal Tissues

Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) transcripts detectable by or according to HSSTROL3 seg24 (SEQ ID NO:869) amplicon(s) and HSSTROL3 seg24F (SEQ ID NO:867) and HSSTROL3 seg24R (SEQ ID NO:868) was measured by real time PCR. In parallel the expression of four housekeeping genes UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (sample Nos. 15-17 Table 2,“Tissue samples on normal panel” above), to obtain a value of relative expression of each sample relative to median of the lung samples. Primers and amplicon are as above.

The results are presented in FIG. 29B, demonstrating the expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:869), in different normal tissues.

Expression of Stromelysin-3 Precursor (EC 3.4.24.-) (Matrix Metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 junc20-21 (SEQ ID NO:872) in Normal and Cancerous Breast Tissues

Expression of Stromelysin-3 precursor transcripts detectable by or according to junc20-21, HSSTROL3junc20-21 (SEQ ID NO:872) amplicon(s) and primers HSSTROL3junc20-21F (SEQ ID NO:870) and HSSTROL3junc20-21R (SEQ ID NO:871) was measured by real time PCR. It should be noted that for this experiment, RNA was obtained from Clontech (Franklin Lakes, N.J. USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, Calif. 94545 USA www.biochain.com), ABS (Wilmington, Del. 19801, USA, www.absbioreagents.com), GOG for ovary samples—Pediatic Cooperative Human Tissue Network, Gynecologic Oncology Group Tissue Bank, Children Hospital of Columbus (Columbus Ohio 43205 USA) or Ambion (Austin, Tex. 78744 USA, www.ambion.com). Alternatively, RNA was generated from tissue samples using TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion).

In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 30A is a histogram showing over expression of the above-indicated Stromelysin-3 precursor transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 30A, the expression of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above). Notably an over-expression of at least 5 fold was found in 13 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 1.28E-02.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 4.26E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL junc20-21F (SEQ ID NO:870) forward primer; and HSSTROL junc20-21R (SEQ ID NO:871) reverse primer.

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: HSSTROL junc20-21 (SEQ ID NO:872).

Forward primer HSSTROL junc20-21F (SEQ ID NO:870):
TCTGCTGGCCACTGTGACTG
Reverse primer HSSTROL junc20-21R (SEQ ID NO:871):
GAAGAAAAAGAGCTCGCCTCG
Amplicon HSSTROL junc20-21 (SEQ ID NO:872):
TCTGCTGGCCACTGTGACTGCAGCATATGCCCTCAGCATGTGTCCCTCTC
TCCCACCCCAGCCAGACGCCCCGCCAGATGCCTGTGAGGCCTCCTTTGAC
GCGGTCTCCACCATCCGAGGCGAGCTCTTTTTCTTC

Expression of Stromelysin-3 Precursor (EC 3.4.24.-) (Matrix Metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 junc21-27 (SEQ ID NO:875) in Normal and Cancerous Breast Tissues

Expression of Stromelysin-3 precursor transcripts detectable by or according to junc21-27, HSSTROL3 junc21-27 (SEQ ID NO:875) amplicon(s) and primers HSSTROL3junc21-27F (SEQ ID NO:873) and HSSTROL3junc21-27R (SEQ ID NO:874) was measured by real time PCR (RNA was as for the experiment above). In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 30B is a histogram showing over expression of the above-indicated Stromelysin-3 precursor transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 30B, the expression of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1: Tissue samples in testing panel, above). Notably an over-expression of at least 20 fold was found in 20 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 5.98E-03.

Threshold of 20 fold overexpression was found to differentiate between cancer and normal samples with P value of 3.66E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL junc21-27F forward primer (SEQ ID NO:873); and HSSTROL junc21-27R reverse primer (SEQ ID NO:874).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: HSSTROL junc21-27 (SEQ ID NO:875).

Forward primer HSSTROL junc21-27F (SEQ ID NO:873):
ACATTTGGTTCTTCCAAGGGACTAC
Reverse primer HSSTROL junc21-27R (SEQ ID NO:874):
TCGATCTCAGAGGGCACCC
Amplicon HSSTROL junc21-27 (SEQ ID NO:875):
ACATTTGGTTCTTCCAAGGGACTACTGGCGTTTCCACCCCAGCACCCGGC
GTGTAGACAGTCCCGTGCCCCGCAGGGCCACTGACTGGAGAGGGGTGCCC
TCTGAGATCGA

Expression of Stromelysin-3 Precursor (EC 3.4.24.-) (Matrix Metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 seg25 (SEQ ID NO:878) in Normal and Cancerous Breast Tissues

Expression of Stromelysin-3 precursor transcripts detectable by or according to seg25, HSSTROL3 junc21-27 (SEQ ID NO:878) amplicon(s) and primers HSSTROL3junc21-27F (SEQ ID NO:876) and HSSTROL3junc21-27R (SEQ ID NO:877) was measured by real time PCR (RNA was as for the experiment above). In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 30C is a histogram showing over expression of the above-indicated Stromelysin-3 precursor transcripts in cancerous breast samples relative to the normal samples .

As is evident from FIG. 30C, the expression of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1: Tissue samples in testing panel, above). Notably an over-expression of at least 5 fold was found in 20 out of 28 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Stromelysin-3 precursor transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 5.79E-02.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.75E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL seg25F forward primer (SEQ ID NO:876); and HSSTROL seg25R reverse primer (SEQ ID NO:877).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: HSSTROL seg25 (SEQ ID NO:878).

Forward primer HSSTROL seg25F (SEQ ID NO:876):
CACTGCCCCAGCTTATCCC
Reverse primer HSSTROL seg25R (SEQ ID NO:877):
CTCTCCCAGCCTCAGTTTCCT
Amplicon HSSTROL seg25 (SEQ ID NO:878):
CACTGCCCCAGCTTATCCCAGGCCTCCCGCTTCCCTCTGCGGGTGGGGTG
CTGAGCAGGCATTATTGGCCTGCATGTTTTACTGATGAGGAAACTGAGGC
TGGGAGAG

Description for Cluster AY180924

Cluster AY180924 features 1 transcript(s) and 3 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
AY180924_PEA_1_T1 276

TABLE 2
Segments of interest
Segment Name Sequence ID No.
AY180924_PEA_1_node_3 277
AY180924_PEA_1_node_0 278
AY180924_PEA_1_node_2 279

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
AY180924_PEA_1_P3 281

These sequences are variants of the known protein Latherin precursor (SEQ ID NO:280) (SwissProt accession identifier LATH_HUMAN; known also according to the synonyms Breast cancer and salivary gland expressed protein), SEQ ID NO: 280, referred to herein as the previously known protein.

Protein Latherin precursor (SEQ ID NO:280) is known or believed to have the following function(s): surfactant properties. The sequence for protein Latherin precursor (SEQ ID NO:280) is given at the end of the application, as “Latherin precursor (SEQ ID NO:280) amino acid sequence”. The protein Latherin localization is believed to be Secreted.

As noted above, cluster AY180924 features 1 transcript, which were listed in Table 1 above. This transcript encode for protein which is a variant of protein Latherin precursor (SEQ ID NO:280). A description of the variant protein according to the present invention is now provided.

Variant protein AY180924_PEA—1_P3 (SEQ ID NO:281) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AY180924_PEA—1_T1 (SEQ ID NO:276). An alignment is given to the known protein (Latherin precursor (SEQ ID NO:280)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between AY180924_PEA—1_P3 (SEQ ID NO:281) and LATH_HUMAN (SEQ ID NO:280):

1. An isolated chimeric polypeptide encoding for AY180924_PEA—1_P3 (SEQ ID NO:281), comprising a first amino acid sequence being at least 90% homologous to MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN corresponding to amino acids 1-33 of LATH_HUMAN (SEQ ID NO:280), which also corresponds to amino acids 1-33 of AY180924_PEA—1_P3 (SEQ ID NO:281) , and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY (SEQ ID NO:971) corresponding to amino acids 34-64 of AY180924_PEA—1_P3 (SEQ ID NO:281), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of AY180924_PEA—1_P3 (SEQ ID NO:281) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY (SEQ ID NO:971) in AY180924_PEA—1_P3(SEQ ID NO:281).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein AY180924_PEA—1_P3 (SEQ ID NO:281) is encoded by the following transcript(s): AY180924_PEA—1_T1 (SEQ ID NO:276), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AY180924_PEA—1_T1 (SEQ ID NO:276) is shown in bold; this coding portion starts at position 73 and ends at position 264. The transcript also has the following SNPs as listed in Table 4 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AY180924_PEA—1_P3 (SEQ ID NO:281) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 4
Nucleic acid SNPs
SNP position on nucleotide Alternative Previously known
sequence nucleic acid SNP?
361 C -> T Yes
459 C -> A Yes

As noted above, cluster AY180924 features 3 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster AY180924_PEA—1_node—3 (SEQ ID NO:277) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AY180924_PEA—1_T1 (SEQ ID NO:276). Table 5 below describes the starting and ending position of this segment on each transcript.

TABLE 5
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
AY180924_PEA_1_T1 173 657
(SEQ ID NO: 276)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster AY180924_PEA—1_node—0 (SEQ ID NO:278) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AY180924_PEA—1_T1 (SEQ ID NO:276). Table 6 below describes the starting and ending position of this segment on each transcript.

TABLE 6
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
AY180924_PEA_1_T1 1 58
(SEQ ID NO: 276)

Segment cluster AY180924_PEA—1_node—2 (SEQ ID NO:279) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AY180924_PEA—1_T1 (SEQ ID NO:276). Table 7 below describes the starting and ending position of this segment on each transcript.

TABLE 7
Segment location on transcripts
Segment
Transcript name starting position Segment ending position
AY180924_PEA_1_T1 59 172
(SEQ ID NO: 276)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/FepOCusBjG/YVh7Ev127H:LATH_HUMAN (SEQ ID NO:280)

Sequence documentation:

Alignment of: AY180924_PEA—1_P3 (SEQ ID NO:281)×LATH_HUMAN (SEQ ID NO:280).

Alignment segment 1/1:

Quality: 300.00
Escore: 0
Matching length: 33 Total length: 33
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent 100.00 Total Percent Identity: 100.00
Similarity:
Gaps: 0

Alignment:

1 MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN 33
|||||||||||||||||||||||||||||||||
1 MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN 33

Description for Cluster R75793

Cluster R75793 features 3 transcript(s) and 9 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
R75793_PEA_1_T1 282
R75793_PEA_1_T3 283
R75793_PEA_1_T5 284

TABLE 2
Segments of interest
Segment Name Sequence ID No.
R75793_PEA_1_node_0 285
R75793_PEA_1_node_9 286
R75793_PEA_1_node_11 287
R75793_PEA_1_node_14 288
R75793_PEA_1_node_4 289
R75793_PEA_1_node_5 290
R75793_PEA_1_node_6 291
R75793_PEA_1_node_8 292
R75793_PEA_1_node_13 293

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
R75793_PEA_1_P2 295 R75793_PEA_1_T1 (SEQ ID
NO: 282)
R75793_PEA_1_P5 296 R75793_PEA_1_T5 (SEQ ID
NO: 284)
R75793_PEA_1_P6 297 R75793_PEA_1_T3 (SEQ ID
NO: 283)

Cluster R75793 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 31 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 31 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 4
Normal tissue distribution
Name of Tissue Number
epithelial 16
general 5
Breast 457

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
epithelial 3.3e−01 5.0e−01 9.2e−17 4.0 2.7e−07 2.0
general 1.3e−01 2.0e−01 3.4e−33 8.0 2.0e−17 3.9
Breast 5.9e−01 7.1e−01 1.2e−07 2.1 1.4e−02 1.0

As noted above, cluster R75793 features 3 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein R75793_PEA—1_P2 (SEQ ID NO:295) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R75793_PEA—1_T1 (SEQ ID NO:282). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between R75793_PEA—1_P2 (SEQ ID NO:295) and Q96DR8 (SEQ ID NO: 294):

1. An isolated chimeric polypeptide encoding for R75793_PEA—1_P2 (SEQ ID NO:295), comprising a first amino acid sequence being at least 90% homologous to MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAATTATTAAPT TATTAASTTARKDIP corresponding to amino acids 1-74 of Q96DR8 (SEQ ID NO:294), which also corresponds to amino acids 1-74 of R75793_PEA—1_P2 (SEQ ID NO:295), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AP corresponding to amino acids 75-76 of R75793_PEA—1_P2 (SEQ ID NO:295), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R75793_PEA—1_P2 (SEQ ID NO:295) is encoded by the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R75793_PEA—1_T1 (SEQ ID NO:282) is shown in bold; this coding portion starts at position 69 and ends at position 296. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA—1_P2 (SEQ ID NO:295) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
15 C -> A Yes
59 G -> T Yes
179 T -> C No
179 T -> G No
227 G -> A Yes
516 A -> T No

Variant protein R75793_PEA—1_P5 (SEQ ID NO:296) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R75793_PEA—1_T5 (SEQ ID NO:284). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R75793_PEA—1_P5 (SEQ ID NO:296) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA—1_P5 (SEQ ID NO:296) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
54 H -> R Yes

Variant protein R75793_PEA—1_P5 (SEQ ID NO:296) is encoded by the following transcript(s): R75793_PEA—1_T5 (SEQ ID NO:284), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R75793_PEA—1_T5 (SEQ ID NO:284) is shown in bold; this coding portion starts at position 69 and ends at position 383. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA—1_P5 (SEQ ID NO:296) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
15 C -> A Yes
59 G -> T Yes
229 A -> G Yes

Variant protein R75793_PEA—1_P6 (SEQ ID NO:297) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R75793_PEA—1_T3 (SEQ ID NO:283). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R75793_PEA—1_P6 (SEQ ID NO:297) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA—1_P6 (SEQ ID NO:297) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
16 R -> Q Yes

Variant protein R75793_PEA—1_P6 (SEQ ID NO:297) is encoded by the following transcript(s): R75793_PEA—1_T3 (SEQ ID NO:283), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R75793_PEA—1_T3 (SEQ ID NO:283) is shown in bold; this coding portion starts at position 329 and ends at position 502. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R75793_PEA—1_P6 (SEQ ID NO:297) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
327 T -> C No
327 T -> G No
375 G -> A Yes
635 A -> T No

As noted above, cluster R75793 features 9 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster R75793_PEA—1_node—0 (SEQ ID NO:285) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T3 (SEQ ID NO:283). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T3 (SEQ ID NO: 283) 1 274

Segment cluster R75793_PEA—1_node—9 (SEQ ID NO:286) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T5 (SEQ ID NO:284). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T5 (SEQ ID NO: 284) 169 491

Segment cluster R75793_PEA—1_node—11 (SEQ ID NO:287) according to the present invention is supported by 59 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282) and R75793_PEA—1_T3 (SEQ ID NO:283). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 169 291
R75793_PEA_1_T3 (SEQ ID NO: 283) 317 439

Segment cluster R75793_PEA—1_node—14 (SEQ ID NO:288) according to the present invention is supported by 41 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282) and R75793_PEA—1_T3 (SEQ ID NO:283). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 321 527
R75793_PEA_1_T3 (SEQ ID NO: 283) 440 646

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster R75793_PEA—1_node—4 (SEQ ID NO:289) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282) and R75793_PEA—1_T5 (SEQ ID NO:284). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 1 41
R75793_PEA_1_T5 (SEQ ID NO: 284) 1 41

Segment cluster R75793_PEA—1_node—5 (SEQ ID NO:290) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282) and R75793_PEA—1_T5 (SEQ ID NO:284). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 42 74
R75793_PEA_1_T5 (SEQ ID NO: 284) 42 74

Segment cluster R75793_PEA—1_node—6 (SEQ ID NO:291) according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282) and R75793_PEA—1_T5 (SEQ ID NO:284). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 75 126
R75793_PEA_1_T5 (SEQ ID NO: 284) 75 126

Segment cluster R75793_PEA—1_node—8 (SEQ ID NO:292) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282), R75793_PEA—1_T3 (SEQ ID NO:283) and R75793_PEA1_T5 (SEQ ID NO:284). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 127 168
R75793_PEA_1_T3 (SEQ ID NO: 283) 275 316
R75793_PEA_1_T5 (SEQ ID NO: 284) 127 168

Segment cluster R75793_PEA—1_node—13 (SEQ ID NO:293) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R75793_PEA—1_T1 (SEQ ID NO:282). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
R75793_PEA_1_T1 (SEQ ID NO: 282) 292 320

Variant protein alignment to the previously known protein:

Sequence name: Q96DR8 (SEQ ID NO:294)

Sequence documentation:

Alignment of: R75793_PEA—1_P2 (SEQ ID NO:295)×Q96DR8 (SEQ ID NO:294).

Alignment segment 1/1:

Quality: 681.00
Escore: 0
Matching length: 74 Total length: 74
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent 100.00 Total Percent Identity: 100.00
Similarity:
Gaps: 0

Alignment:

         .         .         .         .         .
1 MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAA 50
         .         .
51 TTATTAAPTTATTAASTTARKDIP 74
||||||||||||||||||||||||
51 TTATTAAPTTATTAASTTARKDIP 74

Expression of Homo Sapiens Small Breast Epithelial Mucin (LOC118430) R75793 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name R75793 junc11-13 (SEQ ID NO:881) in Normal and Cancerous Breast Tissues

Expression of Homo sapiens small breast epithelial mucin (LOC118430) transcripts detectable by or according to junc11-13, R75793 junc11-13 (SEQ ID NO:881) amplicon(s) and primers R75793 junc11-13F (SEQ ID NO:879) and R75793 junc11-13R (SEQ ID NO:880) was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) and G6PD. (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921 ), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a failure of this particular experiment.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R75793 junc11-13F forward primer (SEQ ID NO:879); and R75793 junc11-13R reverse primer (SEQ ID NO:880).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R75793 junc11-13 (SEQ ID NO:881).

Forward primer R75793 junc11-13F (SEQ ID NO:879):
TGATGATGAAGCCCCTGATG
Reverse primer R75793 junc11-13R (SEQ ID NO:880):
TATTGTCAAGGGGCTGGAATGT
Amplicon R75793 junc11-13 (SEQ ID NO:881):
TGATGATGAAGCCCCTGATGCTGAAACCACTGCTGCTGCAACCACTGCGA
CCACTGCTGCTCCTACCACTGCAACCACCGCTGCTTCTACCACTGCTCGT
AAAGACATTCCAGCCCCTTGACAATA

Expression of Homo Sapiens Small Breast Epithelial Mucin (LOC118430) R75793 Transcripts Which Are Detectable by Amplicon as Depicted in Sequence Name R75793 seg9 (SEQ ID NO:884) in Normal and Cancerous Breast Tissues

Expression of Homo sapiens small breast epithelial mucin (LOC118430) transcripts detectable by or according to seg9, R75793seg9 (SEQ ID NO:884) amplicon(s) and primers R75793 seg9F (SEQ ID NO:882) and R75793seg9R (SEQ ID NO:883) was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a failure of this particular experiment.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R75793seg9F forward primer (SEQ ID NO:882); and R75793seg9R reverse primer (SEQ ID NO:883).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R75793seg9 (SEQ ID NO:884).

Forward primer R75793seg9F (SEQ ID NO:882):
TCCAGCAATAACCATTTTTCACTTC
Reverse primer R75793seg9R (SEQ ID NO:883):
GCTTTCACAGACTTTTGCTTAGGATT
Amplicon R75793seg9 (SEQ ID NO:884):
TCCAGCAATAACCATTTTTCACTTCCAGCCTCATGTCAAACAGCCAGTTT
CCATGTGGATAGTCTTTGTTATAAGGAATCCTAAGCAAAAGTCTGTGAAA
GC

Description for Cluster HUMCA1XIA

Cluster HUMCA1XIA features 4 transcript(s) and 46 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HUMCA1XIA_T16 298
HUMCA1XIA_T17 299
HUMCA1XIA_T19 300
HUMCA1XIA_T20 301

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HUMCA1XIA_node_0 302
HUMCA1XIA_node_2 303
HUMCA1XIA_node_4 304
HUMCA1XIA_node_6 305
HUMCA1XIA_node_8 306
HUMCA1XIA_node_9 307
HUMCA1XIA_node_18 308
HUMCA1XIA_node_54 309
HUMCA1XIA_node_55 310
HUMCA1XIA_node_92 311
HUMCA1XIA_node_11 312
HUMCA1XIA_node_15 313
HUMCA1XIA_node_19 314
HUMCA1XIA_node_21 315
HUMCA1XIA_node_23 316
HUMCA1XIA_node_25 317
HUMCA1XIA_node_27 318
HUMCA1XIA_node_29 319
HUMCA1XIA_node_31 320
HUMCA1XIA_node_33 321
HUMCA1XIA_node_35 322
HUMCA1XIA_node_37 323
HUMCA1XIA_node_39 324
HUMCA1XIA_node_41 325
HUMCA1XIA_node_43 326
HUMCA1XIA_node_45 327
HUMCA1XIA_node_47 328
HUMCA1XIA_node_49 329
HUMCA1XIA_node_51 330
HUMCA1XIA_node_57 331
HUMCA1XIA_node_59 332
HUMCA1XIA_node_62 333
HUMCA1XIA_node_64 334
HUMCA1XIA_node_66 335
HUMCA1XIA_node_68 336
HUMCA1XIA_node_70 337
HUMCA1XIA_node_72 338
HUMCA1XIA_node_74 339
HUMCA1XIA_node_76 340
HUMCA1XIA_node_78 341
HUMCA1XIA_node_81 342
HUMCA1XIA_node_83 343
HUMCA1XIA_node_85 344
HUMCA1XIA_node_87 345
HUMCA1XIA_node_89 346
HUMCA1XIA_node_91 347

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
HUMCA1XIA_P14 350 HUMCA1XIA_T16
(SEQ ID NO:298)
HUMCA1XIA_P15 351 HUMCA1XIA_T17
(SEQ ID NO:299)
HUMCA1XIA_P16 352 HUMCA1XIA_T19
(SEQ ID NO:300)
HUMCA1XIA_P17 353 HUMCA1XIA_T20
(SEQ ID NO:301)

These sequences are variants of the known protein Collagen alpha 1 (SEQ ID NO:348) (SwissProt accession identifier CA1B_HUMAN; known also according to the synonyms XI), SEQ ID NO:348, referred to herein as the previously known protein.

Protein Collagen alpha 1 (SEQ ID NO:348) is known or believed to have the following function(s): May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils. The sequence for protein Collagen alpha 1 (SEQ ID NO:348) is given at the end of the application, as “Collagen alpha 1 (SEQ ID NO:348) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
 625 G -> V (in STL2). /FTId = VAR_013583.
 676 G -> R (in STL2; overlapping phenotype with
Marshall syndrome). /FTId = VAR_013584.
921-926 Missing (in STL2; overlapping phenotype with
Marshall syndrome). /FTId = VAR_013585.
1313-1315 Missing (in STL2; overlapping phenotype with
Marshall syndrome). /FTId = VAR_013586.
1516 G -> V (in STL2; overlapping phenotype with
Marshall syndrome). /FTId = VAR_013587.
941-944 KDGL -> RMGC
 986 Y -> H
1074 R -> P
1142 G -> D
1218 M -> W
1758 T -> A
1786 S -> N

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cartilage condensation; vision; hearing; cell-cell adhesion; extracellular matrix organization and biogenesis, which are annotation(s) related to Biological Process; extracellular matrix structural protein; extracellular matrix protein, adhesive, which are annotation(s) related to Molecular Function; and extracellular matrix; collagen; collagen type XI, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HUMCA1XIA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 32 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 32 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

TABLE 5
Normal tissue distribution
Name of Tissue Number
Adrenal 0
Bone 207
Brain 13
Colon 0
epithelial 11
general 11
head and neck 0
kidney 0
Lung 0
Breast 8
pancreas 0
stomach 73
Uterus 9

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 4.2e−01 1.9e−01 9.6e−02 3.4 8.2e−02 3.6
Bone 2.4e−01 6.3e−01 7.7e−10 4.3 5.3e−03 1.6
Brain 5.0e−01 6.9e−01 1.8e−01 2.1 4.2e−01 1.3
Colon 1.3e−02 2.9e−02 2.4e−01 3.0 3.5e−01 2.4
epithelial 3.9e−04 3.2e−03 1.3e−03 2.3 1.8e−02 1.7
general 5.6e−05 1.6e−03 9.5e−17 4.5 1.1e−09 2.8
head and neck 1.2e−01 2.1e−01 1 1.3 1 1.1
kidney 6.5e−01 7.2e−01 3.4e−01 2.4 4.9e−01 1.9
Lung 5.3e−02 9.1e−02 5.5e−05 7.3 5.0e−03 4.0
Breast 4.3e−01 5.6e−01 6.9e−01 1.4 8.2e−01 1.1
pancreas 3.3e−01 1.8e−01 4.2e−01 2.4 1.5e−01 3.7
stomach 5.0e−01 6.1e−01 6.9e−01 1.0 6.7e−01 0.8
Uterus 7.1e−01 7.0e−01 6.6e−01 1.1 6.4e−01 1.1

As noted above, cluster HUMCA1XIA features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Collagen alpha 1 (SEQ ID NO:348). A description of each variant protein according to the present invention is now provided.

Variant protein HUMCA1XIA_P14 (SEQ ID NO:350) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T16 (SEQ ID NO:298). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:348)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMCA1XIA_P14 (SEQ ID NO:350) and CA1B_HUMAN_V5 (SEQ ID NO: 349):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P14 (SEQ ID NO:350), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVK GADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPT GDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPR GQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGP PGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQG LPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP V corresponding to amino acids 1-1056 of CA1B_HUMAN_V5 (SEQ ID NO:349), which also corresponds to amino acids 1-1056 of HUMCA1XIA_P14 (SEQ ID NO:350), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:972) corresponding to amino acids 1057-1081 of HUMCA1XIA_P14 (SEQ ID NO:350), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCA1XIA_P14 (SEQ ID NO:350), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:972) in HUMCA1XIA_P14 (SEQ ID NO:350).

It should be noted that the known protein sequence (CA1B_HUMAN; SEQ ID NO:348) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CA1B_HUMAN_V5 (SEQ ID NO:349) (SEQ ID NO:349). These changes were previously known to occur and are listed in the table below.

TABLE 7
Changes to CA1B_HUMAN_V5 (SEQ ID NO: 349)
SNP position(s) on
amino acid sequence Type of change
987 conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMCA1XIA_P14 (SEQ ID NO:350) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P14 (SEQ ID NO:350) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
8 W -> G Yes
46 D -> E Yes
559 G -> S Yes
832 G -> * Yes
986 H -> Y Yes
1061 I -> M Yes
1070 V -> A Yes

Variant protein HUMCA1XIA_P14 (SEQ ID NO:350) is encoded by the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T16 (SEQ ID NO:298) is shown in bold; this coding portion starts at position 319 and ends at position 3561. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P14 (SEQ ID NO:350) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
157 A -> G No
241 T -> A Yes
340 T -> G Yes
456 T -> G Yes
1993 G -> A Yes
2812 G -> T Yes
3274 C -> T Yes
3282 C -> T Yes
3501 A -> G Yes
3527 T -> C Yes

Variant protein HUMCA1XIA_P15 (SEQ ID NO:351) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T17 (SEQ ID NO:299). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:348)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMCA1XIA_P15 (SEQ ID NO:351) and CA1B_HUMAN (SEQ ID NO:348):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P15 (SEQ ID NO:351), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEK corresponding to amino acids 1-714 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-714 of HUMCA1XIA_P15 (SEQ ID NO:351 ), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCCNLSFGILIPLQK (SEQ ID NO:973) corresponding to amino acids 715-729 of HUMCA1XIA_P15 (SEQ ID NO:351) , wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCA1XIA_P15 (SEQ ID NO:351), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK (SEQ ID NO:973) in HUMCA1XIA_P15 (SEQ ID NO:351).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMCA1XIA_P15 (SEQ ID NO:351) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P15 (SEQ ID NO:351) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
8 W -> G Yes
46 D -> E Yes
559 G -> S Yes

The glycosylation sites of variant protein HUMCA1XIA_P15 (SEQ ID NO:351), as compared to the known protein Collagen alpha 1 (SEQ ID NO:348), are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 11
Glycosylation site(s)
Position(s) on known Present in
amino acid sequence variant protein?
1640 no

Variant protein HUMCA1XIA_P15 (SEQ ID NO:351) is encoded by the following transcript(s): HUMCA1XIA_T17 (SEQ ID NO:299), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T17 (SEQ ID NO:299) is shown in bold; this coding portion starts at position 319 and ends at position 2505. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P15 (SEQ ID NO:351) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
157 A -> G No
241 T -> A Yes
340 T -> G Yes
456 T -> G Yes
1993 G -> A Yes
2473 C -> T Yes

Variant protein HUMCA1XIA_P16 (SEQ ID NO:352) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T19 (SEQ ID NO:300). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:348)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMCA1XIA_P16 (SEQ ID NO:352) and CA1B_HUMAN (SEQ ID NO:348):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P16 (SEQ ID NO:352), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA corresponding to amino acids 1-648 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-648 of HUMCA1XIA_P16 (SEQ ID NO:352), a second amino acid sequence being at least 90% homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667-714 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID NO:352), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:974) corresponding to amino acids 697-738 of HUMCA1XIA_P16 (SEQ ID NO:352), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMCA1XIA_P16 (SEQ ID NO:352), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and ending at any of amino acid numbers 649+((n−2)−x), in which x varies from 0 to n−2.

3. An isolated polypeptide encoding for a tail of HUMCA1XIA_P16 (SEQ ID NO:352), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:974) in HUMCA1XIA_P16 (SEQ ID NO:352).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMCA1XIA_P16 (SEQ ID NO:352) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P16 (SEQ ID NO:352) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
8 W -> G Yes
46 D -> E Yes
559 G -> S Yes

The glycosylation sites of variant protein HUMCA1XIA_P16 (SEQ ID NO:352), as compared to the known protein Collagen alpha 1 (SEQ ID NO:348), are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 14
Glycosylation site(s)
Position(s) on known Present in
amino acid sequence variant protein?
1640 no

Variant protein HUMCA1XIA_P16 (SEQ ID NO:352) is encoded by the following transcript(s): HUMCA1XIA_T19 (SEQ ID NO:300), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T19 (SEQ ID NO:300) is shown in bold; this coding portion starts at position 319 and ends at position 2532. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P16 (SEQ ID NO:352) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
157 A -> G No
241 T -> A Yes
340 T -> G Yes
456 T -> G Yes
1993 G -> A Yes
2606 C -> A Yes
2677 T -> G Yes
2849 C -> T Yes

Variant protein HUMCA1XIA_P17 (SEQ ID NO:353) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T20 (SEQ ID NO:301). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:348)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMCA1XIA_P17 (SEQ ID NO:353) and CA1B_HUMAN (SEQ ID NO:348):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P17 (SEQ ID NO:353), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids 1-260 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-260 of HUMCA1XIA_P17 (SEQ ID NO:353), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSTRPEKVFVFQ (SEQ ID NO:975) corresponding to amino acids 261-273 of HUMCA1XIA_P17 (SEQ ID NO:353), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCA1XIA_P17 (SEQ ID NO:353), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSTRPEKVFVFQ (SEQ ID NO:975) in HUMCA1XIA_P17 (SEQ ID NO:353).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMCA1XIA_P17 (SEQ ID NO:353) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P17 (SEQ ID NO:353) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
8 W -> G Yes
46 D -> E Yes

The glycosylation sites of variant protein HUMCA1XIA_P17 (SEQ ID NO:353), as compared to the known protein Collagen alpha 1 (SEQ ID NO:348), are described in Table 17 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 17
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
1640 no

Variant protein HUMCA1XIA_P17 (SEQ ID NO:353) is encoded by the following transcript(s): HUMCA XIA_T20 (SEQ ID NO:301), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T20 (SEQ ID NO:301) is shown in bold; this coding portion starts at position 319 and ends at position 1137. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P17 (SEQ ID NO:353) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
157 A -> G No
241 T -> A Yes
340 T -> G Yes
456 T -> G Yes
1150 A -> C Yes

As noted above, cluster HUMCA1XIA features 46 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMCA1XIA_node—0 (SEQ ID NO:302) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299), HUMCA1XIA_T19 (SEQ ID NO:300) and HUMCA1XIA_T20 (SEQ ID NO:301 ). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1 424
HUMCA1XIA_T17 (SEQ ID NO:299) 1 424
HUMCA1XIA_T19 (SEQ ID NO:300) 1 424
HUMCA1XIA_T20 (SEQ ID NO:301) 1 424

Segment cluster HUMCA1XIA_node—2 (SEQ ID NO:303) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299), HUMCA1XIA_T19 (SEQ ID NO:300) and HUMCA1XIA_T20 (SEQ ID NO:301). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 425 592
HUMCA1XIA_T17 (SEQ ID NO:299) 425 592
HUMCA1XIA_T19 (SEQ ID NO:300) 425 592
HUMCA1XIA_T20 (SEQ ID NO:301) 425 592

Segment cluster HUMCA1XIA_node—4 (SEQ ID NO:304) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299), HUMCA1XIA_T19 (SEQ ID NO:300) and HUMCA1XIA_T20 (SEQ ID NO:301). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 593 806
HUMCA1XIA_T17 (SEQ ID NO:299) 593 806
HUMCA1XIA_T19 (SEQ ID NO:300) 593 806
HUMCA1XIA_T20 (SEQ ID NO:301) 593 806

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 22.

TABLE 22
Oligonucleotides related to this segment
Overexpressed Chip
Oligonucleotide name in cancers reference
HUMCA1XIA_0_18_0 breast malignant BRS
(SEQ ID NO:904) tumors

Segment cluster HUMCA1XIA_node—6 (SEQ ID NO:305) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299), HUMCA1XIA_T19 (SEQ ID NO:300) and HUMCA1XIA_T20 (SEQ ID NO:301). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 807 969
HUMCA1XIA_T17 (SEQ ID NO:299) 807 969
HUMCA1XIA_T19 (SEQ ID NO:300) 807 969
HUMCA1XIA_T20 (SEQ ID NO:301) 807 969

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 24.

TABLE 24
Oligonucleotides related to this segment
Overexpressed Chip
Oligonucleotide name in cancers reference
HUMCA1XIA_0_18_0 breast malignant BRS
(SEQ ID NO:904) tumors

Segment cluster HUMCA1XIA_node—8 (SEQ ID NO:306) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299), HUMCA1XIA_T19 (SEQ ID NO:300) and HUMCA1XIA_T20 (SEQ ID NO:301). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 970 1098
HUMCA1XIA_T17 (SEQ ID NO:299) 970 1098
HUMCA1XIA_T19 (SEQ ID NO:300) 970 1098
HUMCA1XIA_T20 (SEQ ID NO:301) 970 1098

Segment cluster HUMCA1XIA_node—9 (SEQ ID NO:307) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T20 (SEQ ID NO:301). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T20 (SEQ ID NO:301) 1099 1271

Segment cluster HUMCA1XIA_node—18 (SEQ ID NO:308) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1309 1522
HUMCA1XIA_T17 (SEQ ID NO:299) 1309 1522
HUMCA1XIA_T19 (SEQ ID NO:300) 1309 1522

Segment cluster HUMCA1XIA_node—54 (SEQ ID NO:309) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T19 (SEQ ID NO:300). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T19 (SEQ ID NO:300) 2407 2836

Segment cluster HUMCA1XIA_node—55 (SEQ ID NO:310) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T17 (SEQ ID NO 299) 2461 2648
HUMCA1XIA_T19 (SEQ ID NO 300) 2837 3475

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 30.

TABLE 30
Oligonucleotides related to this segment
Overexpressed Chip
Oligonucleotide name in cancers reference
HUMCA1XIA_0_0_14909 breast malignant BRS
(SEQ ID NO:903) tumors

Segment cluster HUMCA1XIA_node—92 (SEQ ID NO:311) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 3487 3615

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HUMCA1XIA_node—11 (SEQ ID NO:312) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1099 1215
HUMCA1XIA_T17 (SEQ ID NO:299) 1099 1215
HUMCA1XIA_T19 (SEQ ID NO:300) 1099 1215

Segment cluster HUMCA1XIA_node—15 (SEQ ID NO:313) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1216 1308
HUMCA1XIA_T17 (SEQ ID NO:299) 1216 1308
HUMCA1XIA_T19 (SEQ ID NO:300) 1216 1308

Segment cluster HUMCA1XIA_node—19 (SEQ ID NO:314) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1523 1563
HUMCA1XIA_T17 (SEQ ID NO:299) 1523 1563
HUMCA1XIA_T19 (SEQ ID NO:300) 1523 1563

Segment cluster HUMCA1XIA_node—21 (SEQ ID NO:315) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1564 1626
HUMCA1XIA_T17 (SEQ ID NO:299) 1564 1626
HUMCA1XIA_T19 (SEQ ID NO:300) 1564 1626

Segment cluster HUMCA1XIA_node—23 (SEQ ID NO:316) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1627 1668
HUMCA1XIA_T17 (SEQ ID NO:299) 1627 1668
HUMCA1XIA_T19 (SEQ ID NO:300) 1627 1668

Segment cluster HUMCA1XIA_node—25 (SEQ ID NO:317) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1669 1731
HUMCA1XIA_T17 (SEQ ID NO:299) 1669 1731
HUMCA1XIA_T19 (SEQ ID NO:300) 1669 1731

Segment cluster HUMCA1XIA_node—27 (SEQ ID NO:318) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1732 1806
HUMCA1XIA_T17 (SEQ ID NO:299) 1732 1806
HUMCA1XIA_T19 (SEQ ID NO:300) 1732 1806

Segment cluster HUMCA1XIA_node—29 (SEQ ID NO:319) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1807 1890
HUMCA1XIA_T17 (SEQ ID NO:299) 1807 1890
HUMCA1XIA_T19 (SEQ ID NO:300) 1807 1890

Segment cluster HUMCA1XIA_node—31 (SEQ ID NO:320) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1891 1947
HUMCA1XIA_T17 (SEQ ID NO:299) 1891 1947
HUMCA1XIA_T19 (SEQ ID NO:300) 1891 1947

Segment cluster HUMCA1XIA_node—33 (SEQ ID NO:321) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 1948 2001
HUMCA1XIA_T17 (SEQ ID NO:299) 1948 2001
HUMCA1XIA_T19 (SEQ ID NO:300) 1948 2001

Segment cluster HUMCA1XIA_node—35 (SEQ ID NO:322) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2002 2055
HUMCA1XIA_T17 (SEQ ID NO:299) 2002 2055
HUMCA1XIA_T19 (SEQ ID NO:300) 2002 2055

Segment cluster HUMCA1XIA_node—37 (SEQ ID NO:323) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2056 2109
HUMCA1XIA_T17 (SEQ ID NO:299) 2056 2109
HUMCA1XIA_T19 (SEQ ID NO:300) 2056 2109

Segment cluster HUMCA1XIA_node—39 (SEQ ID NO:324) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2110 2163
HUMCA1XIA_T17 (SEQ ID NO:299) 2110 2163
HUMCA1XIA_T19 (SEQ ID NO:300) 2110 2163

Segment cluster HUMCA1XIA_node—41 (SEQ ID NO:325) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2164 2217
HUMCA1XIA_T17 (SEQ ID NO:299) 2164 2217
HUMCA1XIA_T19 (SEQ ID NO:300) 2164 2217

Segment cluster HUMCA1XIA_node—43 (SEQ ID NO:326) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCAIXIA_T16 (SEQ ID NO:298) 2218 2262
HUMCA1XIA_T17 (SEQ ID NO:299) 2218 2262
HUMCA1XIA_T19 (SEQ ID NO:300) 2218 2262

Segment cluster HUMCA1XIA_node—45 (SEQ ID NO:327) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298) and HUMCA1XIA_T17 (SEQ ID NO:299). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2263 2316
HUMCA1XIA_T17 (SEQ ID NO:299) 2263 2316

Segment cluster HUMCA1XIA_node—47 (SEQ ID NO:328) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298, HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2317 2361
HUMCA1XIA_T17 (SEQ ID NO:299) 2317 2361
HUMCA1XIA_T19 (SEQ ID NO:300) 2263 2307

Segment cluster HUMCA1XIA_node—49 (SEQ ID NO:329) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2362 2415
HUMCA1XIA_T17 (SEQ ID NO:299) 2362 2415
HUMCA1XIA_T19 (SEQ ID NO:300) 2308 2361

Segment cluster HUMCA1XIA_node—51 (SEQ ID NO:330) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298), HUMCA1XIA_T17 (SEQ ID NO:299) and HUMCA1XIA_T19 (SEQ ID NO:300). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2416 2460
HUMCA1XIA_T17 (SEQ ID NO:299) 2416 2460
HUMCA1XIA_T19 (SEQ ID NO:300) 2362 2406

Segment cluster HUMCA1XIA_node—57 (SEQ ID NO:331) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2461 2514

Segment cluster HUMCA1XIA_node—59 (SEQ ID NO:332) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2515 2559

Segment cluster HUMCA1XIA_node—62 (SEQ ID NO:333) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2560 2613

Segment cluster HUMCA1XIA_node—64 (SEQ ID NO:334) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2614 2658

Segment cluster HUMCA1XIA_node—66 (SEQ ID NO:335) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HUMCA1XIA_T16 (SEQ ID NO:298) 2659 2712

Segment cluster HUMCA1XIA_node—68 (SEQ ID NO:336) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 2713 2820

Segment cluster HUMCA1XIA_node—70 (SEQ ID NO:337) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 2821 2874

Segment cluster HUMCA1XIA_node—72 (SEQ ID NO:338) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 2875 2928

Segment cluster HUMCA1XIA_node—74 (SEQ ID NO:339) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 2929 2973

Segment cluster HUMCA1XIA_node—76 (SEQ ID NO:340) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 2974 3027

Segment cluster HUMCA1XIA_node—78 (SEQ ID NO:341) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3028 3072

Segment cluster HUMCA1XIA_node—81 (SEQ ID NO:342) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3073 3126

Segment cluster HUMCA1XIA_node—83 (SEQ ID NO:343) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3127 3180

Segment cluster HUMCA1XIA_node—85 (SEQ ID NO:344) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3181 3234

Segment cluster HUMCA1XIA_node—87 (SEQ ID NO:345) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3235 3342

Segment cluster HUMCA1XIA_node—89 (SEQ ID NO:346) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3343 3432

Segment cluster HUMCA1XIA_node—91 (SEQ ID NO:347) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:298). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMCA1XIA_T16 (SEQ ID NO:298) 3433 3486

Transcript nucleic acid sequences:

Variant protein alignment to the previously known protein:

Sequence name: CA1B_HUMAN_V5 (SEQ ID NO:349)

Sequence documentation:

Alignment of: HUMCA1XIA_P14 (SEQ ID NO:350)×CA1B_HUMAN_V5 (SEQ ID NO:349).

Alignment segment 1/1:

Quality: 10456.00
Escore: 0
Matching length: 1058 Total length: 1058
Matching Percent 99.91 Matching Percent 99.91
Similarity: Identity:
Total Percent Similarity: 99.91 Total Percent Identity: 99.91
Gaps: 0

Alignment:

         .         .         .         .         .
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
         .         .         .         .         .
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
         .         .         .         .         .
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
         .         .         .         .         .
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
         .         .         .         .         .
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
         .         .         .         .         .
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
         .         .         .         .         .
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
         .         .         .         .         .
351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400
         .         .         .         .         .
401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450
         .         .         .         .         .
451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500
         .         .         .         .         .
501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550
         .         .         .         .         .
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600
         .         .         .         .         .
601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650
         .         .         .         .         .
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
         .         .         .         .         .
701 LPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 LPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750
         .         .         .         .         .
751 GPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 GPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800
         .         .         .         .         .
801 VGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQG 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 VGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQG 850
         .         .         .         .         .
851 PKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKP 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 PKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKP 900
         .         .         .         .         .
901 GPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQ 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 GPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQ 950
         .         .         .         .         .
951 RGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQGLPG 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 RGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQGLPG 1000
         .         .         .         .         .
1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050
1051 GPPGPVVS 1058
|||||| |
1051 GPPGPVGS 1058

Sequence name: CA1B_HUMAN (SEQ ID NO:348)

Sequence documentation:

Alignment of: HUMCA1XIA_P15 (SEQ ID NO:351)×CA1B_HUMAN (SEQ ID NO:348).

Alignment segment 1/1:

Quality: 7073.00
Escore: 0
Matching length: 714 Total length: 714
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
         .         .         .         .         .
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
         .         .         .         .         .
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
         .         .         .         .         .
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
         .         .         .         .         .
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
         .         .         .         .         .
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
         .         .         .         .         .
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
         .         .         .         .         .
351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400
         .         .         .         .         .
401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450
         .         .         .         .         .
451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500
         .         .         .         .         .
501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550
         .         .         .         .         .
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600
         .         .         .         .         .
601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650
         .         .         .         .         .
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
         .
701 LPGPQGPIGPPGEK 714
||||||||||||||
701 LPGPQGPIGPPGEK 714

Sequence name: CA1B_HUMAN (SEQ ID NO:348)

Sequence documentation:

Alignment of: HUMCA1XIA_P16 (SEQ ID NO:352)×CA1B_HUMAN (SEQ ID NO:348).

Alignment segment 1/1:

Quality: 6795.00
Escore: 0
Matching length: 696 Total length: 714
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 97.48 Total Percent Identity: 97.48
Gaps: 1

Alignment:

         .         .         .         .         .
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
         .         .         .         .         .
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
         .         .         .         .         .
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
         .         .         .         .         .
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
         .         .         .         .         .
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
         .         .         .         .         .
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300
         .         .         .         .         .
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350
         .         .         .         .         .
351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400
         .         .         .         .         .
401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450
         .         .         .         .         .
451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500
         .         .         .         .         .
501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550
         .         .         .         .         .
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600
         .         .         .         .         .
601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA.. 648
||||||||||||||||||||||||||||||||||||||||||||||||
601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650
         .         .         .         .         .
649 ................GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 682
                ||||||||||||||||||||||||||||||||||
651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700
         .
683 LPGPQGPIGPPGEK 696
||||||||||||||
701 LPGPQGPIGPPGEK 714

Sequence name: CA1B_HUMAN (SEQ ID NO:348)

Sequence documentation:

Alignment of: HUMCA1XIA_P17 (SEQ ID NO:353)×CA1B HUMAN (SEQ ID NO:348).

Alignment segment 1/1:

Quality: 2561.00
Escore: 0
Matching length: 260 Total length: 260
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50
         .         .         .         .         .
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100
         .         .         .         .         .
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150
         .         .         .         .         .
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200
         .         .         .         .         .
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250
         .
251 AQAQEPQIDE 260
||||||||||
251 AQAQEPQIDE 260

Description for Cluster R20779

Cluster R20779 features 1 transcript(s) and 24 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
R20779_T7 354

TABLE 2
Segments of interest
Segment Name Sequence ID No.
R20779_node_0 355
R20779_node_2 356
R20779_node_7 357
R20779_node_9 358
R20779_node_18 359
R20779_node_21 360
R20779_node_24 361
R20779_node_27 362
R20779_node_28 363
R20779_node_30 364
R20779_node_31 365
R20779_node_32 366
R20779_node_1 367
R20779_node_3 368
R20779_node_10 369
R20779_node_11 370
R20779_node_14 371
R20779_node_17 372
R20779_node_19 373
R20779_node_20 374
R20779_node_22 375
R20779_node_23 376
R20779_node_25 377
R20779_node_29 378

TABLE 3
Proteins of interest
Protein Name Sequence ID No. Corresponding Transcript(s)
R20779_P2 380 R20779_T7 (SEQ ID
NO: 354)

These sequences are variants of the known protein Stanniocalcin 2 precursor (SEQ ID NO:379) (SwissProt accession identifier STC2_HUMAN; known also according to the synonyms STC-2; Stanniocalcin-related protein; STCRP; STC-related protein), SEQ ID NO: 379, referred to herein as the previously known protein.

Protein Stanniocalcin 2 precursor (SEQ ID NO:379) is known or believed to have the following function(s): Has an anti-hypocalcemic action on calcium and phosphate homeostasis. The sequence for protein Stanniocalcin 2 precursor (SEQ ID NO:379) is given at the end of the application, as “Stanniocalcin 2 precursor (SEQ ID NO:379) amino acid sequence”. Protein Stanniocalcin 2 precursor (SEQ ID NO:379) localization is believed to be Secreted (Potential).

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cell surface receptor linked signal transduction; cell-cell signaling; nutritional response pathway, which are annotation(s) related to Biological Process; hormone, which are annotation(s) related to Molecular Function; and extracellular, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster R20779 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 33 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 33 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

TABLE 4
Normal tissue distribution
Name of Tissue Number
Bone 825
Brain 0
Colon 0
epithelial 32
general 38
kidney 22
Liver 9
Lung 11
Lymph nodes 0
Breast 215
muscle 35
Ovary 36
pancreas 4
prostate 80
Skin 99
stomach 0
Uterus 4

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
Bone 5.9e−01 7.4e−01 1 0.2 1 0.1
Brain 2.5e−02 1.6e−02 2.2e−01 6.0 3.5e−02 8.0
Colon 1.7e−01 1.7e−01 1 1.3 7.7e−01 1.5
epithelial 1.7e−01 1.5e−03 5.9e−01 1.0 2.0e−04 2.0
general 2.4e−02 6.2e−07 7.6e−01 0.8 4.6e−05 1.6
kidney 4.3e−01 2.7e−01 6.2e−01 1.3 1.5e−01 2.0
Liver 8.3e−01 7.6e−01 1 0.8 3.3e−01 1.6
Lung 1.2e−01 1.4e−03 1.9e−01 2.9 1.6e−05 7.7
Lymph nodes 1 3.1e−01 1 1.0 1 1.4
Breast 6.8e−01 6.8e−01 6.9e−01 0.8 3.6e−01 0.8
muscle 9.2e−01 4.8e−01 1 0.3 1.4e−03 1.4
Ovary 8.4e−01 7.1e−01 9.0e−01 0.7 8.6e−01 0.8
pancreas 9.3e−01 6.8e−01 1 0.7 1.5e−01 2.0
prostate 9.1e−01 5.0e−01 9.8e−01 0.4 5.7e−01 0.7
Skin 6.3e−01 7.5e−01 7.1e−01 0.8 9.5e−01 0.3
stomach 1 4.5e−01 1 1.0 5.1e−01 1.8
Uterus 7.1e−01 2.6e−01 4.4e−01 1.7 4.1e−01 1.8

For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously described. The following oligonucleotides were found to hit this cluster but not other segments/transcripts below, shown in Table 6.

TABLE 6
Oligonucleotides related to this cluster
Oligonucleotide name Overexpressed in cancers Chip reference
R20779_0_0_30670 (SEQ breast malignant tumors BRS
ID NO: 905)

As noted above, cluster R20779 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Stanniocalcin 2 precursor (SEQ ID NO:379). A description of each variant protein according to the present invention is now provided.

Variant protein R20779_P2 (SEQ ID NO:380) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R20779_T7 (SEQ ID NO:354). An alignment is given to the known protein (Stanniocalcin 2 precursor (SEQ ID NO:379)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between R20779_P2 (SEQ ID NO:380) and STC2_HUMAN (SEQ ID NO:379):

1. An isolated chimeric polypeptide encoding for R20779_P2 (SEQ ID NO:380), comprising a first amino acid sequence being at least 90% homologous to MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLV NAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRH RFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids 1-169 of STC2_HUMAN (SEQ ID NO:379), which also corresponds to amino acids 1-169 of R20779_P2 (SEQ ID NO:380), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:976) corresponding to amino acids 170-187 of R20779_P2 (SEQ ID NO:380) , wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R20779_P2 (SEQ ID NO:380), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:976) in R20779_P2 (SEQ ID NO:380).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R20779_P2 (SEQ ID NO:380) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R20779_P2 (SEQ ID NO:380) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
16 L -> No
98 Q -> No
171 Y -> C Yes
177 M -> V Yes

The glycosylation sites of variant protein R20779_P2 (SEQ ID NO:380), as compared to the known protein Stanniocalcin 2 precursor (SEQ ID NO:379), are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 8
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
73 yes 73

Variant protein R20779_P2 (SEQ ID NO:380) is encoded by the following transcript(s): R20779_T7 (SEQ ID NO:354), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R20779_T7 (SEQ ID NO:354) is shown in bold; this coding portion starts at position 1397 and ends at position 1957. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R20779_P2 (SEQ ID NO:380) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
1442 T -> No
1690 G -> No
1732 C -> T Yes
1867 G -> T Yes
1908 A -> G Yes
1925 A -> G Yes
1968 G -> A Yes
2087 C -> T No
2138 C -> T Yes
2270 C -> No
2443 A -> No
2478 G -> No
2479 C -> A No
2616 C -> A No
2941 C -> No
3196 -> A No
3479 T -> G Yes
4290 C -> T Yes
4358 G -> A Yes
5363 G -> A No

As noted above, cluster R20779 features 24 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster R20779_node—0 (SEQ ID NO:355) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1 1298

Segment cluster R20779_node—2 (SEQ ID NO:356) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1337 1506

Segment cluster R20779_node—7 (SEQ ID NO:357) according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1548 1690

Segment cluster R20779_node—9 (SEQ ID NO:358) according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1691 1838

Segment cluster R20779_node—18 (SEQ ID NO:359) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2009 2176

Segment cluster R20779_node—21 (SEQ ID NO:360) according to the present invention is supported by 106 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2219 2796

Segment cluster R20779_node—24 (SEQ ID NO:361) according to the present invention is supported by 100 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2977 3667

Segment cluster R20779_node—27 (SEQ ID NO:362) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 3673 3803

Segment cluster R20779_node—28 (SEQ ID NO:363) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 3804 4050

Segment cluster R20779_node—30 (SEQ ID NO:364) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 4068 4193

Segment cluster R20779_node—31 (SEQ ID NO:365) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 4194 4424

Segment cluster R20779_node—32 (SEQ ID NO:366) according to the present invention is supported by 88 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 4425 5503

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster R20779_node—1 (SEQ ID NO:367) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1299 1336

Segment cluster R20779_node—3 (SEQ ID NO:368) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1507 1547

Segment cluster R20779_node—10 (SEQ ID NO:369) according to the present invention can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1839 1849

Segment cluster R20779_node—11 (SEQ ID NO:370) according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1850 1902

Segment cluster R20779_node—14 (SEQ ID NO:371) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1903 1975

Segment cluster R20779_node—17 (SEQ ID NO:372) according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 1976 2008

Segment cluster R20779_node—19 (SEQ ID NO:373) according to the present invention can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2177 2188

Segment cluster R20779_node—20 (SEQ ID NO:374) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2189 2218

Segment cluster R20779_node—22 (SEQ ID NO:375) according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2797 2899

Segment cluster R20779_node—23 (SEQ ID NO:376) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 2900 2976

Segment cluster R20779_node—25 (SEQ ID NO:377) according to the present invention can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 3668 3672

Segment cluster R20779_node—29 (SEQ ID NO:378) according to the present invention can be found in the following transcript(s): R20779_T7 (SEQ ID NO:354). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R20779_T7 (SEQ ID NO: 354) 4051 4067

Variant protein alignment to the previously known protein:

Sequence name: STC2_HUMAN (SEQ ID NO:379)

Sequence documentation:

Alignment of: R20779_P2 (SEQ ID NO:380)×STC213 HUMAN (SEQ ID NO:379).

Alignment segment 1/1:

Quality: 1688.00
Escore: 0
Matching length: 171 Total length: 171
Matching Percent 99.42 Matching Percent 99.42
Similarity: Identity:
Total Percent 99.42 Total Percent 99.42
Similarity: Identity:
Gaps: 0

Alignment:

         .         .         .         .         .
1 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNT 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNT 50
         .         .         .         .         .
51 AEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGK 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AEIQHCLVNAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGK 100
         .         .         .         .         .
101 SFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQ 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 SFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQ 150
         .         .
151 ENTRVIVEMIHFKDLLLHECY 171
|||||||||||||||||||||
151 ENTRVIVEMIHFKDLLLHEPY 171

Description for Cluster HSS100PCB

Cluster HSS100PCB features 1 transcript(s) and 3 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HSS100PCB_T1 381

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HSS100PCB_node_3 382
HSS100PCB_node_4 383
HSS100PCB_node_5 384

TABLE 3
Proteins of interest
Protein Name Sequence ID No. Corresponding Transcript(s)
HSS100PCB_P3 386 HSS100PCB_T1 (SEQ ID
NO: 381)

These sequences are variants of the known protein S-100P protein (SEQ ID NO:385) (SwissProt accession identifier S10P_HUMAN), SEQ ID NO: 385, referred to herein as the previously known protein.

The sequence for protein S-100P protein (SEQ ID NO:385) is given at the end of the application, as “S-100P protein (SEQ ID NO:385) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
32 E -> T
44 F -> E

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: calcium binding; protein binding, which are annotation(s) related to Molecular Function.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HSS100PCB can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 34 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 34 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues.

TABLE 5
Normal tissue distribution
Name of Tissue Number
Bladder 41
Colon 37
Epithelial 38
General 22
Kidney 0
Liver 0
Lung 18
Breast 0
bone marrow 0
Ovary 0
pancreas 0
prostate 46
stomach 553
Uterus 13

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
bladder 3.3e−01 2.9e−01 2.9e−02 2.8 3.5e−02 2.8
Colon 3.0e−01 1.9e−01 5.2e−01 1.2 2.4e−01 1.7
epithelial 4.7e−02 1.6e−02 2.0e−01 1.2 6.1e−02 1.3
general 1.1e−03 6.8e−05 1.4e−02 1.5 4.9e−04 1.7
kidney 6.5e−01 7.2e−01 5.8e−01 1.7 7.0e−01 1.4
Liver 9.1e−01 4.9e−01 1 1.0 7.7e−02 2.1
Lung 6.8e−01 7.3e−01 2.2e−02 2.9 1.3e−01 1.7
Breast 2.8e−01 3.2e−01 4.7e−01 2.0 6.8e−01 1.5
bone marrow 1 6.7e−01 1 1.0 2.8e−01 2.8
Ovary 2.6e−01 3.0e−01 4.7e−01 2.0 5.9e−01 1.7
pancreas 3.3e−01 4.4e−01 7.6e−02 3.7 1.5e−01 2.8
prostate 9.1e−01 9.3e−01 5.8e−01 0.6 7.6e−01 0.5
stomach 3.7e−01 3.2e−01 1 0.1 1 0.3
Uterus 9.4e−01 7.0e−01 1 0.6 4.1e−01 1.1

As noted above, cluster HSS100PCB features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein S-100P protein (SEQ ID NO:385). A description of each variant protein according to the present invention is now provided.

Variant protein HSS100PCB_P3 (SEQ ID NO:386) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSS100PCB_T1 (SEQ ID NO:381). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSS100PCB_P3 (SEQ ID NO:386) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCB_P3 (SEQ ID NO:386) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
1 M -> R Yes
11 M -> L Yes
20 L -> F Yes

Variant protein HSS100PCB_P3 (SEQ ID NO:386) is encoded by the following transcript(s): HSS100PCB_T1 (SEQ ID NO:381), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSS100PCB_T1 (SEQ ID NO:381) is shown in bold; this coding portion starts at position 1057 and ends at position 1533. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCB_P3 (SEQ ID NO:386) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
52 C -> T Yes
107 A -> C Yes
458 C -> T Yes
468 A -> G Yes
648 C -> T Yes
846 C -> G Yes
882 G -> A Yes
960 C -> T No
965 C -> T Yes
1058 T -> G Yes
1087 A -> C Yes
1114 C -> T Yes
1968 G -> A Yes
1971 C -> T Yes
2010 C -> A Yes
2099 G -> No

As noted above, cluster HSS100PCB features 3 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSS100PCB_node—3 (SEQ ID NO:382) according to the present invention is supported by 16 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1 (SEQ ID NO:381). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSS100PCB_T1 (SEQ ID NO: 381) 1 1133

Segment cluster HSS100PCB_node—4 (SEQ ID NO:383) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1 (SEQ ID NO:381). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSS100PCB_T1 (SEQ ID NO: 381) 1134 1923

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 11.

TABLE 11
Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
HSS100PCB_0_0_12280 breast malignant tumors BRS
(SEQ ID NO: 906)

Segment cluster HSS100PCB_node—5 (SEQ ID NO:384) according to the present invention is supported by 141 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1 (SEQ ID NO:381). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSS100PCB_T1 (SEQ ID NO: 381) 1924 2201

Description for Cluster HSCOC4

Cluster HSCOC4 features 19 transcript(s) and 79 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HSCOC4_PEA_1_T1 387
HSCOC4_PEA_1_T2 388
HSCOC4_PEA_1_T3 389
HSCOC4_PEA_1_T4 390
HSCOC4_PEA_1_T5 391
HSCOC4_PEA_1_T7 392
HSCOC4_PEA_1_T8 393
HSCOC4_PEA_1_T11 394
HSCOC4_PEA_1_T12 395
HSCOC4_PEA_1_T14 396
HSCOC4_PEA_1_T15 397
HSCOC4_PEA_1_T20 398
HSCOC4_PEA_1_T21 399
HSCOC4_PEA_1_T25 400
HSCOC4_PEA_1_T28 401
HSCOC4_PEA_1_T30 402
HSCOC4_PEA_1_T31 403
HSCOC4_PEA_1_T32 404
HSCOC4_PEA_1_T40 405

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HSCOC4_PEA_1_node_1 406
HSCOC4_PEA_1_node_5 407
HSCOC4_PEA_1_node_7 408
HSCOC4_PEA_1_node_30 409
HSCOC4_PEA_1_node_33 410
HSCOC4_PEA_1_node_35 411
HSCOC4_PEA_1_node_37 412
HSCOC4_PEA_1_node_39 413
HSCOC4_PEA_1_node_43 414
HSCOC4_PEA_1_node_48 415
HSCOC4_PEA_1_node_49 416
HSCOC4_PEA_1_node_51 417
HSCOC4_PEA_1_node_58 418
HSCOC4_PEA_1_node_59 419
HSCOC4_PEA_1_node_62 420
HSCOC4_PEA_1_node_66 421
HSCOC4_PEA_1_node_72 422
HSCOC4_PEA_1_node_77 423
HSCOC4_PEA_1_node_79 424
HSCOC4_PEA_1_node_93 425
HSCOC4_PEA_1_node_100 426
HSCOC4_PEA_1_node_105 427
HSCOC4_PEA_1_node_107 428
HSCOC4_PEA_1_node_108 429
HSCOC4_PEA_1_node_109 430
HSCOC4_PEA_1_node_110 431
HSCOC4_PEA_1_node_112 432
HSCOC4_PEA_1_node_113 433
HSCOC4_PEA_1_node_2 434
HSCOC4_PEA_1_node_8 435
HSCOC4_PEA_1_node_10 436
HSCOC4_PEA_1_node_12 437
HSCOC4_PEA_1_node_14 438
HSCOC4_PEA_1_node_17 439
HSCOC4_PEA_1_node_19 440
HSCOC4_PEA_1_node_21 441
HSCOC4_PEA_1_node_22 442
HSCOC4_PEA_1_node_28 443
HSCOC4_PEA_1_node_29 444
HSCOC4_PEA_1_node_41 445
HSCOC4_PEA_1_node_45 446
HSCOC4_PEA_1_node_47 447
HSCOC4_PEA_1_node_50 448
HSCOC4_PEA_1_node_53 449
HSCOC4_PEA_1_node_55 450
HSCOC4_PEA_1_node_57 451
HSCOC4_PEA_1_node_60 452
HSCOC4_PEA_1_node_64 453
HSCOC4_PEA_1_node_69 454
HSCOC4_PEA_1_node_70 455
HSCOC4_PEA_1_node_71 456
HSCOC4_PEA_1_node_73 457
HSCOC4_PEA_1_node_74 458
HSCOC4_PEA_1_node_75 459
HSCOC4_PEA_1_node_76 460
HSCOC4_PEA_1_node_78 461
HSCOC4_PEA_1_node_80 462
HSCOC4_PEA_1_node_82 463
HSCOC4_PEA_1_node_83 464
HSCOC4_PEA_1_node_84 465
HSCOC4_PEA_1_node_85 466
HSCOC4_PEA_1_node_86 467
HSCOC4_PEA_1_node_87 468
HSCOC4_PEA_1_node_88 469
HSCOC4_PEA_1_node_89 470
HSCOC4_PEA_1_node_90 471
HSCOC4_PEA_1_node_91 472
HSCOC4_PEA_1_node_92 473
HSCOC4_PEA_1_node_94 474
HSCOC4_PEA_1_node_96 475
HSCOC4_PEA_1_node_97 476
HSCOC4_PEA_1_node_98 477
HSCOC4_PEA_1_node_99 478
HSCOC4_PEA_1_node_101 479
HSCOC4_PEA_1_node_102 480
HSCOC4_PEA_1_node_103 481
HSCOC4_PEA_1_node_104 482
HSCOC4_PEA_1_node_106 483
HSCOC4_PEA_1_node_111 484

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
HSCOC4_PEA_1_P3 488 HSCOC4_PEA_1_T1 (SEQ
ID NO: 387)
HSCOC4_PEA_1_P5 489 HSCOC4_PEA_1_T3 (SEQ
ID NO: 389)
HSCOC4_PEA_1_P6 490 HSCOC4_PEA_1_T4 (SEQ
ID NO: 390)
HSCOC4_PEA_1_P12 491 HSCOC4_PEA_1_T11 (SEQ
ID NO: 394)
HSCOC4_PEA_1_P15 492 HSCOC4_PEA_1_T14 (SEQ
ID NO: 396)
HSCOC4_PEA_1_P16 493 HSCOC4_PEA_1_T15 (SEQ
ID NO: 397)
HSCOC4_PEA_1_P20 494 HSCOC4_PEA_1_T20 (SEQ
ID NO: 398)
HSCOC4_PEA_1_P9 495 HSCOC4_PEA_1_T21 (SEQ
ID NO: 399)
HSCOC4_PEA_1_P22 496 HSCOC4_PEA_1_T25 (SEQ
ID NO: 400)
HSCOC4_PEA_1_P23 497 HSCOC4_PEA_1_T28 (SEQ
ID NO: 401)
HSCOC4_PEA_1_P24 498 HSCOC4_PEA_1_T30 (SEQ
ID NO: 402)
HSCOC4_PEA_1_P25 499 HSCOC4_PEA_1_T31 (SEQ
ID NO: 403)
HSCOC4_PEA_1_P26 500 HSCOC4_PEA_1_T32 (SEQ
ID NO: 404)
HSCOC4_PEA_1_P30 501 HSCOC4_PEA_1_T40 (SEQ
ID NO: 405)
HSCOC4_PEA_1_P38 502 HSCOC4_PEA_1_T2 (SEQ
ID NO: 388)
HSCOC4_PEA_1_P39 503 HSCOC4_PEA_1_T5 (SEQ
ID NO: 391)
HSCOC4_PEA_1_P40 504 HSCOC4_PEA_1_T7 (SEQ
ID NO: 392)
HSCOC4_PEA_1_P41 505 HSCOC4_PEA_1_T8 (SEQ
ID NO: 393)
HSCOC4_PEA_1_P42 506 HSCOC4_PEA_1_T12 (SEQ
ID NO: 395)

These sequences are variants of the known protein Complement C4 precursor [Contains: C4a anaphylatoxin] (SwissProt accession identifier CO4_HUMAN) SEQ ID NO: 485), referred to herein as the previously known protein.

Protein Complement C4 precursor [Contains: C4a anaphylatoxin] (SEQ ID NO:485) is known or believed to have the following function(s): C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. The sequence for protein Complement C4 precursor [Contains: C4a anaphylatoxin] (SEQ ID NO:485) is given at the end of the application, as “Complement C4 precursor [Contains: C4a anaphylatoxin] (SEQ ID NO:485) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s)
onamino acid
sequence Comment
 477 R -> W (in allotype C4A6). /FTId = VAR_001987.
 726 P -> L (in allotype C4A3). /FTId = VAR_001988.
1073 D -> G (in allotype C4A1, allotype C4B1 and allotype
C4B3). /FTId = VAR_001989.
1120-1125 PCPVLD -> LSPVIH (in allotype C4B).
/FTId = VAR_001990.
1176 N -> S (in allotype C4A1, allotype C4B1, allotype C4B3
and allotype C4B5). /FTId = VAR_001991.
1201 S -> T (in allotype C4A6, allotype C4A3, allotype C4A1
and allotype C4B). /FTId = VAR_001992.
1207 V -> A (in allotype C4A1, allotype C4B1, allotype C4B2
and allotype C4B3). /FTId = VAR_001993.
1210 L -> R (in allotype C4A1, allotype C4B1, allotype C4B2
and allotype C4B3). /FTId = VAR_001994.
1286 S -> A (in allotype C4A6, allotype C4A1, allotype
C4A3A and allotype C4B). /FTId = VAR_001995.
 1-12 MRLLWGLIWASS -> PREVRSVCLSAT
 347 S -> Y
 418 V -> A
 727 D -> N
 907 A -> T
980-981 VT -> LQ
1013 Q -> E
1317 I -> F
1418-1420 Missing
1654 T -> RA
1698 H -> Q

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: muscle contraction regulation; inflammatory response; complement activation; complement activation, classical pathway, which are annotation(s) related to Biological Process; complement component; proteinase inhibitor, which are annotation(s) related to Molecular Function; and extracellular; extracellular space, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HSCOC4 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 35 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 35 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

TABLE 5
Normal tissue distribution
Name of Tissue Number
adrenal 853
bladder 328
bone 6
brain 111
colon 245
epithelial 264
general 163
head and neck 0
kidney 141
liver 4109
lung 64
lymph nodes 120
breast 96
bone marrow 0
ovary 116
pancreas 20
prostate 4
stomach 36
T cells 0
Thyroid 12
uterus 127

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 5.6e−01 5.9e−01 2.5e−06 0.3 4.3e−04 0.3
bladder 5.0e−01 6.6e−01 6.3e−01 0.9 9.1e−01 0.6
bone 5.5e−01 5.8e−01 1 1.1 7.0e−01 1.3
brain 4.6e−03 6.2e−02 7.7e−11 3.0 3.2e−05 1.7
colon 8.0e−01 8.3e−01 9.8e−01 0.4 9.9e−01 0.4
epithelial 1.7e−01 9.2e−01 9.3e−07 1.3 9.7e−01 0.7
general 3.2e−04 6.1e−01 1.5e−31 2.1 1.9e−03 1.1
head and neck 1.2e−01 2.1e−01 1 1.2 1 1.1
kidney 6.9e−01 8.1e−01 1.2e−04 2.4 1.5e−02 1.5
liver 7.1e−01 7.2e−01 5.0e−04 0.2 1 0.1
lung 2.9e−01 7.1e−01 4.2e−02 1.7 5.1e−01 0.8
lymph nodes 6.3e−01 8.2e−01 9.0e−01 0.5 1 0.3
breast 4.0e−02 1.8e−01 2.1e−06 6.0 3.9e−03 3.0
bone marrow 1 6.7e−01 1 1.0 2.8e−01 2.8
ovary 6.6e−01 7.3e−01 1.3e−01 1.5 3.6e−01 1.1
pancreas 1.7e−02 9.9e−02 4.8e−10 7.6 2.9e−07 5.1
prostate 5.8e−01 6.3e−01 4.1e−02 3.9 1.8e−03 3.8
stomach 2.7e−01 7.5e−01 1.1e−01 1.5 6.5e−01 0.8
T cells 1 6.7e−01 1 1.0 7.2e−01 1.4
Thyroid 3.4e−01 3.4e−01 3.0e−01 2.2 3.0e−01 2.2
uterus 1.2e−01 5.3e−01 6.6e−02 1.4 5.4e−01 0.8

As noted above, cluster HSCOC4 features 19 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Complement C4 precursor [Contains: C4a anaphylatoxin]. A description of each variant protein according to the present invention is now provided.

Variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T1 (SEQ ID NO:387). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P3 (SEQ ID NO:488) and CO4_HUMAN (SEQ ID NO:485):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P3 (SEQ ID NO:488), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTV corresponding to amino acids 1-865 of CO4_HUMAN (SEQ ID NO:485), which also corresponds to amino acids 1-865 of HSCOC4_PEA—1_P3 (SEQ ID NO:488), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RPHRSLSIQELGEPGPSEGWGG (SEO ID NO:977) corresponding to amino acids 866-887 of HSCOC4_PEA—1_P3 (SEO ID NO:488), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P3 (SEQ ID NO:488), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RPHRSLSIQELGEPGPSEGWGG (SEQ ID NO:977) in HSCOC4_PEA—1_P3 (SEQ ID NO:488).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
869 R -> G Yes

The glycosylation sites of variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 8
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
1391 no
862 yes 862
226 yes 226
1328 no

The phosphorylation sites of variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 9 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 9
Phosphorylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
1420 no
1422 no
1417 no

Variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488) is encoded by the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T1 (SEQ ID NO:387) is shown in bold; this coding portion starts at position 501 and ends at position 3161. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P3 (SEQ ID NO:488) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3105 A -> G Yes
3167 G -> A Yes
3228 T -> C Yes
3259 G -> T Yes
3332 G -> A Yes
3490 A -> C Yes
3569 T -> C Yes
3724 G -> T Yes
3831 A -> G Yes
3898 C -> A Yes
3972 C -> T Yes
3975 G -> C Yes
3983 T -> A Yes
3986 G -> C Yes
3988 C -> T Yes
4140 G -> A Yes
4147 T -> C Yes
4228 C -> G Yes
4233 C -> T Yes
4242 G -> T Yes
4243 G -> C Yes
4339 G -> A Yes
4345 C -> G Yes
4348 G -> A Yes
4469 G -> T Yes
4562 A -> T Yes
4781 A -> G No
4873 T -> C Yes
5007 G -> No
5423 C -> G Yes
5634 G -> C No
5677 G -> A Yes
5687 A -> C Yes
5862 A -> C Yes
5868 G -> A Yes
5933 A -> C Yes

Variant protein HSCOC4_PEA—1_P5 (SEQ ID NO:489) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T3 (SEQ ID NO:389). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P5 (SEQ ID NO:489) and CO4_HUMAN (SEQ ID NO:485):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P5 (SEQ ID NO:489), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids 1-818 of CO4_HUMAN (SEQ ID NO:485), which also corresponds to amino acids 1-818 of HSCOC4_PEA—1_P5 (SEQ ID NO:489), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) corresponding to amino acids 819-843 of HSCOC4_PEA—1_P5 (SEQ ID NO:489), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1P5 (SEQ ID NO:489), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) in HSCOC4_PEA—1_P5 (SEQ ID NO:489).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P5 (SEQ ID NO:489) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P5 (SEQ ID NO:489) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
829 L -> P Yes
830 L -> I Yes
840 S -> P Yes

The glycosylation sites of variant protein HSCOC4_PEA—1_P5 (SEQ ID NO:489), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 12
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
1391 no
862 no
226 yes 226
1328 no

The phosphorylation sites of variant protein HSCOC4_PEA—1_P5 (SEQ ID NO:489), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 13 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 13
Phosphorylation site(s)
Position(s) on known
amino acid sequence Present in variant protein?
1420 no
1422 no
1417 no

Variant protein HSCOC4_PEA—1_P5 (SEQ ID NO:489) is encoded by the following transcript(s): HSCOC4_PEA—1_T3 (SEQ ID NO:389), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T3 (SEQ ID NO:389) is shown in bold; this coding portion starts at position 501 and ends at position 3029. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_l_P5 (SEQ ID NO:489) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2986 T -> C Yes
2988 C -> A Yes
3018 T -> C Yes
3070 C -> T Yes
3081 C -> A Yes
3093 A -> G Yes
3101 G -> A Yes
3106 G -> A Yes
3174 G -> A Yes
3193 A -> G Yes
3201 T -> C Yes
3233 C -> T Yes
3363 A -> G Yes
3425 G -> A Yes
3486 T -> C Yes
3517 G -> T Yes
3590 G -> A Yes
3748 A -> C Yes
3827 T -> C Yes
3982 G -> T Yes
4089 A -> G Yes
4156 C -> A Yes
4230 C -> T Yes
4233 G -> C Yes
4241 T -> A Yes
4244 G -> C Yes
4246 C -> T Yes
4398 G -> A Yes
4405 T -> C Yes
4486 C -> G Yes
4491 C -> T Yes
4500 G -> T Yes
4501 G -> C Yes
4597 G -> A Yes
4603 C -> G Yes
4606 G -> A Yes
4727 G -> T Yes
4820 A -> T Yes
5039 A -> G No
5131 T -> C Yes
5265 G -> No
5681 C -> G Yes
5892 G -> C No
5935 G -> A Yes
5945 A -> C Yes
6120 A -> C Yes
6126 G -> A Yes
6191 A -> C Yes

Variant protein HSCOC4_PEA—1_P6 (SEQ ID NO:490) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T4 (SEQ ID NO:390). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P6 (SEQ ID NO:490) and CO4_HUMAN (SEQ ID NO:485):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P6 (SEQ ID NO:490), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKG corresponding to amino acids 1-1052 of CO4_HUMAN (SEQ ID NO:485), which also corresponds to amino acids 1-1052 of HSCOC4_PEA—1_P6 (SEQ ID NO:490), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP (SEQ ID NO:979) corresponding to amino acids 1053-1084 of HSCOC4_PEA—1_P6 (SEQ ID NO:490), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P6 (SEQ ID NO:490), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP (SEQ ID NO:979) in HSCOC4_PEA—1_P6 (SEQ ID NO:490).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P6 (SEQ ID NO:490) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P6 (SEQ ID NO:490) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1062 G -> V Yes
1068 T -> Yes

The glycosylation sites of variant protein HSCOC4_PEA—1_P6 (SEQ ID NO:490), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 16 (given according to their position(s) on the amino acid sequence in the column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 16
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
1391 no
862 yes 862
226 yes 226
1328 no

The phosphorylation sites of variant protein HSCOC4_PEA—1P6 (SEQ ID NO:490), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 17 (given according to their position(s) on the amino acid sequence in the column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 17
Phosphorylation site(s)
Position(s) on known amino
acid sequence Present in variant protein?
1420 no
1422 no
1417 no

Variant protein HSCOC4_PEA—1_P6 (SEQ ID NO:490) is encoded by the following transcript(s): HSCOC4_PEA—1_T4 (SEQ ID NO:390), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T4 (SEQ ID NO:390) is shown in bold; this coding portion starts at position 501 and ends at position 3752. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P6 (SEQ ID NO:490) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3685 G -> T Yes
3702 A -> Yes
3897 A -> G Yes
3964 C -> A Yes
4038 C -> T Yes
4041 G -> C Yes
4049 T -> A Yes
4052 G -> C Yes
4054 C -> T Yes
4206 G -> A Yes
4213 T -> C Yes
4294 C -> G Yes
4299 C -> T Yes
4308 G -> T Yes
4309 G -> C Yes
4405 G -> A Yes
4411 C -> G Yes
4414 G -> A Yes
4535 G -> T Yes
4628 A -> T Yes
4847 A -> G No
4939 T -> C Yes
5073 G -> No
5489 C -> G Yes
5700 G -> C No
5743 G -> A Yes
5753 A -> C Yes
5928 A -> C Yes
5934 G -> A Yes
5999 A -> C Yes

Variant protein HSCOC4_PEA—1_P12 (SEQ ID NO:491) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T11 (SEQ ID NO:394). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P12 (SEQ ID NO:491) and CO4_HUMAN_V1 (SEQ ID NO: 486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P12 (SEQ ID NO:491), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NRSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKV corresponding to amino acids 1-1380 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1380 of HSCOC4_PEA—1_P12 (SEQ ID NO:491), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RAREGVGPGTGGGEGVE (SEQ ID NO:980) corresponding to amino acids 1381-1397 of HSCOC4_PEA—1_P12 (SEQ ID NO:491), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P12 (SEQ ID NO:491), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RAREGVGPGTGGGEGVE (SEQ ID NO:980) in HSCOC4_PEA—1_P12 (SEQ ID NO:491).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 19
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P12 (SEQ ID NO:491) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P12 (SEQ ID NO:491) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20
Amino acid mutations
SNP position(s) on amino Alternative amino
acid sequence acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes

Variant protein HSCOC4_PEA—1_P12 (SEQ ID NO:491) is encoded by the following transcript(s): HSCOC4_PEA—1_T11 (SEQ ID NO:394), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T11 (SEQ ID NO:394) is shown in bold; this coding portion starts at position 501 and ends at position 4691. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P12 (SEQ ID NO:491) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4859 C -> T Yes
4876 C -> A Yes
4882 C -> G Yes
4924 G -> A Yes
5205 C -> G Yes
5596 C -> T Yes
5717 A -> G No
5809 T -> C Yes
5943 G -> No
6359 C -> G Yes
6570 G -> C No
6613 G -> A Yes
6623 A -> C Yes
6798 A -> C Yes
6804 G -> A Yes
6869 A -> C Yes

Variant protein HSCOC4_PEA—1_P15 (SEQ ID NO:492) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T14 (SEQ ID NO:396). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P15 (SEQ ID NO:492) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P15 (SEQ ID NO:492), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQ corresponding to amino acids 1-1359 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1359 of HSCOC4_PEA—1_P15 (SEQ ID NO:492), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL (SEQ ID NO:981) corresponding to amino acids 1360-1415 of HSCOC4_PEA—1_P15 (SEQ ID NO:492, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P15 (SEQ ID NO:492), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL (SEQ ID NO:981) in HSCOC4_PEA—1_P15 (SEQ ID NO:492).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 22
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P15 (SEQ ID NO:492) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P15 (SEQ ID NO:492) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> V No
322 A -> No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1387 Q -> H Yes
1411 R -> C Yes

Variant protein HSCOC4_PEA—1_P15 (SEQ ID NO:492) is encoded by the following transcript(s): HSCOC4_PEA—1_T14 (SEQ ID NO:396), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T14 (SEQ ID NO:396) is shown in bold; this coding portion starts at position 501 and ends at position 4745. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P15 (SEQ ID NO:492) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4661 A -> C Yes
4731 C -> T Yes
4872 A -> G Yes
4905 C -> T Yes
5061 A -> G No
5153 T -> C Yes
5287 G -> No
5703 C -> G Yes
5914 G -> C No
5957 G -> A Yes
5967 A -> C Yes
6142 A -> C Yes
6148 G -> A Yes
6213 A -> C Yes

Variant protein HSCOC4_PEA—1_P16 (SEQ ID NO:493) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T15 (SEQ ID NO:397). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P16 (SEQ ID NO:493) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P16 (SEQ ID NO:493), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPK corresponding to amino acids 1-1457 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1457 of HSCOC4_PEA—1_P16 (SEQ ID NO:493), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AERQGGAVWHGHRGRHPPEWIPRPAC (SEQ ID NO:982) corresponding to amino acids 1458-1483 of HSCOC4_PEA—1_P16 (SEQ ID NO:493), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P16 (SEQ ID NO:493), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AERQGGAVWHGHRGRHPPEWIPRPAC (SEQ ID NO:982) in HSCOC4_PEA—1_P16 (SEQ ID NO:493).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 25
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure.

Variant protein HSCOC4_PEA—1_P16 (SEQ ID NO:493) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 26, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P16 (SEQ ID NO:493) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No

Variant protein HSCOC4_PEA—1_P16 (SEQ ID NO:493) is encoded by the following transcript(s): HSCOC4_PEA—1_T15 (SEQ ID NO:397), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T15 (SEQ ID NO:397) is shown in bold; this coding portion starts at position 501 and ends at position 4949. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA_l_P16 (SEQ ID NO:493) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
5263 C -> G Yes
5474 G -> C No
5517 G -> A Yes
5527 A -> C Yes
5702 A -> C Yes
5708 G -> A Yes
5773 A -> C Yes

Variant protein HSCOC4_PEA—1_P20 (SEQ ID NO:494) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T20 (SEQ ID NO:398). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P20 (SEQ ID NO:494) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P20 (SEQ ID NO:494), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQ corresponding to amino acids 1-1303 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1303 of HSCOC4_PEA—1_P20 (SEQ ID NO:494), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH (SEO ID NO:983) corresponding to amino acids 1304-1349 of HSCOC4_PEA—1_P20 (SEO ID NO:494), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P20 (SEQ ID NO:494), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO:983)
VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH
in HSCOC4_PEA_1_P20 (SEQ ID NO:494).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 28
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P20 (SEQ ID NO:494) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 29, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P20 (SEQ ID NO:494) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1312 R -> G Yes
1344 D -> V Yes

Variant protein HSCOC4_PEA—1_P20 (SEQ ID NO:494) is encoded by the following transcript(s): HSCOC4_PEA—1_T20 (SEQ ID NO:398), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T20 (SEQ ID NO:398) is shown in bold; this coding portion starts at position 501 and ends at position 4547. The transcript also has the following SNPs as listed in Table 30 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P20 (SEQ ID NO:494) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 30
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4434 C -> G Yes
4531 A -> T Yes
4743 A -> C Yes
4813 C -> T Yes
4954 A -> G Yes
4987 C -> T Yes
5143 A -> G No
5235 T -> C Yes
5369 G -> No
5785 C -> G Yes
5996 G -> C No
6039 G -> A Yes
6049 A -> C Yes
6224 A -> C Yes
6230 G -> A Yes
6295 A -> C Yes

Variant protein HSCOC4_PEA—1_P9 (SEQ ID NO:495) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T21 (SEQ ID NO:399). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to, the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P9 (SEQ ID NO:495) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P9 (SEQ ID NO:495), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1-1529 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1529 of HSCOC4_PEA—1_P9 (SEQ ID NO:495), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER (SEQ ID NO:984) corresponding to amino acids 1530-1533 of HSCOC4_PEA—1_P9 (SEQ ID NO:495), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P9 (SEQ ID NO:495), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER (SEQ ID NO:984) in HSCOC4_PEA—1_P9 (SEQ ID NO:495).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 31
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P9 (SEQ ID NO:495) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 32, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P9 (SEQ ID NO:495) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 32
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> V No
322 A -> No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No

Variant protein HSCOC4_PEA—1_P9 (SEQ ID NO:495) is encoded by the following transcript(s): HSCOC4_PEA1_T21 (SEQ ID NO:399), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T21 (SEQ ID NO:399) is shown in bold; this coding portion starts at position 501 and ends at position 5099. The transcript also has the following SNPs as listed in Table 33 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P9 (SEQ ID NO:495) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 33
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5561 G -> A Yes
6026 T -> G Yes
6348 G -> C Yes
6966 C -> G Yes
7177 G -> C No
7220 G -> A Yes
7230 A -> C Yes
7405 A -> C Yes
7411 G -> A Yes
7476 A -> C Yes

Variant protein HSCOC4_PEA—1_P22 (SEQ ID NO:496) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T25 (SEQ ID NO:400). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P22 (SEQ ID NO:496) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P22 (SEQ ID NO:496), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LASLVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAF RLFETKITQVLHF corresponding to amino acids 1-1653 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1653 of HSCOC4_PEA—1_P22 (SEQ ID NO:496), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SMKQTGEAGRAGGRQGG (SEQ ID NO:985) corresponding to amino acids 1654-1670 of HSCOC4_PEA—1_P22 (SEQ ID NO:496), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P22 (SEQ ID NO:496), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SMKQTGEAGRAGGRQGG (SEQ ID NO:985) in HSCOC4_PEA—1_P22 (SEQ ID NO:496).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 34
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P22 (SEQ ID NO:496) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 35, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P22 (SEQ ID NO:496) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 35
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No
1604 R -> G Yes

Variant protein HSCOC4_PEA—1_P22 (SEQ ID NO:496) is encoded by the following transcript(s): HSCOC4_PEA—1_T25 (SEQ ID NO:400), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T25 (SEQ ID NO:400) is shown in bold; this coding portion starts at position 501 and ends at position 5510. The transcript also has the following SNPs as listed in Table 36 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P22 (SEQ ID NO:496) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 36
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5310 C -> G Yes
5783 G -> C No
5826 G -> A Yes
5836 A -> C Yes
5974 C -> T Yes
5981 C -> T Yes
6154 A -> C Yes
6160 G -> A Yes
6225 A -> C Yes
6283 C -> T Yes
6548 C -> T Yes
6567 C -> T Yes
7300 C -> A Yes
7520 C -> T Yes
7685 A -> C Yes

Variant protein HSCOC4_PEA—1_P23 (SEQ ID NO:497) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T28 (SEQ ID NO:401). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P23 (SEQ ID NO:497) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P23 (SEQ ID NO:497), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKANEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYG corresponding to amino acids 1-1626 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1626 of HSCOC4_PEA—1_P23 (SEQ ID NO:497), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS (SEQ ID NO:986) corresponding to amino acids 1627-1685 of HSCOC4_PEA—1_P23 (SEQ ID NO:497), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P23 (SEQ ID NO:497), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO:986)
QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNS
PFPLLLTPS in HSCOC4_PEA_1_P23 (SEQ ID NO:497).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 37
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure.

Variant protein HSCOC4_PEA—1_P23 (SEQ ID NO:497) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 38, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P23 (SEQ ID NO:497) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 38
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> V No
322 A -> No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No
1604 R -> G Yes
1634 G -> Yes

Variant protein HSCOC4_PEA—1_P23 (SEQ ID NO:497) is encoded by the following transcript(s): HSCOC4_PEA—1_T28 (SEQ ID NO:401), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T28 (SEQ ID NO:401) is shown in bold; this coding portion starts at position 501 and ends at position 5555. The transcript also has the following SNPs as listed in Table 39 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P23 (SEQ ID NO:497) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 39
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5310 C -> G Yes
5402 C -> Yes
5426 T -> C Yes
5965 G -> C No
6008 G -> A Yes
6018 A -> C Yes
6156 C -> T Yes
6163 C -> T Yes
6336 A -> C Yes
6342 G -> A Yes
6407 A -> C Yes
6465 C -> T Yes
6730 C -> T Yes
6749 C -> T Yes
7482 C -> A Yes
7702 C -> T Yes
7867 A -> C Yes

Variant protein HSCOC4_PEA—1_P24 (SEQ ID NO:498) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T30 (SEQ ID NO:402). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P24 (SEQ ID NO:498) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P24 (SEQ ID NO:498), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDS corresponding to amino acids 1-1528 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1528 of HSCOC4_PEA—1_P24 (SEQ ID NO:498), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG (SEQ ID NO:987) corresponding to amino acids 1529-1579 of HSCOC4_PEA—1_P24 (SEQ ID NO:498), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P24 (SEQ ID NO:498), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO:987)
SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRT
RMATG in HSCOC4_PEA_1_P24 (SEQ ID NO:498).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 40
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P24 (SEQ ID NO:498) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 41, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P24 (SEQ ID NO:498) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 41
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No
1569 S -> R Yes

Variant protein HSCOC4_PEA—1_P24 (SEQ ID NO:498) is encoded by the following transcript(s): HSCOC4_PEA—1_T30 (SEQ ID NO:402), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T30 (SEQ ID NO:402) is shown in bold; this coding portion starts at position 501 and ends at position 5237. The transcript also has the following SNPs as listed in Table 42 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P24 (SEQ ID NO:498) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 42
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5207 C -> G Yes
5418 G -> C No
5461 G -> A Yes
5471 A -> C Yes
5646 A -> C Yes
5652 G -> A Yes
5717 A -> C Yes

Variant protein HSCOC4_PEA—1_P25 (SEQ ID NO:499) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T31 (SEQ ID NO:403). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P25 (SEQ ID NO:499) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P25 (SEQ ID NO:499), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1-1593 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1593 of HSCOC4_PEA—1_P25 (SEQ ID NO:499), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG (SEQ ID NO:988) corresponding to amino acids 1594-1657 of HSCOC4_PEA—1_P25 (SEQ ID NO:499), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P25 (SEQ ID NO:499) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO:988)
ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDE
VCLLLPPCGVRLPG in HSCOC4_PEA_1_P25 (SEQ ID NO:
499).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 43
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P25 (SEQ ID NO:499) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 44, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P25 (SEQ ID NO:499) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 44
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No
1632 A -> G Yes

Variant protein HSCOC4_PEA—1_P25 (SEQ ID NO:499) is encoded by the following transcript(s): HSCOC4_PEA—1_T31 (SEQ ID NO:403), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T31 (SEQ ID NO:403) is shown in bold; this coding portion starts at position 501 and ends at position 5471. The transcript also has the following SNPs as listed in Table 45 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P25 (SEQ ID NO:499) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 45
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5395 C -> G Yes
5606 G -> C No
5649 G -> A Yes
5659 A -> C Yes
5834 A -> C Yes
5840 G -> A Yes
5905 A -> C Yes

Variant protein HSCOC4_PEA—1_P26 (SEQ ID NO:500) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T32 (SEQ ID NO:404). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P26 (SEQ ID NO:500) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P26 (SEQ ID NO:500), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1-1593 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1593 of HSCOC4_PEA—1_P26 (SEQ ID NO:500), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

(SEQ ID NO:989)
ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDE
VCLLLPPCGVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL

corresponding to amino acids 1594-1691 of HSCOC4_PEA—1_P26 (SEQ ID NO:500), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P26 (SEQ ID NO:500), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

(SEQ ID NO:989)
ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDE
VCLLLPPCGVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL
in HSCOC4_PEA_1_P26 (SEQ ID NO:500).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 46
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P26 (SEQ ID NO:500) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 47, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P26 (SEQ ID NO:500) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 47
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No
1632 A -> G Yes
1663 P -> Yes
1671 C -> R Yes

Variant protein HSCOC4_PEA—1_P26 (SEQ ID NO:500) is encoded by the following transcript(s): HSCOC4_PEA—1_T32 (SEQ ID NO:404), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T32 (SEQ ID NO:404) is shown in bold; this coding portion starts at position 501 and ends at position 5573. The transcript also has the following SNPs as listed in Table 48 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P26 (SEQ ID NO:500) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 48
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5395 C -> G Yes
5487 C -> Yes
5511 T -> C Yes
6050 G -> C No
6093 G -> A Yes
6103 A -> C Yes
6278 A -> C Yes
6284 G -> A Yes
6349 A -> C Yes
6407 C -> T Yes
6672 C -> T Yes
6691 C -> T Yes
7424 C -> A Yes
7644 C -> T Yes
7809 A -> C Yes

Variant protein HSCOC4_PEA—1_P30 (SEQ ID NO:501) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T40 (SEQ ID NO:405). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P30 (SEQ ID NO:501) and CO4_HUMAN_V3 (SEQ ID NO: 487):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P30 (SEQ ID NO:501), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGS corresponding to amino acids 1-1232 of CO4_HUMAN_V3 (SEQ ID NO:487), which also corresponds to amino acids 1-1232 of HSCOC4_PEA—1_P30 (SEQ ID NO:501), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RNPVRLLQPRAQMFCVLRGTK (SEQ ID NO:990) corresponding to amino acids 1233-1253 of HSCOC4_PEA—1P30 (SEQ ID NO:501), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P30 (SEQ ID NO:501), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RNPVRLLQPRAQMFCVLRGTK (SEQ ID NO:990) in HSCOC4_PEA—1_P30 (SEQ ID NO:501).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN (SEQ ID NO:485)_V3 (SEQ ID NO:487). These changes were previously known to occur and are listed in the table below.

TABLE 49
Changes to CO4_HUMAN (SEQ ID NO: 485) _V3 (SEQ ID NO: 487)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P30 (SEQ ID NO:501) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 50, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P30 (SEQ ID NO:501) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 50
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes

Variant protein HSCOC4_PEA—1_P30 (SEQ ID NO:501) is encoded by the following transcript(s): HSCOC4_PEA—1_T40 (SEQ ID NO:405), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T40 (SEQ ID NO:405) is shown in bold; this coding portion starts at position 501 and ends at position 4259. The transcript also has the following SNPs as listed in Table 51 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P30 (SEQ ID NO:501) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 51
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4348 C -> G Yes
4559 G -> C No
4602 G -> A Yes
4612 A -> C Yes
4787 A -> C Yes
4793 G -> A Yes
4858 A -> C Yes

Variant protein HSCOC4_PEA—1_P38 (SEQ ID NO:502) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T2 (SEQ ID NO:388). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P38 (SEQ ID NO:502) and CO4_HUMAN (SEQ ID NO:485):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P38 (SEQ ID NO:502), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids 1-818 of CO4_HUMAN (SEQ ID NO:485), which also corresponds to amino acids 1-818 of HSCOC4_PEA—1_P38 (SEQ ID NO:502), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) corresponding to amino acids 819-843 of HSCOC4_PEA—1_P38 (SEQ ID NO:502), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P38 (SEQ ID NO:502) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) in HSCOC4_PEA—1_P38 (SEQ ID NO:502).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P38 (SEQ ID NO:502) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 52, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P38 (SEQ ID NO:502) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 52
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
829 L -> P Yes
830 L -> I Yes
840 S -> P Yes

The glycosylation sites of variant protein HSCOC4_PEA—1_P38 (SEQ ID NO:502), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 53 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 53
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
1391 no
862 no
226 yes 226
1328 no

The phosphorylation sites of variant protein HSCOC4_PEA—1_P38 (SEQ ID NO:502), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 54 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 54
Phosphorylation site(s)
Position(s) on known amino
acid sequence Present in variant protein?
1420 no
1422 no
1417 no

Variant protein HSCOC4_PEA—1_P38 (SEQ ID NO:502) is encoded by the following transcript(s): HSCOC4_PEA—1_T2 (SEQ ID NO:388), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T2 (SEQ ID NO:388) is shown in bold; this coding portion starts at position 501 and ends at position 3029. The transcript also has the following SNPs as listed in Table 55 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA1_P38 (SEQ ID NO:502) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 55
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2986 T -> C Yes
2988 C -> A Yes
3018 T -> C Yes
3070 C -> T Yes
3081 C -> A Yes
3093 A -> G Yes
3101 G -> A Yes
3106 G -> A Yes
3174 G -> A Yes
3193 A -> G Yes
3201 T -> C Yes
3233 C -> T Yes
3373 T -> C Yes
3404 G -> T Yes
3477 G -> A Yes
3635 A -> C Yes
3714 T -> C Yes
3869 G -> T Yes
3976 A -> G Yes
4043 C -> A Yes
4117 C -> T Yes
4120 G -> C Yes
4128 T -> A Yes
4131 G -> C Yes
4133 C -> T Yes
4285 G -> A Yes
4292 T -> C Yes
4373 C -> G Yes
4378 C -> T Yes
4387 G -> T Yes
4388 G -> C Yes
4484 G -> A Yes
4490 C -> G Yes
4493 G -> A Yes
4614 G -> T Yes
4707 A -> T Yes
4926 A -> G No
5018 T -> C Yes
5152 G -> No
5568 C -> G Yes
5779 G -> C No
5822 G -> A Yes
5832 A -> C Yes
6007 A -> C Yes
6013 G -> A Yes
6078 A -> C Yes

Variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T5 (SEQ ID NO:391). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P39 (SEQ ID NO:503) and CO4_HUMAN (SEQ ID NO:485):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P39 (SEQ ID NO:503), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ corresponding to amino acids 1-387 of CO4_HUMAN (SEQ ID NO:485), which also corresponds to amino acids 1-387 of HSCOC4_PEA—1_P39 (SEQ ID NO:503), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSSRGEG (SEQ ID NO:992) corresponding to amino acids 388-394 of HSCOC4_PEA—1_P39 (SEQ ID NO:503), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P39 (SEQ ID NO:503), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSSRGEG (SEQ ID NO:992) in HSCOC4_PEA—1_P39 (SEQ ID NO:503).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 56, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 56
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> No
322 A -> V No
347 S -> Y Yes

The glycosylation sites of variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 57 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 57
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
1391 no
862 no
226 yes 226
1328 no

The phosphorylation sites of variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 58 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 58
Phosphorylation site(s)
Position(s) on known amino
acid sequence Present in variant protein?
1420 no
1422 no
1417 no

Variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503) is encoded by the following transcript(s): HSCOC4_PEA—1_T5 (SEQ ID NO:391), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T5 (SEQ ID NO:391) is shown in bold; this coding portion starts at position 501 and ends at position 1682. The transcript also has the following SNPs as listed in Table 59 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P39 (SEQ ID NO:503) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 59
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1742 C -> A Yes
1756 C -> A Yes
1867 A -> No
1877 C -> T Yes
2032 C -> T Yes
2084 C -> T Yes
2245 A -> C Yes
2261 G -> A Yes
2421 C -> G Yes
2448 A -> G Yes
2534 G -> A Yes
2639 C -> T No
2776 C -> T Yes
3074 C -> T Yes
3214 T -> C Yes
3245 G -> T Yes
3318 G -> A Yes
3476 A -> C Yes
3555 T -> C Yes
3710 G -> T Yes
3817 A -> G Yes
3884 C -> A Yes
3958 C -> T Yes
3961 G -> C Yes
3969 T -> A Yes
3972 G -> C Yes
3974 C -> T Yes
4126 G -> A Yes
4133 T -> C Yes
4214 C -> G Yes
4219 C -> T Yes
4228 G -> T Yes
4229 G -> C Yes
4325 G -> A Yes
4331 C -> G Yes
4334 G -> A Yes
4455 G -> T Yes
4548 A -> T Yes
4767 A -> G No
4859 T -> C Yes
4993 G -> No
5409 C -> G Yes
5620 G -> C No
5663 G -> A Yes
5673 A -> C Yes
5848 A -> C Yes
5854 G -> A Yes
5919 A -> C Yes

Variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T7 (SEQ ID NO:392). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P40 (SEQ ID NO:504) and CO4_HUMAN (SEQ ID NO:485):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P40 (SEQ ID NO:504), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY corresponding to amino acids 1-236 of CO4_HUMAN (SEQ ID NO:485), which also corresponds to amino acids 1-236 of HSCOC4_PEA—1_P40 (SEQ ID NO:504), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY (SEQ ID NO:993) corresponding to amino acids 237-263 of HSCOC4_PEA—1_P40 (SEQ ID NO:504), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P40 (SEQ ID NO:504), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY (SEQ ID NO:993) in HSCOC4_PEA—1_P40 (SEQ ID NO:504).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 60, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 60
Amino acid mutations
SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
254 R -> No

The glycosylation sites of variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 61 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 61
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
1391 no
862 no
226 yes 226
1328 no

The phosphorylation sites of variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504), as compared to the known protein Complement C4 precursor [Contains: C4a anaphylatoxin], are described in Table 62 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 62
Phosphorylation site(s)
Position(s) on known amino
acid sequence Present in variant protein?
1420 no
1422 no
1417 no

Variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504) is encoded by the following transcript(s): HSCOC4_PEA—1_T7 (SEQ ID NO:392), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T7 (SEQ ID NO:392) is shown in bold; this coding portion starts at position 501 and ends at position 1289. The transcript also has the following SNPs as listed in Table 63 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P40 (SEQ ID NO:504) sequence provides support for the deduced sequence variant protein according to the present invention).

TABLE 63
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1262 C -> No
1262 C -> T No
1314 C -> T Yes
1337 C -> A Yes
1565 A -> No
1575 C -> T Yes
1730 C -> T Yes
1782 C -> T Yes
1943 A -> C Yes
1959 G -> A Yes
2119 C -> G Yes
2146 A -> G Yes
2232 G -> A Yes
2337 C -> T No
2474 C -> T Yes
2772 C -> T Yes
2912 T -> C Yes
2943 G -> T Yes
3016 G -> A Yes
3174 A -> C Yes
3253 T -> C Yes
3408 G -> T Yes
3515 A -> G Yes
3582 C -> A Yes
3656 C -> T Yes
3659 G -> C Yes
3667 T -> A Yes
3670 G -> C Yes
3672 C -> T Yes
3824 G -> A Yes
3831 T -> C Yes
3912 C -> G Yes
3917 C -> T Yes
3926 G -> T Yes
3927 G -> C Yes
4023 G -> A Yes
4029 C -> G Yes
4032 G -> A Yes
4153 G -> T Yes
4246 A -> T Yes
4465 A -> G No
4557 T -> C Yes
4691 G -> No
5107 C -> G Yes
5318 G -> C No
5361 G -> A Yes
5371 A -> C Yes
5546 A -> C Yes
5552 G -> A Yes
5617 A -> C Yes

Variant protein HSCOC4_PEA—1_P41 (SEQ ID NO:505) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T8 (SEQ ID NO:393). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P41 (SEQ ID NO:505) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P41 (SEQ ID NO:505), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1-1529 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1529 of HSCOC4_PEA—1_P41 (SEQ ID NO:505), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER (SEQ ID NO:984) corresponding to amino acids 1530-1533 of HSCOC4_PEA—1_P41 (SEQ ID NO:505), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P41 (SEQ ID NO:505), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER (SEQ ID NO:984) in HSCOC4_PEA—1_P41 (SEQ ID NO:505).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 64
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure.

Variant protein HSCOC4_PEA—1_P41 (SEQ ID NO:505) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 65, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P41 (SEQ ID NO:505) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 65
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> V No
322 A -> No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No

Variant protein HSCOC4_PEA—1_P41 (SEQ ID NO:505) is encoded by the following transcript(s): HSCOC4_PEA—1_T8 (SEQ ID NO:393), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T8 (SEQ ID NO:393) is shown in bold; this coding portion starts at position 501 and ends at position 5099. The transcript also has the following SNPs as listed in Table 66 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P41 (SEQ ID NO:505) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 66
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5561 G -> A Yes
6026 T -> G Yes
6348 G -> C Yes
6801 C -> G Yes
7012 G -> C No
7055 G -> A Yes
7065 A -> C Yes
7240 A -> C Yes
7246 G -> A Yes
7311 A -> C Yes

Variant protein HSCOC4_PEA—1_P42 (SEQ ID NO:506) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSCOC4_PEA—1_T12 (SEQ ID NO:395). An alignment is given to the known protein (Complement C4 precursor [Contains: C4a anaphylatoxin]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSCOC4_PEA—1_P42 (SEQ ID NO:506) and CO4_HUMAN_V1 (SEQ ID NO:486):

1. An isolated chimeric polypeptide encoding for HSCOC4_PEA—1_P42 (SEQ ID NO:506), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIW corresponding to amino acids 1-1473 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1473 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR (SEQ ID NO:1021) corresponding to amino acids 1474-1511 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), a third amino acid sequence being at least 90% homologous to RNGKVGLSGMAIADVTLLSGFHALRADLEK corresponding to amino acids 1474-1503 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1512-1541 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWSATQGNPLCPRY (SEQ ID NO:995) corresponding to amino acids 1542-1555 of HSCOC4_PEA—1_P42 (SEQ ID NO:506), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of HSCOC4_PEA—1_P42 (SEQ ID NO:506), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR (SEQ ID NO: 1021), corresponding to HSCOC4_PEA—1_P42 (SEQ ID NO:506).

3. An isolated polypeptide encoding for a tail of HSCOC4_PEA—1_P42 (SEQ ID NO:506), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWSATQGNPLCPRY (SEQ ID NO:995) in HSCOC4_PEA—1_P42 (SEQ ID NO:506).

It should be noted that the known protein sequence (CO4_HUMAN (SEQ ID NO:485) ) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CO4_HUMAN_V1 (SEQ ID NO:486). These changes were previously known to occur and are listed in the table below.

TABLE 67
Changes to CO4_HUMAN_V1 (SEQ ID NO: 486)
SNP position(s) on
amino acid sequence Type of change
1177 variant
1202 variant
1208 variant
1211 variant
1287 variant

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSCOC4_PEA—1_P42 (SEQ ID NO:506) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 68, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P42 (SEQ ID NO:506) sequence provides support for the deduced sequence s variant protein according to the present invention).

TABLE 68
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
128 Q -> No
141 L -> V Yes
183 G -> No
211 G -> No
322 A -> V No
322 A -> No
347 S -> Y Yes
423 Q -> No
478 P -> L Yes
549 H -> P Yes
608 L -> V Yes
617 K -> E Yes
726 P -> L Yes
872 V -> A Yes
907 A -> T Yes
959 E -> D Yes
1073 D -> G Yes
1120 P -> L Yes
1121 C -> S Yes
1124 L -> I Yes
1125 D -> H Yes
1176 S -> N Yes
1207 A -> V Yes
1210 R -> L Yes
1286 A -> S Yes
1317 I -> F Yes
1390 K -> E No
1465 R -> No

Variant protein HSCOC4_PEA—1_P42 (SEQ ID NO:506) is encoded by the following transcript(s): HSCOC4_PEA—1_T12 (SEQ ID NO:395), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSCOC4_PEA—1_T12 (SEQ ID NO:395) is shown in bold; this coding portion starts at position 501 and ends at position 5165. The transcript also has the following SNPs as listed in Table 69 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSCOC4_PEA—1_P42 (SEQ ID NO:506) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 69
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
304 A -> G Yes
884 G -> No
921 C -> G Yes
1049 C -> No
1131 G -> No
1465 C -> No
1465 C -> T No
1517 C -> T Yes
1540 C -> A Yes
1768 A -> No
1778 C -> T Yes
1933 C -> T Yes
1985 C -> T Yes
2146 A -> C Yes
2162 G -> A Yes
2322 C -> G Yes
2349 A -> G Yes
2435 G -> A Yes
2540 C -> T No
2677 C -> T Yes
2975 C -> T Yes
3115 T -> C Yes
3146 G -> T Yes
3219 G -> A Yes
3377 A -> C Yes
3456 T -> C Yes
3611 G -> T Yes
3718 A -> G Yes
3785 C -> A Yes
3859 C -> T Yes
3862 G -> C Yes
3870 T -> A Yes
3873 G -> C Yes
3875 C -> T Yes
4027 G -> A Yes
4034 T -> C Yes
4115 C -> G Yes
4120 C -> T Yes
4129 G -> T Yes
4130 G -> C Yes
4226 G -> A Yes
4232 C -> G Yes
4235 G -> A Yes
4356 G -> T Yes
4449 A -> T Yes
4668 A -> G No
4760 T -> C Yes
4894 G -> No
5765 G -> A Yes
6230 T -> G Yes
6552 G -> C Yes
7005 C -> G Yes
7216 G -> C No
7259 G -> A Yes
7269 A -> C Yes
7444 A -> C Yes
7450 G -> A Yes
7515 A -> C Yes

As noted above, cluster HSCOC4 features 79 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSCOC4_PEA—1_node—1 (SEQ ID NO:406) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1 535
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1 535
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1 535
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1 535
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1 535
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1 535
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1 535
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1 535
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1 535
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1 535
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1 535
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1 535
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1 535
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1 535
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1 535
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1 535
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1 535
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1 535
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1 535
NO: 405)

Segment cluster HSCOC4_PEA—1_node—5 (SEQ ID NO:407) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 566 764
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 566 764
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 566 764
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 566 764
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 566 764
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 566 764
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 566 764
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 566 764
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 566 764
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 566 764
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 566 764
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 566 764
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 566 764
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 566 764
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 566 764
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 566 764
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 566 764
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 566 764
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 566 764
NO: 405)

Segment cluster HSCOC4_PEA—1_node—7 (SEQ ID NO:408) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 765 885
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 765 885
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 765 885
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 765 885
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 765 885
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 765 885
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 765 885
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 765 885
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 765 885
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 765 885
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 765 885
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 765 885
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 765 885
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 765 885
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 765 885
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 765 885
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 765 885
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 765 885
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 765 885
NO: 405)

Segment cluster HSCOC4_PEA—1_node—30 (SEQ ID NO:409) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11(SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 73 below describes the starting and ending position of this segment on each transcript.

TABLE 73
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1662 1841
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1662 1841
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1662 1841
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1662 1841
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1761 1940
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1459 1638
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1662 1841
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1662 1841
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1662 1841
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1662 1841
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1662 1841
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1662 1841
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1662 1841
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1662 1841
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1662 1841
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1662 1841
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1662 1841
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1662 1841
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1662 1841
NO: 405)

Segment cluster HSCOC4_PEA—1_node—33 (SEQ ID NO:410) according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 74 below describes the starting and ending position of this segment on each transcript.

TABLE 74
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1842 2024
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1842 2024
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1842 2024
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1842 2024
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1941 2123
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1639 1821
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1842 2024
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1842 2024
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1842 2024
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1842 2024
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1842 2024
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1842 2024
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1842 2024
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1842 2024
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1842 2024
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1842 2024
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1842 2024
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1842 2024
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1842 2024
NO: 405)

Segment cluster HSCOC4_PEA—1_node—35 (SEQ ID NO:411) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 75 below describes the starting and ending position of this segment on each transcript.

TABLE 75
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2025 2210
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2025 2210
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2025 2210
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2025 2210
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2124 2309
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1822 2007
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2025 2210
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2025 2210
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2025 2210
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2025 2210
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2025 2210
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2025 2210
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2025 2210
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2025 2210
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2025 2210
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2025 2210
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2025 2210
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2025 2210
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2025 2210
NO: 405)

Segment cluster HSCOC4_PEA—1_node—37 (SEQ ID NO:412) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 76 below describes the starting and ending position of this segment on each transcript.

TABLE 76
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2211 2369
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2211 2369
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2211 2369
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2211 2369
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2310 2468
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2008 2166
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2211 2369
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2211 2369
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2211 2369
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2211 2369
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2211 2369
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2211 2369
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2211 2369
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2211 2369
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2211 2369
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2211 2369
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2211 2369
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2211 2369
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2211 2369
NO: 405)

Segment cluster HSCOC4_PEA—1_node—39 (SEQ ID NO:413) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 77 below describes the starting and ending position of this segment on each transcript.

TABLE 77
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2370 2496
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2370 2496
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2370 2496
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2370 2496
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2469 2595
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2167 2293
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2370 2496
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2370 2496
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2370 2496
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2370 2496
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2370 2496
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2370 2496
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2370 2496
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2370 2496
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2370 2496
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2370 2496
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2370 2496
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2370 2496
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2370 2496
NO: 405)

Segment cluster HSCOC4_PEA—1_node—43 (SEQ ID NO:414) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1—T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1−T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 78 below describes the starting and ending position of this segment on each transcript.

TABLE 78
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2572 2769
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2572 2769
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2572 2769
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2572 2769
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2671 2868
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2369 2566
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2572 2769
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2572 2769
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2572 2769
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2572 2769
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2572 2769
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2572 2769
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2572 2769
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2572 2769
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2572 2769
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2572 2769
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2572 2769
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2572 2769
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2572 2769
NO: 405)

Segment cluster HSCOC4_PEA—1_node—48 (SEQ ID NO:415) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T2 (SEQ ID NO:388) and HSCOC4_PEA—1_T3 (SEQ ID NO:389). Table 79 below describes the starting and ending position of this segment on each transcript.

TABLE 79
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T2 (SEQ ID 2953 3210
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2953 3210
NO: 389)

Segment cluster HSCOC4_PEA—1_node—49 (SEQ ID NO:416) according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 80 below describes the starting and ending position of this segment on each transcript.

TABLE 80
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2953 3092
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3211 3350
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 3211 3350
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2953 3092
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3052 3191
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2750 2889
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2953 3092
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2953 3092
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2953 3092
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2953 3092
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2953 3092
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2953 3092
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2953 3092
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2953 3092
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2953 3092
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2953 3092
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2953 3092
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2953 3092
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2953 3092
NO: 405)

Segment cluster HSCOC4_PEA—1_node—51 (SEQ ID NO:417) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 81 below describes the starting and ending position of this segment on each transcript.

TABLE 81
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3206 3415
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3351 3560
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 3464 3673
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3093 3302
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3192 3401
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2890 3099
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3093 3302
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3093 3302
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3093 3302
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3093 3302
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3093 3302
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3093 3302
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3093 3302
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3093 3302
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3093 3302
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3093 3302
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3093 3302
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3093 3302
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3093 3302
NO: 405)

Segment cluster HSCOC4_PEA—1_node—58 (SEQ ID NO:418) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ;ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 82 below describes the starting and ending position of this segment on each transcript.

TABLE 82
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3605 3767
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3750 3912
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 3863 4025
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3492 3654
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3591 3753
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3289 3451
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3492 3654
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3492 3654
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3492 3654
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3492 3654
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3492 3654
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3492 3654
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3492 3654
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3492 3654
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3492 3654
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3492 3654
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3492 3654
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3492 3654
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3492 3654
NO: 405)

Segment cluster HSCOC4_PEA—1_node—59 (SEQ ID NO:419) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T4 (SEQ ID NO:390). Table 83 below describes the starting and ending position of this segment on each transcript.

TABLE 83
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T4 (SEQ ID 3655 3833
NO: 390)

Segment cluster HSCOC4_PEA—1_node—62 (SEQ ID NO:420) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1—T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 84 below describes the starting and ending position of this segment on each transcript.

TABLE 84
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3844 4000
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3989 4145
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4102 4258
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3910 4066
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3830 3986
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3528 3684
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3731 3887
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3731 3887
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3731 3887
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3731 3887
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3731 3887
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3731 3887
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3731 3887
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3731 3887
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3731 3887
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3731 3887
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3731 3887
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3731 3887
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3731 3887
NO: 405)

Segment cluster HSCOC4_PEA—1_node—66 (SEQ ID NO:421) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 85 below describes the starting and ending position of this segment on each transcript.

TABLE 85
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4118 4289
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4263 4434
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4376 4547
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4184 4355
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4104 4275
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3802 3973
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4005 4176
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4005 4176
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4005 4176
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4005 4176
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4005 4176
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4005 4176
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4005 4176
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4005 4176
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4005 4176
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4005 4176
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4005 4176
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4005 4176
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4005 4176
NO: 405)

Segment cluster HSCOC4_PEA—1_node—72 (SEQ ID NO:422) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 86 below describes the starting and ending position of this segment on each transcript.

TABLE 86
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4392 4522
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4537 4667
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4650 4780
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4458 4588
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4378 4508
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4076 4206
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4279 4409
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4279 4409
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4279 4409
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4279 4409
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4279 4409
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4279 4409
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4279 4409
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4279 4409
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4279 4409
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4279 4409
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4279 4409
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4279 4409
NO: 404)

Segment cluster HSCOC4_PEA—1_node—77 (SEQ ID NO:423) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T14 (SEQ ID NO:396) and HSCOC4_PEA—1_T20 (SEQ ID NO:398). Table 87 below describes the starting and ending position of this segment on each transcript.

TABLE 87
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T14 (SEQ ID 4578 4970
NO: 396)
HSCOC4_PEA_1_T20 (SEQ ID 4660 5052
NO: 398)

Segment cluster HSCOC4_PEA—1_node—79 (SEQ ID NO:424) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T11 (SEQ ID NO:394). Table 88 below describes the starting and ending position of this segment on each transcript.

TABLE 88
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T11 (SEQ ID 4638 5686
NO: 394)

Segment cluster HSCOC4_PEA—1_node—93 (SEQ ID NO:425) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T12 (SEQ ID NO:395) and HSCOC4_PEA—1_T21 (SEQ ID NO:399). Table 89 below describes the starting and ending position of this segment on each transcript.

TABLE 89
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T8 (SEQ ID 5085 6566
NO: 393)
HSCOC4_PEA_1_T12 (SEQ ID 5289 6770
NO: 395)
HSCOC4_PEA_1_T21 (SEQ ID 5085 6566
NO: 399)

Segment cluster HSCOC4_PEA—1_node—100 (SEQ ID NO:426) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T21 (SEQ ID NO:399). Table 90 below describes the starting and ending position of this segment on each transcript.

TABLE 90
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T21 (SEQ ID 6679 6843
NO: 399)

Segment cluster HSCOC4_PEA—1_node—105 (SEQ ID NO:427) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T28 (SEQ ID NO:401) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 91 below describes the starting and ending position of this segment on each transcript.

TABLE 91
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T28 (SEQ ID 5377 5558
NO: 401)
HSCOC4_PEA_1_T32 (SEQ ID 5462 5643
NO: 404)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (with regard to breast cancer), shown in Table 92.

TABLE 92
Oligonucleotides related to this segment
Chip
Oligonucleotide name Overexpressed in cancers reference
HSCOC4_0_0_9883 (SEQ ID breast malignant tumors BRS
NO: 909)

Segment cluster HSCOC4_PEA—1_node—107 (SEQ ID NO:428) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 93 below describes the starting and ending position of this segment on each transcript.

TABLE 93
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T25 (SEQ ID 5461 5722
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5643 5904
NO: 401)
HSCOC4_PEA_1_T32 (SEQ ID 5728 5989
NO: 404)

Segment cluster HSCOC4_PEA—1_node—108 (SEQ ID NO:429) according to the present invention is supported by 120 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 94 below describes the starting and ending position of this segment on each transcript.

TABLE 94
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5574 5706
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5719 5851
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5832 5964
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5640 5772
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5560 5692
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5258 5390
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6952 7084
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6510 6642
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 7156 7288
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5854 5986
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5414 5546
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5936 6068
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 7117 7249
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5723 5855
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5905 6037
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5358 5490
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5546 5678
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5990 6122
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4499 4631
NO: 405)

Segment cluster HSCOC4_PEA—1_node—109 (SEQ ID NO:430) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T25 (SEQ ID NO:400) and HSCOC4_PEA—1_T28 (SEQ ID NO:401). Table 95 below describes the starting and ending position of this segment on each transcript.

TABLE 95
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T25 (SEQ ID 5856 5998
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 6038 6180
NO: 401)

Segment cluster HSCOC4_PEA—1_node—110 (SEQ ID NO:431) according to the present invention is supported by 97 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 96 below describes the starting and ending position of this segment on each transcript.

TABLE 96
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5707 5856
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5852 6001
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5965 6114
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5773 5922
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5693 5842
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5391 5540
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 7085 7234
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6643 6792
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 7289 7438
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5987 6136
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5547 5696
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 6069 6218
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 7250 7399
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5999 6148
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 6181 6330
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5491 5640
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5679 5828
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 6123 6272
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4632 4781
NO: 405)

Segment cluster HSCOC4_PEA—1_node—112 (SEQ ID NO:432) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 97 below describes the starting and ending position of this segment on each transcript.

TABLE 97
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5948 5989
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 6093 6134
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 6206 6247
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 6014 6055
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5934 5975
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5632 5673
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 7326 7367
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6884 6925
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 7530 7571
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 6228 6269
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5788 5829
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 6310 6351
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 7491 7532
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 6240 6619
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 6422 6801
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5732 5773
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5920 5961
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 6364 6743
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4873 4914
NO: 405)

Segment cluster HSCOC4_PEA—1_node—113 (SEQ ID NO:433) according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 98 below describes the starting and ending position of this segment on each transcript.

TABLE 98
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T25 (SEQ ID 6620 7765
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 6802 7947
NO: 401)
HSCOC4_PEA_1_T32 (SEQ ID 6744 7889
NO: 404)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HSCOC4_PEA—1_node—2 (SEQ ID NO:434) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 99 below describes the starting and ending position of this segment on each transcript.

TABLE 99
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 536 565
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 536 565
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 536 565
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 536 565
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 536 565
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 536 565
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 536 565
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 536 565
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 536 565
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 536 565
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 536 565
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 536 565
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 536 565
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 536 565
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 536 565
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 536 565
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 536 565
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 536 565
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 536 565
NO: 405)

Segment cluster HSCOC4_PEA—1_node—8 (SEQ ID NO:435) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 100 below describes the starting and ending position of this segment on each transcript.

TABLE 100
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 886 966
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 886 966
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 886 966
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 886 966
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 886 966
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 886 966
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 886 966
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 886 966
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 886 966
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 886 966
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 886 966
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 886 966
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 886 966
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 886 966
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 886 966
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 886 966
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 886 966
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 886 966
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 886 966
NO: 405)

Segment cluster HSCOC4_PEA—1_node—10 (SEQ ID NO:436) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 101 below describes the starting and ending position of this segment on each transcript.

TABLE 101
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 967 1037
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 967 1037
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 967 1037
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 967 1037
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 967 1037
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 967 1037
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 967 1037
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 967 1037
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 967 1037
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 967 1037
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 967 1037
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 967 1037
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 967 1037
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 967 1037
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 967 1037
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 967 1037
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 967 1037
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 967 1037
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 967 1037
NO: 405)

Segment cluster HSCOC4_PEA—1_node—12 (SEQ ID NO:437) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 102 below describes the starting and ending position of this segment on each transcript.

TABLE 102
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1038 1126
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1038 1126
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1038 1126
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1038 1126
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1038 1126
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1038 1126
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1038 1126
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1038 1126
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1038 1126
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1038 1126
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1038 1126
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1038 1126
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1038 1126
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1038 1126
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1038 1126
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1038 1126
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1038 1126
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1038 1126
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1038 1126
NO: 405)

Segment cluster HSCOC4_PEA—1_node—14 (SEQ ID NO:438) according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 103 below describes the starting and ending position of this segment on each transcript.

TABLE 103
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1127 1209
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1127 1209
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1127 1209
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1127 1209
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1127 1209
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1127 1209
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1127 1209
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1127 1209
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1127 1209
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1127 1209
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1127 1209
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1127 1209
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1127 1209
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1127 1209
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1127 1209
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1127 1209
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1127 1209
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1127 1209
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1127 1209
NO: 405)

Segment cluster HSCOC4_PEA—1_node—17 (SEQ ID NO:439) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 104 below describes the starting and ending position of this segment on each transcript.

TABLE 104
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1210 1306
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1210 1306
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1210 1306
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1210 1306
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1210 1306
NO: 391)
HSCOC4_PEA_1_T8 (SEQ ID 1210 1306
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1210 1306
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1210 1306
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1210 1306
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1210 1306
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1210 1306
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1210 1306
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1210 1306
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1210 1306
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1210 1306
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1210 1306
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1210 1306
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1210 1306
NO: 405)

Segment cluster HSCOC4_PEA—1_node—19 (SEQ ID NO:440) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1—T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 105 below describes the starting and ending position of this segment on each transcript.

TABLE 105
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1307 1412
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1307 1412
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1307 1412
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1307 1412
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1307 1412
NO: 391)
HSCOC4_PEA_1_T8 (SEQ ID 1307 1412
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1307 1412
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1307 1412
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1307 1412
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1307 1412
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1307 1412
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1307 1412
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1307 1412
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1307 1412
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1307 1412
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1307 1412
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1307 1412
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1307 1412
NO: 405)

Segment cluster HSCOC4_PEA—1_node—21 (SEQ ID NO:441) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 106 below describes the starting and ending position of this segment on each transcript.

TABLE 106
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1413 1439
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1413 1439
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1413 1439
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1413 1439
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1413 1439
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1210 1236
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1413 1439
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1413 1439
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1413 1439
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1413 1439
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1413 1439
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1413 1439
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1413 1439
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1413 1439
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1413 1439
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1413 1439
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1413 1439
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1413 1439
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1413 1439
NO: 405)

Segment cluster HSCOC4_PEA—1_node—22 (SEQ ID NO:442) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 107 below describes the starting and ending position of this segment on each transcript.

TABLE 107
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1440 1545
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1440 1545
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1440 1545
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1440 1545
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1440 1545
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1237 1342
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1440 1545
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1440 1545
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1440 1545
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1440 1545
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1440 1545
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1440 1545
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1440 1545
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1440 1545
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1440 1545
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1440 1545
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1440 1545
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1440 1545
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1440 1545
NO: 405)

Segment cluster HSCOC4_PEA—1_node—28 (SEQ ID NO:443) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 108 below describes the starting and ending position of this segment on each transcript.

TABLE 108
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 1546 1661
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 1546 1661
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 1546 1661
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 1546 1661
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 1546 1661
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 1343 1458
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 1546 1661
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 1546 1661
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 1546 1661
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 1546 1661
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 1546 1661
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 1546 1661
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 1546 1661
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 1546 1661
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 1546 1661
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 1546 1661
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 1546 1661
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 1546 1661
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 1546 1661
NO: 405)

Segment cluster HSCOC4_PEA—1_node—29 (SEQ ID NO:444) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T5 (SEQ ID NO:391). Table 109 below describes the starting and ending position of this segment on each transcript.

TABLE 109
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T5 (SEQ ID 1662 1760
NO: 391)

Segment cluster HSCOC4_PEA—1_node—41 (SEQ ID NO:445) according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 110 below describes the starting and ending position of this segment on each transcript.

TABLE 110
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2497 2571
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2497 2571
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2497 2571
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2497 2571
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2596 2670
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2294 2368
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2497 2571
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2497 2571
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2497 2571
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2497 2571
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2497 2571
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2497 2571
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2497 2571
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2497 2571
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2497 2571
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2497 2571
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2497 2571
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2497 2571
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2497 2571
NO: 405)

Segment cluster HSCOC4_PEA—1_node—45 (SEQ ID NO:446) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 111 below describes the starting and ending position of this segment on each transcript.

TABLE 111
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2770 2881
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2770 2881
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2770 2881
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2770 2881
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2869 2980
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2567 2678
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2770 2881
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2770 2881
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2770 2881
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2770 2881
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2770 2881
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2770 2881
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2770 2881
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2770 2881
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2770 2881
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2770 2881
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2770 2881
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2770 2881
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2770 2881
NO: 405)

Segment cluster HSCOC4_PEA—1_node—47 (SEQ ID NO:447) according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 112 below describes the starting and ending position of this segment on each transcript.

TABLE 112
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 2882 2952
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 2882 2952
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 2882 2952
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 2882 2952
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 2981 3051
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 2679 2749
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 2882 2952
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 2882 2952
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 2882 2952
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 2882 2952
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 2882 2952
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 2882 2952
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 2882 2952
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 2882 2952
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 2882 2952
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 2882 2952
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 2882 2952
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 2882 2952
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 2882 2952
NO: 405)

Segment cluster HSCOC4_PEA—1_node—50 (SEQ ID NO:448) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387) and HSCOC4_PEA—1_T3 (SEQ ID NO:389). Table 113 below describes the starting and ending position of this segment on each transcript.

TABLE 113
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3093 3205
NO: 387)
HSCOC4_PEA_1_T3 (SEQ ID 3351 3463
NO: 389)

Segment cluster HSCOC4_PEA—1_node—53 (SEQ ID NO:449) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 114 below describes the starting and ending position of this segment on each transcript.

TABLE 114
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3416 3467
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3561 3612
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 3674 3725
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3303 3354
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3402 3453
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3100 3151
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3303 3354
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3303 3354
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3303 3354
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3303 3354
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3303 3354
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3303 3354
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3303 3354
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3303 3354
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3303 3354
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3303 3354
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3303 3354
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3303 3354
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3303 3354
NO: 405)

Segment cluster HSCOC4_PEA—1_node—55 (SEQ ID NO:450) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 115 below describes the starting and ending position of this segment on each transcript.

TABLE 115
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3468 3557
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3613 3702
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 3726 3815
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3355 3444
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3454 3543
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3152 3241
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3355 3444
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3355 3444
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3355 3444
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3355 3444
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3355 3444
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3355 3444
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3355 3444
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3355 3444
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3355 3444
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3355 3444
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3355 3444
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3355 3444
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3355 3444
NO: 405)

Segment cluster HSCOC4_PEA—1_node—57 (SEQ ID NO:451) according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 116 below describes the starting and ending position of this segment on each transcript.

TABLE 116
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3558 3604
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3703 3749
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 3816 3862
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3445 3491
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3544 3590
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3242 3288
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3445 3491
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3445 3491
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3445 3491
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3445 3491
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3445 3491
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3445 3491
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3445 3491
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3445 3491
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3445 3491
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3445 3491
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3445 3491
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3445 3491
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3445 3491
NO: 405)

Segment cluster HSCOC4_PEA—1—node—60 (SEQ ID NO:452) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 117 below describes the starting and ending position of this segment on each transcript.

TABLE 117
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 3768 3843
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 3913 3988
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4026 4101
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 3834 3909
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3754 3829
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3452 3527
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3655 3730
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3655 3730
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3655 3730
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3655 3730
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3655 3730
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3655 3730
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3655 3730
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3655 3730
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3655 3730
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3655 3730
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3655 3730
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3655 3730
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3655 3730
NO: 405)

Segment cluster HSCOC4_PEA—1_node—64 (SEQ ID NO:453) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15(SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 118 below describes the starting and ending position of this segment on each transcript.

TABLE 118
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4001 4117
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4146 4262
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4259 4375
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4067 4183
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 3987 4103
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3685 3801
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 3888 4004
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 3888 4004
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 3888 4004
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 3888 4004
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 3888 4004
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 3888 4004
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 3888 4004
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 3888 4004
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 3888 4004
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 3888 4004
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 3888 4004
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 3888 4004
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 3888 4004
NO: 405)

Segment cluster HSCOC4_PEA—1_node—69 (SEQ ID NO:454) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 119 below describes the starting and ending position of this segment on each transcript.

TABLE 119
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4290 4309
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4435 4454
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4548 4567
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4356 4375
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4276 4295
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3974 3993
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4177 4196
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4177 4196
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4177 4196
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4177 4196
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4177 4196
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4177 4196
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4177 4196
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4177 4196
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4177 4196
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4177 4196
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4177 4196
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4177 4196
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4177 4196
NO: 405)

Segment cluster HSCOC4_PEA—1_node—70 (SEQ ID NO:455) according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 120 below describes the starting and ending position of this segment on each transcript.

TABLE 120
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4310 4349
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4455 4494
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4568 4607
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4376 4415
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4296 4335
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 3994 4033
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4197 4236
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4197 4236
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4197 4236
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4197 4236
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4197 4236
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4197 4236
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4197 4236
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4197 4236
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4197 4236
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4197 4236
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4197 4236
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4197 4236
NO: 404)

Segment cluster HSCOC4_PEA—1_node—71 (SEQ ID NO:456) according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1—T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 121 below describes the starting and ending position of this segment on each transcript.

TABLE 121
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4350 4391
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4495 4536
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4608 4649
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4416 4457
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4336 4377
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4034 4075
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4237 4278
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4237 4278
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4237 4278
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4237 4278
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4237 4278
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4237 4278
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4237 4278
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4237 4278
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4237 4278
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4237 4278
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4237 4278
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4237 4278
NO: 404)

Segment cluster HSCOC4_PEA—1_node—73 (SEQ ID NO:457) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T20 (SEQ ID NO:398). Table 122 below describes the starting and ending position of this segment on each transcript.

TABLE 122
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T20 (SEQ ID 4410 4491
NO: 398)

Segment cluster HSCOC4_PEA—1_node—74 (SEQ ID NO:458) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 123 below describes the starting and ending position of this segment on each transcript.

TABLE 123
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4523 4546
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4668 4691
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4781 4804
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4589 4612
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4509 4532
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4207 4230
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4410 4433
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4410 4433
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4410 4433
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4410 4433
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4410 4433
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4492 4515
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4410 4433
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4410 4433
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4410 4433
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4410 4433
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4410 4433
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4410 4433
NO: 404)

Segment cluster HSCOC4_PEA—1_node—75 (SEQ ID NO:459) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 124 below describes the starting and ending position of this segment on each transcript.

TABLE 124
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4547 4626
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4692 4771
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4805 4884
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4613 4692
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4533 4612
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4231 4310
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4434 4513
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4434 4513
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4434 4513
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4434 4513
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4434 4513
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4516 4595
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4434 4513
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4434 4513
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4434 4513
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4434 4513
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4434 4513
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4434 4513
NO: 404)

Segment cluster HSCOC4_PEA—1_node—76 (SEQ ID NO:460) according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 125 below describes the starting and ending position of this segment on each transcript.

TABLE 125
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4627 4690
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4772 4835
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4885 4948
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4693 4756
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4613 4676
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4311 4374
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4514 4577
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4514 4577
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4514 4577
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4514 4577
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4514 4577
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 4596 4659
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4514 4577
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4514 4577
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4514 4577
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4514 4577
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4514 4577
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4514 4577
NO: 404)

Segment cluster HSCOC4_PEA—1_node—78 (SEQ ID NO:461) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 126 below describes the starting and ending position of this segment on each transcript.

TABLE 126
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4691 4750
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4836 4895
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 4949 5008
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4757 4816
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4677 4736
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4375 4434
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4578 4637
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 4578 4637
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4578 4637
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 4971 5030
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4578 4637
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5053 5112
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4578 4637
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4578 4637
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4578 4637
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4578 4637
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4578 4637
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4578 4637
NO: 404)

Segment cluster HSCOC4_PEA—1_node—80 (SEQ ID NO:462) according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15(SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 127 below describes the starting and ending position of this segment on each transcript.

TABLE 127
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4751 4844
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4896 4989
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5009 5102
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4817 4910
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4737 4830
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4435 4528
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4638 4731
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 5687 5780
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4638 4731
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5031 5124
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4638 4731
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5113 5206
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4638 4731
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4638 4731
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4638 4731
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4638 4731
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4638 4731
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4638 4731
NO: 404)

Segment cluster HSCOC4_PEA—1_node—82 (SEQ ID NO:463) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 128 below describes the starting and ending position of this segment on each transcript.

TABLE 128
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4845 4855
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 4990 5000
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5103 5113
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4911 4921
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4831 4841
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4529 4539
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4732 4742
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 5781 5791
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4732 4742
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5125 5135
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4732 4742
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5207 5217
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4732 4742
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4732 4742
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4732 4742
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4732 4742
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4732 4742
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4732 4742
NO: 404)

Segment cluster HSCOC4_PEA—1_node—83 (SEQ ID NO:464) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 129 below describes the starting and ending position of this segment on each transcript.

TABLE 129
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4856 4971
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5001 5116
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5114 5229
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 4922 5037
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4842 4957
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4540 4655
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4743 4858
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 5792 5907
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4743 4858
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5136 5251
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4743 4858
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5218 5333
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4743 4858
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4743 4858
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4743 4858
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4743 4858
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4743 4858
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4743 4858
NO: 404)

Segment cluster HSCOC4_PEA—1_node—84 (SEQ ID NO:465) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 130 below describes the starting and ending position of this segment on each transcript.

TABLE 130
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4972 4984
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5117 5129
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5230 5242
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5038 5050
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4958 4970
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4656 4668
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4859 4871
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 5908 5920
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4859 4871
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5252 5264
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4859 4871
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5334 5346
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4859 4871
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4859 4871
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4859 4871
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4859 4871
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4859 4871
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4859 4871
NO: 404)

Segment cluster HSCOC4_PEA—1_node—85 (SEQ ID NO:466) according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 131 below describes the starting and ending position of this segment on each transcript.

TABLE 131
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 4985 5031
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5130 5176
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5243 5289
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5051 5097
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 4971 5017
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4669 4715
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4872 4918
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 5921 5967
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 4872 4918
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5265 5311
NO: 396)
HSCOC4_PEA_1_T20 (SEQ ID 5347 5393
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4872 4918
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4872 4918
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4872 4918
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4872 4918
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4872 4918
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4872 4918
NO: 404)

Segment cluster HSCOC4_PEA—1_node—86 (SEQ ID NO:467) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T12 (SEQ ID NO:395). Table 132 below describes the starting and ending position of this segment on each transcript.

TABLE 132
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T12 (SEQ ID 4919 5032
NO: 395)

Segment cluster HSCOC4_PEA—1_node—87 (SEQ ID NO:468) according to the present invention is supported by 74 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404) . Table 133 below describes the starting and ending position of this segment on each transcript.

TABLE 133
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5032 5122
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5177 5267
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5290 5380
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5098 5188
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5018 5108
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4716 4806
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 4919 5009
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 5968 6058
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 5033 5123
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5312 5402
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4872 4962
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5394 5484
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 4919 5009
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 4919 5009
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 4919 5009
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 4919 5009
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 4919 5009
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 4919 5009
NO: 404)

Segment cluster HSCOC4_PEA—1_node—88 (SEQ ID NO:469) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T12 (SEQ ID NO:395). Table 134 below describes the starting and ending position of this segment on each transcript.

TABLE 134
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T12 (SEQ ID 5124 5213
NO: 395)

Segment cluster HSCOC4_PEA—1_node—89 (SEQ ID NO:470) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 135 below describes the starting and ending position of this segment on each transcript.

TABLE 135
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5123 5131
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5268 5276
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5381 5389
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5189 5197
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5109 5117
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4807 4815
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 5010 5018
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6059 6067
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 5214 5222
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5403 5411
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4963 4971
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5485 5493
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 5010 5018
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5010 5018
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5010 5018
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5010 5018
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5010 5018
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5010 5018
NO: 404)

Segment cluster HSCOC4_PEA—1_node—90 (SEQ ID NO:471) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 136 below describes the starting and ending position of this segment on each transcript.

TABLE 136
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5132 5142
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5277 5287
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5390 5400
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5198 5208
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5118 5128
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4816 4826
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 5019 5029
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6068 6078
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 5223 5233
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5412 5422
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4972 4982
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5494 5504
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 5019 5029
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5019 5029
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5019 5029
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5019 5029
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5019 5029
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5019 5029
NO: 404)

Segment cluster HSCOC4_PEA—1_node—91 (SEQ ID NO:472) according to the present invention is supported by 78 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 137 below describes the starting and ending position of this segment on each transcript.

TABLE 137
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5143 5179
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5288 5324
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5401 5437
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5209 5245
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5129 5165
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4827 4863
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 5030 5066
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6079 6115
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 5234 5270
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5423 5459
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 4983 5019
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5505 5541
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 5030 5066
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5030 5066
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5030 5066
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5030 5066
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5030 5066
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5030 5066
NO: 404)

Segment cluster HSCOC4_PEA—1_node—92 (SEQ ID NO:473) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404) . Table 138 below describes the starting and ending position of this segment on each transcript.

TABLE 138
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5180 5197
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5325 5342
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5438 5455
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5246 5263
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5166 5183
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4864 4881
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 5067 5084
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6116 6133
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 5271 5288
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5460 5477
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5020 5037
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5542 5559
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 5067 5084
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5067 5084
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5067 5084
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5067 5084
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5067 5084
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5067 5084
NO: 404)

Segment cluster HSCOC4_PEA—1_node—94 (SEQ ID NO:474) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T12 (SEQ ID NO:395) and HSCOC4_PEA—1_T21 (SEQ ID NO:399). Table 139 below describes the starting and ending position of this segment on each transcript.

TABLE 139
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T8 (SEQ ID 6567 6575
NO: 393)
HSCOC4_PEA_1_T12 (SEQ ID 6771 6779
NO: 395)
HSCOC4_PEA_1_T21 (SEQ ID 6567 6575
NO: 399)

Segment cluster HSCOC4_PEA—1_node—96 (SEQ ID NO:475) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 140 below describes the starting and ending position of this segment on each transcript.

TABLE 140
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5198 5205
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5343 5350
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5456 5463
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5264 5271
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5184 5191
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4882 4889
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6576 6583
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6134 6141
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 6780 6787
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5478 5485
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5038 5045
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5560 5567
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 6576 6583
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5085 5092
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5085 5092
NO: 401)
HSCOC4_PEA_1_T31 (SEQ ID 5085 5092
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5085 5092
NO: 404)

Segment cluster HSCOC4_PEA—1_node—97 (SEQ ID NO:476) according to the present invention can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 141 below describes the starting and ending position of this segment on each transcript.

TABLE 141
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5206 5222
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5351 5367
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5464 5480
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5272 5288
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5192 5208
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4890 4906
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6584 6600
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6142 6158
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 6788 6804
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5486 5502
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5046 5062
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5568 5584
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 6584 6600
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5093 5109
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5093 5109
NO: 401)
HSCOC4_PEA_1_T31 (SEQ ID 5093 5109
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5093 5109
NO: 404)

Segment cluster HSCOC4_PEA—1_node—98 (SEQ ID NO:477) according to the present invention is supported by 93 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 142 below describes the starting and ending position of this segment on each transcript.

TABLE 142
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5223 5271
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5368 5416
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5481 5529
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5289 5337
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5209 5257
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4907 4955
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6601 6649
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6159 6207
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 6805 6853
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5503 5551
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5063 5111
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5585 5633
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 6601 6649
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5110 5158
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5110 5158
NO: 401)
HSCOC4_PEA_1_T31 (SEQ ID 5110 5158
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5110 5158
NO: 404)

Segment cluster HSCOC4_PEA—1_node—99 (SEQ ID NO:478) according to the present invention is supported by 93 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 143 below describes the starting and ending position of this segment on each transcript.

TABLE 143
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5272 5300
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5417 5445
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5530 5558
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5338 5366
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5258 5286
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4956 4984
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6650 6678
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6208 6236
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 6854 6882
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5552 5580
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5112 5140
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5634 5662
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 6650 6678
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5159 5187
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5159 5187
NO: 401)
HSCOC4_PEA_1_T31 (SEQ ID 5159 5187
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5159 5187
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4197 4225
NO: 405)

Segment cluster HSCOC4_PEA—1_node—101 (SEQ ID NO:479) according to the present invention is supported by 116 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 144 below describes the starting and ending position of this segment on each transcript.

TABLE 144
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5301 5390
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5446 5535
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5559 5648
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5367 5456
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5287 5376
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 4985 5074
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6679 6768
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6237 6326
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 6883 6972
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5581 5670
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5141 5230
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5663 5752
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 6844 6933
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5188 5277
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5188 5277
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5085 5174
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5188 5277
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5188 5277
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4226 4315
NO: 405)

Segment cluster HSCOC4_PEA—1_node—102 (SEQ ID NO:480) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T31 (SEQ ID NO:403) and HSCOC4_PEA—1_T32 (SEQ ID NO:404). Table 145 below describes the starting and ending position of this segment on each transcript.

TABLE 145
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T31 (SEQ ID 5278 5362
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5278 5362
NO: 404)

Segment cluster HSCOC4_PEA—1_node—103 (SEQ ID NO:481) according to the present invention is supported by 106 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 146 below describes the starting and ending position of this segment on each transcript.

TABLE 146
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5391 5463
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5536 5608
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5649 5721
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5457 5529
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5377 5449
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5075 5147
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6769 6841
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6327 6399
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 6973 7045
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5671 5743
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5231 5303
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5753 5825
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 6934 7006
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5278 5350
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5278 5350
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5175 5247
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5363 5435
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5363 5435
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4316 4388
NO: 405)

Segment cluster HSCOC4_PEA—1_node—104 (SEQ ID NO:482) according to the present invention is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 147 below describes the starting and ending position of this segment on each transcript.

TABLE 147
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5464 5489
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5609 5634
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5722 5747
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5530 5555
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5450 5475
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5148 5173
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6842 6867
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6400 6425
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 7046 7071
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5744 5769
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5304 5329
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5826 5851
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 7007 7032
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5351 5376
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5351 5376
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5248 5273
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5436 5461
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5436 5461
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4389 4414
NO: 405)

Segment cluster HSCOC4_PEA—1_node—106 (SEQ ID NO:483) according to the present invention is supported by 110 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 148 below describes the starting and ending position of this segment on each transcript.

TABLE 148
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5490 5573
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 5635 5718
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 5748 5831
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5556 5639
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5476 5559
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5174 5257
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 6868 6951
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6426 6509
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 7072 7155
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 5770 5853
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5330 5413
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 5852 5935
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 7033 7116
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 5377 5460
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 5559 5642
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5274 5357
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5462 5545
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 5644 5727
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4415 4498
NO: 405)

Segment cluster HSCOC4_PEA—1_node—111 (SEQ ID NO:484) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSCOC4_PEA—1_T1 (SEQ ID NO:387), HSCOC4_PEA—1_T2 (SEQ ID NO:388), HSCOC4_PEA—1_T3 (SEQ ID NO:389), HSCOC4_PEA—1_T4 (SEQ ID NO:390), HSCOC4_PEA—1_T5 (SEQ ID NO:391), HSCOC4_PEA—1_T7 (SEQ ID NO:392), HSCOC4_PEA—1_T8 (SEQ ID NO:393), HSCOC4_PEA—1_T11 (SEQ ID NO:394), HSCOC4_PEA—1_T12 (SEQ ID NO:395), HSCOC4_PEA—1_T14 (SEQ ID NO:396), HSCOC4_PEA—1_T15 (SEQ ID NO:397), HSCOC4_PEA—1_T20 (SEQ ID NO:398), HSCOC4_PEA—1_T21 (SEQ ID NO:399), HSCOC4_PEA—1_T25 (SEQ ID NO:400), HSCOC4_PEA—1_T28 (SEQ ID NO:401), HSCOC4_PEA—1_T30 (SEQ ID NO:402), HSCOC4_PEA—1_T31 (SEQ ID NO:403), HSCOC4_PEA—1_T32 (SEQ ID NO:404) and HSCOC4_PEA—1_T40 (SEQ ID NO:405). Table 149 below describes the starting and ending position of this segment on each transcript.

TABLE 149
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
HSCOC4_PEA_1_T1 (SEQ ID 5857 5947
NO: 387)
HSCOC4_PEA_1_T2 (SEQ ID 6002 6092
NO: 388)
HSCOC4_PEA_1_T3 (SEQ ID 6115 6205
NO: 389)
HSCOC4_PEA_1_T4 (SEQ ID 5923 6013
NO: 390)
HSCOC4_PEA_1_T5 (SEQ ID 5843 5933
NO: 391)
HSCOC4_PEA_1_T7 (SEQ ID 5541 5631
NO: 392)
HSCOC4_PEA_1_T8 (SEQ ID 7235 7325
NO: 393)
HSCOC4_PEA_1_T11 (SEQ ID 6793 6883
NO: 394)
HSCOC4_PEA_1_T12 (SEQ ID 7439 7529
NO: 395)
HSCOC4_PEA_1_T14 (SEQ ID 6137 6227
NO: 396)
HSCOC4_PEA_1_T15 (SEQ ID 5697 5787
NO: 397)
HSCOC4_PEA_1_T20 (SEQ ID 6219 6309
NO: 398)
HSCOC4_PEA_1_T21 (SEQ ID 7400 7490
NO: 399)
HSCOC4_PEA_1_T25 (SEQ ID 6149 6239
NO: 400)
HSCOC4_PEA_1_T28 (SEQ ID 6331 6421
NO: 401)
HSCOC4_PEA_1_T30 (SEQ ID 5641 5731
NO: 402)
HSCOC4_PEA_1_T31 (SEQ ID 5829 5919
NO: 403)
HSCOC4_PEA_1_T32 (SEQ ID 6273 6363
NO: 404)
HSCOC4_PEA_1_T40 (SEQ ID 4782 4872
NO: 405)

Variant protein alignment to the previously known protein:

Sequence name: CO4_HUMAN (SEQ ID NO:485)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P3 (SEQ ID NO:488)×CO4_HUMAN (SEQ ID NO:485).

Alignment segment 1/1:

Quality: 8438.00
Escore: 0
Matching length: 870 Total length: 870
Matching Percent Similarity: 99.66 Matching Percent 99.66
Identity:
Total Percent Similarity: 99.66 Total Percent Identity: 99.66
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .
851 LRPVLYNYLDKNLTVRPHRS 870
|||||||||||||||  | |
851 LRPVLYNYLDKNLTVSVHVS 870

Sequence name: CO4_HUMAN (SEQ ID NO:485)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P5 (SEQ ID NO:489)×CO4_HUMAN (SEQ ID NO:485).

Alignment segment 1/1:

Quality: 7969.00
Escore: 0
Matching length: 818 Total length: 818
Matching Percent Similarity: 100.00 Matching Percent 100.00
Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DEVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNEEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLRLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .
801 DSLTTWEIHGLSLSKTKG 818
||||||||||||||||||
801 DSLTTWEIHGLSLSKTKG 818

Sequence name: CO4_HUMAN (SEQ ID NO:485)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P6 (SEQ ID NO:490)×CO4_HUMAN (SEQ ID NO:485).

Alignment segment 1/1:

Quality: 10211.00
Escore: 0
Matching length: 1052 Total length: 1052
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFETLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVEREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
1051 KG 1052
||
1051 KG 1052

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P12 (SEQ ID NO:491)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 13367.00
Escore: 0
Matching length: 1380 Total length: 1380
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKV 1380
||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKV 1380

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P15 (SEQ ID NO:492)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 13174.00
Escore: 0
Matching length: 1359 Total length: 1359
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGH0LFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLTQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
1351 IRGLEEELQ 1359
|||||||||
1351 IRGLEEELQ 1359

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P16 (SEQ ID NO:493)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 14137.00
Escore: 0
Matching length: 1457 Total length: 1457
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
1451 RRREAPK 1457
|||||||
1451 RRREAPK 1457

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P20 (SEQ ID NO:494)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 12641.00
Escore: 0
Matching length: 1303 Total length: 1303
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKCSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSEYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVEEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
1301 STQ 1303
|||
1301 STQ 1303

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P9 (SEQ ID NO:495)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 14831.00
Escore: 0
Matching length: 1529 Total length: 1529
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLTWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGRLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DRPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529
|||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P22 (SEQ ID NO:496)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 16066.00
Escore: 0
Matching length: 1654 Total length: 1654
Matching Percent 100.00 Matching Percent 99.94
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 99.94
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYTYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGTTDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWTASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .         .         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
||||||||||||||||||||||||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
         .         .         .         .         .
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600
||||||||||||||||||||||||||||||||||||||||||||||||||
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600
         .         .         .         .         .
1601 ALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAFRLFETKITQV 1650
||||||||||||||||||||||||||||||||||||||||||||||||||
1601 ALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAFRLFETKITQV 1650
1651 LHFS 1654
|||:
1651 LHFT 1654

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P23 (SEQ ID NO:497)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 15806.00
Escore: 0
Matching length: 1626 Total length: 1626
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSEFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPRPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDTPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .         .         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
||||||||||||||||||||||||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
         .         .         .         .         .
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600
||||||||||||||||||||||||||||||||||||||||||||||||||
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRR 1600
         .         .
1601 ALERGLQDEDGYRMKFACYYPRVEYG 1626
||||||||||||||||||||||||||
1601 ALERGLQDEDGYRMKFACYYPRVEYG 1626

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P24 (SEQ ID NO:498)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 14823.00
Escore: 0
Matching length: 1528 Total length: 1528
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLESPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDS 1528
||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDS 1528

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P25 (SEQ ID NO:499)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 15464.00
Escore: 0
Matching length: 1593 Total length: 1593
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGRLDEMQLDTQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .         .         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
||||||||||||||||||||||||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
         .         .         .         .
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593
|||||||||||||||||||||||||||||||||||||||||||
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P26 (SEQ ID NO:500)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 15464.00
Escore: 0
Matching length: 1593 Total length: 1593
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDCDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .         .         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
||||||||||||||||||||||||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQ 1550
         .         .         .         .
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593
|||||||||||||||||||||||||||||||||||||||||||
1551 PASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEG 1593

Sequence name: CO4_HUMAN_V3 (SEQ ID NO:487)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P30 (SEQ ID NO:501)×CO4_HUMAN_V3 (SEQ ID NO:487).

Alignment segment 1/1:

Quality: 11940.00
Escore: 0
Matching length: 1232 Total length: 1232
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGS 1232
||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGS 1232

Sequence name: CO4_HUMAN (SEQ ID NQ:485)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P38 (SEQ ID NO:502)×CO4_HUMAN (SEQ (SEQ ID NO:485).

Alignment segment 1/1:

Quality: 7969.00
Escore: 0
Matching length: 818 Total length: 818
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 300
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .
801 DSLTTWEIHGLSLSKTKG 818
||||||||||||||||||
801 DSLTTWEIHGLSLSKTKG 818

Sequence name: CO4_HUMAN (SEQ ID NO:485)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P39 (SEQ ID NO:503)×CO4_HUMAN (SEQ ID NO:485).

Alignment segment 1/1:

Quality: 3766.00
Escore: 0
Matching length: 387 Total length: 387
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alingment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ 387
|||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ 387

Sequence name: CO4_HUMAN (SEQ ID NO:485)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P40 (SEQ ID NO:504)×CO4_HUMAN (SEQ ID NO:485).

Alignment segment 1/1:

Quality: 2309.00
Escore: 0
Matching length: 236 Total length: 236
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY 236
||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY 236

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P41 (SEQ ID NO:505)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 14831.00
Escore: 0
Matching length: 1529 Total length: 1529
Matching Percent 100.00 Matching Percent 100.00
Similarity: Identity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPELLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPELLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYPVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVRVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQTEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQTEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD 1500
         .         .
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529
|||||||||||||||||||||||||||||
1501 LEKLTSLSDRYVSHFETEGPHVLLYFDSV 1529

Sequence name: CO4_HUMAN_V1 (SEQ ID NO:486)

Sequence documentation:

Alignment of: HSCOC4_PEA—1_P42 (SEQ ID NO:506)×CO4_HUMAN_V1 (SEQ ID NO:486).

Alignment segment 1/1:

Quality: 14480.00
Escore: 0
Matching length: 1506 Total length: 1544
Matching Percent 99.93 Matching Percent 99.87
Similarity: Identity:
Total Percent Similarity: 97.47 Total Percent Identity: 97.41
Gaps: 1

Alignment:

         .         .         .         .         .
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQ 50
         .         .         .         .         .
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 VVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLH 100
         .         .         .         .         .
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 QLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIY 150
         .         .         .         .         .
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 NPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQD 200
         .         .         .         .         .
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 DFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKP 250
         .         .         .         .         .
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 YILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE 300
         .         .         .         .         .
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGG 350
         .         .         .         .         .
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASG 400
         .         .         .         .         .
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 IPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSA 450
         .         .         .         .         .
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 GSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGA 500
         .         .         .         .         .
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 TFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHG 550
         .         .         .         .         .
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
||||||||||||||||||||||||||||||||||||||||||||||||||
551 DHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA 600
         .         .         .         .         .
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAA 650
         .         .         .         .         .
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
||||||||||||||||||||||||||||||||||||||||||||||||||
651 GLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAK 700
         .         .         .         .         .
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQEAESLRKKSRDKG 750
||||||||||||||||||||||||||||||||||||||||||||||||||
701 RCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQEAESLRKKSRDKG 750
         .         .         .         .         .
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
||||||||||||||||||||||||||||||||||||||||||||||||||
751 QAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLP 800
         .         .         .         .         .
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
||||||||||||||||||||||||||||||||||||||||||||||||||
801 DSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLE 850
         .         .         .         .         .
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
||||||||||||||||||||||||||||||||||||||||||||||||||
851 LRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS 900
         .         .         .         .         .
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
||||||||||||||||||||||||||||||||||||||||||||||||||
901 VVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNP 950
         .         .         .         .         .
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
||||||||||||||||||||||||||||||||||||||||||||||||||
951 LDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGV 1000
         .         .         .         .         .
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
||||||||||||||||||||||||||||||||||||||||||||||||||
1001 ASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQ 1050
         .         .         .         .         .
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
||||||||||||||||||||||||||||||||||||||||||||||||||
1051 KGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKL 1100
         .         .         .         .         .
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
||||||||||||||||||||||||||||||||||||||||||||||||||
1101 QETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALH 1150
         .         .         .         .         .
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||
1151 HGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL 1200
         .         .         .         .         .
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
1201 TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNP 1250
         .         .         .         .         .
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
||||||||||||||||||||||||||||||||||||||||||||||||||
1251 SDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFR 1300
         .         .         .         .         .
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
||||||||||||||||||||||||||||||||||||||||||||||||||
1301 STQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ 1350
         .         .         .         .         .
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
||||||||||||||||||||||||||||||||||||||||||||||||||
1351 IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIE 1400
         .         .         .         .         .
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
||||||||||||||||||||||||||||||||||||||||||||||||||
1401 VTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNR 1450
         .         .         .         .         .
1451 RRREAPKVVEEQESRVHYTVCIWWAPGAALGQGREGRTQAGAGLLEPAQA 1500
|||||||||||||||||||||||
1451 RRREAPKVVEEQESRVHYTVCIW........................... 1473
         .         .         .         .
1501 EPGRQLTRLHRRNGKVGLSGMAIADVTLLSGFHALRADLEKVWS 1544
           ||||||||||||||||||||||||||||||: |
1474 ...........RNGKVGLSGMAIADVTLLSGFHALRADLEKLTS 1506

DESCRIPTION FOR CLUSTER HUMTREFAC

Cluster HUMTREFAC features 2 transcript(s) and 7 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HUMTREFAC_PEA_2_T4 507
HUMTREFAC_PEA_2_T5 508

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HUMTREFAC_PEA_2_node_0 509
HUMTREFAC_PEA_2_node_9 510
HUMTREFAC_PEA_2_node_2 511
HUMTREFAC_PEA_2_node_3 512
HUMTREFAC_PEA_2_node_4 513
HUMTREFAC_PEA_2_node_5 514
HUMTREFAC_PEA_2_node_8 515

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
HUMTREFAC_PEA_2_P7 517 HUMTREFAC_PEA_2_T5
(SEQ ID NO: 508)
HUMTREFAC_PEA_2_P8 518 HUMTREFAC_PEA_2_T4
(SEQ ID NO: 507)

These sequences are variants of the known protein Trefoil factor 3 precursor (SwissProt accession identifier TFF3_HUMAN; known also according to the synonyms Intestinal trefoil factor; hP1.B), SEQ ID NO: 516, referred to herein as the previously known protein.

Protein Trefoil factor 3 precursor (SEQ ID NO:516) is known or believed to have the following function(s): May have a role in promoting cell migration (motogen). The sequence for protein Trefoil factor 3 precursor is given at the end of the application, as “Trefoil factor 3 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
74-76 QEA -> TRKT

Protein Trefoil factor 3 precursor (SEQ ID NO:516) localization is believed to be Secreted.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: defense response; digestion, which are annotation(s) related to Biological Process; and extracellular, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HUMTREFAC can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 36 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 36 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

TABLE 5
Normal tissue distribution
Name of Tissue Number
adrenal 40
colon 797
epithelial 95
general 39
liver 0
lung 57
lymph nodes 3
breast 0
muscle 3
pancreas 2
prostate 16
stomach 0
Thyroid 257
uterus 54

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 6.4e−01 6.9e−01 7.1e−01 1.1 7.8e−01 0.9
colon 4.6e−01 5.7e−01 9.7e−01 0.5 1 0.4
epithelial 2.4e−02 3.4e−01 9.5e−10 2.0 5.3e−02 1.1
general 2.5e−04 3.9e−02 1.4e−28 3.6 1.9e−10 1.9
liver 1 6.8e−01 1 1.0 6.9e−01 1.4
lung 4.8e−01 7.6e−01 2.2e−03 1.0 1.6e−01 0.5
lymph nodes 5.1e−01 8.0e−01 2.3e−02 5.0 1.9e−01 2.1
breast 7.6e−02 1.2e−01 3.1e−06 12.0 1.1e−03 6.5
muscle 9.2e−01 4.8e−01 1 0.8 3.9e−01 2.1
pancreas 1.2e−01 2.4e−01 5.7e−03 6.5 2.1e−02 4.6
prostate 1.5e−01 2.7e−01 9.9e−10 8.1 3.1e−07 5.7
stomach 3.0e−01 1.3e−01 5.0e−01 2.0 6.7e−02 2.8
Thyroid 6.4e−01 6.4e−01 9.6e−01 0.5 9.6e−01 0.5
uterus 4.1e−01 7.3e−01 7.5e−02 1.3 4.0e−01 0.8

As noted above, cluster HUMTREFAC features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Trefoil factor 3 precursor (SEQ ID NO:516). A description of each variant protein according to the present invention is now provided.

Variant protein HUMTREFAC_PEA—2_P7 (SEQ ID NO:517) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMTREFAC_PEA—2_P7 (SEQ ID NO:517) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMTREFAC_PEA—2_P7 (SEQ ID NO:517) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
5 A -> S No
5 A -> T No
14 A -> V Yes
43 L -> M No
60 P -> S Yes
123 S -> * Yes

Variant protein HUMTREFAC_PEA—2_P7 (SEQ ID NO:517) is encoded by the following transcript(s): HUMTREFAC_PEA—2_T5 (SEQ ID NO:508), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMTREFAC_PEA—2_T5 (SEQ ID NO:508) is shown in bold; this coding portion starts at position 278 and ends at position 688. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMTREFAC_PEA—2_P7 (SEQ ID NO:517) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
233 A -> G Yes
290 G -> A No
290 G -> T No
318 C -> T Yes
404 C -> A No
404 C -> T No
455 C -> T Yes
645 C -> A Yes
685 C -> T No

Variant protein HUMTREFAC_PEA—2_P8 (SEQ ID NO:518) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMTREFAC_PEA—2_T4 (SEQ ID NO:507). An alignment is given to the known protein (Trefoil factor 3 precursor (SEQ ID NO:516)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMTREFAC_PEA—2_P8 (SEQ ID NO:518) and TFF3_HUMAN (SEQ ID NO:516):

1.An isolated chimeric polypeptide encoding for HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), comprising a first amino acid sequence being at least 90% homologous to MAARALCMLGLVLALLSSSSAEEYVGL corresponding to amino acids 1-27 of TFF3_HUMAN (SEQ ID NO:516), which also corresponds to amino acids 1-27 of HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WKVHLPKGEGFSSG (SEQ ID NO:996) corresponding to amino acids 28-41 of HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of HUMTREFAC_PEA—2_P8 (SEQ ID NO:518), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WKVHLPKGEGFSSG (SEQ ID NO:996) in HUMTREFAC_PEA—2_P8 (SEQ ID NO:518).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMTREFAC_PEA—2_P8 (SEQ ID NO:518) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMTREFAC_PEA—2_P8 (SEQ ID NO:518) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
5 A -> S No
5 A -> T No
14 A -> V Yes

Variant protein HUMTREFAC_PEA—2_P8 (SEQ ID NO:518) is encoded by the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) is shown in bold; this coding portion starts at position 278 and ends at position 400. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMTREFAC_PEA—2_P8 (SEQ ID NO:518) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
233 A -> G Yes
290 G -> A No
290 G -> T No
318 C -> T Yes
515 C -> A No
515 C -> T No
566 C -> T Yes
756 C -> A Yes
796 C -> T No
1265 A -> C No
1266 A -> T No

As noted above, cluster HUMTREFAC features 7 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMTREFAC_PEA—2_node—0 (SEQ ID NO:509) according to the present invention is supported by 188 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) and HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
HUMTREFAC_PEA_2_T4 (SEQ ID 1 359
NO: 507)
HUMTREFAC_PEA_2_T5 (SEQ ID 1 359
NO: 508)

Segment cluster HUMTREFAC_PEA—2_node—9 (SEQ ID NO:510) according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) and HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
HUMTREFAC_PEA_2_T4 (SEQ ID 681 1266
NO: 507)
HUMTREFAC_PEA_2_T5 (SEQ ID 570 747
NO: 508)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HUMTREFAC_PEA—2_node—2 (SEQ ID NO:511) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
HUMTREFAC_PEA_2_T4 (SEQ ID 360 470
NO: 507)

Segment cluster HUMTREFAC_PEA—2_node—3 (SEQ ID NO:512) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) and HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
HUMTREFAC_PEA_2_T4 (SEQ ID 471 514
NO: 507)
HUMTREFAC_PEA_2_T5 (SEQ ID 360 403
NO: 508)

Segment cluster HUMTREFAC_PEA—2_node—4 (SEQ ID NO:513) according to the present invention is supported by 197 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) and HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID 515 611
NO: 507)
HUMTREFAC_PEA_2_T5 (SEQ ID 404 500
NO: 508)

Segment cluster HUMTREFAC_PEA—2_node—5 (SEQ ID NO:514) according to the present invention is supported by 187 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) and HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID 612 661
NO: 507)
HUMTREFAC_PEA_2_T5 (SEQ ID 501 550
NO: 508)

Segment cluster HUMTREFAC_PEA—2_node—8 (SEQ ID NO:515) according to the present invention can be found in the following transcript(s): HUMTREFAC_PEA—2_T4 (SEQ ID NO:507) and HUMTREFAC_PEA—2_T5 (SEQ ID NO:508). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID 662 680
NO: 507)
HUMTREFAC_PEA_2_T5 (SEQ ID 551 569
NO: 508)

Variant protein alignment to the previously known protein:

Sequence name: TFF3_HUMAN (SEQ ID NO:516)

Sequence documentation:

Alignment of: HUMTREFAC_PEA—2_P8 (SEQ ID NO:518)×TFF3_HUMAN (SEQ ID NO:516).

Alignment segment 1/1:

Quality: 246.00
Escore: 0
Matching length: 27 Total length: 27
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .
1 MAARALCMLGLVLALLSSSSAEEYVGL 27
|||||||||||||||||||||||||||
1 MAARALCMLGLVLALLSSSSAEEYVGL 27

DESCRIPTION FOR CLUSTER HUMOSTRO

Cluster HUMOSTRO features 3 transcript(s) and 30 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HUMOSTRO_PEA_1_PEA_1_T14 519
HUMOSTRO_PEA_1_PEA_1_T16 520
HUMOSTRO_PEA_1_PEA_1_T30 521

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HUMOSTRO_PEA_1_PEA_1_node_0 522
HUMOSTRO_PEA_1_PEA_1_node_10 523
HUMOSTRO_PEA_1_PEA_1_node_16 524
HUMOSTRO_PEA_1_PEA_1_node_23 525
HUMOSTRO_PEA_1_PEA_1_node_31 526
HUMOSTRO_PEA_1_PEA_1_node_43 527
HUMOSTRO_PEA_1_PEA_1_node_3 528
HUMOSTRO_PEA_1_PEA_1_node_5 529
HUMOSTRO_PEA_1_PEA_1_node_7 530
HUMOSTRO_PEA_1_PEA_1_node_8 531
HUMOSTRO_PEA_1_PEA_1_node_15 532
HUMOSTRO_PEA_1_PEA_1_node_17 533
HUMOSTRO_PEA_1_PEA_1_node_20 534
HUMOSTRO_PEA_1_PEA_1_node_21 535
HUMOSTRO_PEA_1_PEA_1_node_22 536
HUMOSTRO_PEA_1_PEA_1_node_24 537
HUMOSTRO_PEA_1_PEA_1_node_26 538
HUMOSTRO_PEA_1_PEA_1_node_27 539
HUMOSTRO_PEA_1_PEA_1_node_28 540
HUMOSTRO_PEA_1_PEA_1_node_29 541
HUMOSTRO_PEA_1_PEA_1_node_30 542
HUMOSTRO_PEA_1_PEA_1_node_32 543
HUMOSTRO_PEA_1_PEA_1_node_34 544
HUMOSTRO_PEA_1_PEA_1_node_36 545
HUMOSTRO_PEA_1_PEA_1_node_37 546
HUMOSTRO_PEA_1_PEA_1_node_38 547
HUMOSTRO_PEA_1_PEA_1_node_39 548
HUMOSTRO_PEA_1_PEA_1_node_40 549
HUMOSTRO_PEA_1_PEA_1_node_41 550
HUMOSTRO_PEA_1_PEA_1_node_42 551

TABLE 3
Proteins of interest
Sequence Corresponding
Protein Name ID No. Transcript(s)
HUMOSTRO_PEA_1_PEA_1_P21 553 HUMOSTRO_PEA_1_PEA_1_T14
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_P25 554 HUMOSTRO_PEA_1_PEA_1_T16
(SEQ ID NO:520)
HUMOSTRO_PEA_1_PEA_1_P30 555 HUMOSTRO_PEA_1_PEA_1_T30
(SEQ ID NO:521)

These sequences are variants of the known protein Osteopontin precursor (SwissProt accession identifier OSTP_HUMAN; known also according to the synonyms Bone sialoprotein 1; Urinary stone protein; Secreted phosphoprotein 1; SPP-1; Nephropontin; Uropontin), SEQ ID NO: 552, referred to herein as the previously known protein.

Protein Osteopontin precursor (SEQ ID NO:552) is known or believed to have the following function(s): Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction;Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity (By similarity). The sequence for protein Osteopontin precursor (SEQ ID NO:552) is given at the end of the application, as “Osteopontin precursor (SEQ ID NO:552) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
301 R -> H (in dbSNP: 4660). /FTId = VAR_014717.
188 D -> H
237 T -> A
275-278 SHEF -> GNSL

Protein Osteopontin precursor (SEQ ID NO:552) localization is believed to be Secreted.

The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Regeneration, bone. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Bone formation stimulant. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Musculoskeletal.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: ossification; anti-apoptosis; inflammatory response; cell-matrix adhesion; cell-cell signaling, which are annotation(s) related to Biological Process; defense/immunity protein; cytokine; integrin ligand; protein binding; growth factor; apoptosis inhibitor, which are annotation(s) related to Molecular Function; and extracellular matrix, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HUMOSTRO can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 37 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 37 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors, breast malignant tumors, ovarian carcinoma and skin malignancies.

TABLE 5
Normal tissue distribution
Name of Tissue Number
adrenal 4
bladder 0
bone 897
brain 506
colon 69
epithelial 548
general 484
head and neck 50
kidney 5618
liver 4
lung 10
lymph nodes 75
breast 8
bone marrow 62
muscle 37
ovary 40
pancreas 845
prostate 48
skin 13
stomach 73
Thyroid 0
uterus 168

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 1.5e−01 2.1e−01 2.0e−02 4.6 4.4e−02 3.6
bladder 1.2e−01 9.2e−02 5.7e−02 4.1 2.1e−02 4.3
bone 4.9e−01 7.4e−01 4.1e−06 0.6 5.4e−01 0.4
brain 6.6e−01 7.0e−01 3.2e−01 0.6 1 0.4
colon 2.7e−01 4.0e−01 3.1e−01 1.5 5.2e−01 1.1
epithelial 2.0e−07 1.6e−03 9.8e−01 0.7 1 0.5
general 1.2e−06 1.2e−02 7.9e−01 0.8 1 0.6
head and neck 3.4e−01 5.0e−01 1 0.7 1 0.7
kidney 6.8e−01 7.4e−01 1 0.2 1 0.1
liver 3.3e−01 2.5e−01 1 1.8 2.3e−01 2.6
lung 4.3e−04 4.6e−03 2.1e−30 15.0 2.8e−27 23.5
lymph nodes 6.7e−01 8.7e−01 8.1e−01 0.7 9.9e−01 0.3
breast 2.3e−01 3.0e−01 1.9e−04 6.2 4.1e−03 4.3
bone marrow 7.5e−01 7.8e−01 1 0.3 2.0e−02 1.2
muscle 4.0e−02 7.5e−02 1.1e−01 4.6 5.1e−01 1.5
ovary 4.7e−02 8.4e−02 1.9e−05 5.4 8.3e−04 3.7
pancreas 5.0e−02 3.3e−01 1 0.3 1 0.2
prostate 8.5e−01 9.0e−01 8.9e−01 0.7 9.5e−01 0.6
skin 1.6e−01 1.6e−01 1.2e−10 12.6 5.2e−04 4.1
stomach 1.5e−01 6.3e−01 5.0e−01 1.2 9.4e−01 0.6
Thyroid 2.9e−01 2.9e−01 5.9e−02 2.0 5.9e−02 2.0
uterus 6.1e−02 5.7e−01 1.1e−01 1.3 7.0e−01 0.7

As noted above, cluster HUMOSTRO features 3 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Osteopontin precursor (SEQ ID NO:552). A description of each variant protein according to the present invention is now provided.

Variant protein HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519). An alignment is given to the known protein (Osteopontin precursor (SEQ ID NO:552)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553) and OSTP_HUMAN (SEQ ID NO:552):

1.An isolated chimeric polypeptide encoding for HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), comprising a first amino acid sequence being at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ corresponding to amino acids 1-58 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-58 of HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VFLNFS (SEQ ID NO:997) corresponding to amino acids 59-64 of HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VFLNFS (SEQ ID NO:997) in HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because of manual inspection of known protein localization and/or gene structure.

Variant protein HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
7 C -> W No
31 Q -> R No
47 D -> V Yes
49 S -> P No

The glycosylation sites of variant protein HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553), as compared to the known protein Osteopontin precursor (SEQ ID NO:552), are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 8
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
79 no
106 no

Variant protein HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553) is encoded by the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) is shown in bold; this coding portion starts at position 199 and ends at position 390. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
136 A -> G Yes
154 T -> No
159 G -> T Yes
219 C -> G No
274 -> G No
290 A -> G No
338 A -> T Yes
343 T -> C No
413 G -> C Yes
707 C -> T Yes
708 C -> A Yes
715 A -> G Yes
730 A -> C No
730 A -> G No
746 T -> C Yes
767 C -> T No
779 G -> A Yes
866 -> G No
869 T -> No
889 -> A No
891 A -> C No
891 A -> G No
905 T -> C No
910 -> G No
910 -> T No
997 A -> G No
1026 G -> C No
1042 -> G No
1042 -> T No
1071 A -> No
1071 A -> C No
1098 A -> No
1105 C -> T No
1124 -> G No
1135 G -> A Yes
1136 T -> No
1136 T -> G No
1173 A -> C No
1173 A -> G No
1179 A -> G No
1214 C -> T Yes
1246 T -> No
1246 T -> A No
1359 A -> No
1359 A -> G No
1362 T -> No
1365 C -> T Yes
1366 G -> A Yes
1408 A -> C No
1418 A -> C No
1433 A -> C No
1456 A -> C No
1524 T -> A No
1524 T -> C No
1547 A -> G Yes
1553 T -> No
1574 -> G No
1654 A -> C Yes
1691 A -> G No
1703 A -> C Yes
1755 A -> C No
1764 T -> No

Variant protein HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). An alignment is given to the known protein (Osteopontin precursor (SEQ ID NO:552) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554) and OSTP_HUMAN (SEQ ID NO:552):

1.An isolated chimeric polypeptide encoding for HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), comprising a first amino acid sequence being at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-31 of HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence H corresponding to amino acids 32-32 of HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
7 C -> W No
31 Q -> R No

The glycosylation sites of variant protein HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554), as compared to the known protein Osteopontin precursor (SEQ ID NO:552), are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 11
Glycosylation site(s)
Position(s) on known Present in Position
amino acid sequence variant protein? in variant protein?
79 no
106 no

Variant protein HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554) is encoded by the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520) is shown in bold; this coding portion starts at position 199 and ends at position 294. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
136 A -> G Yes
154 T -> No
159 G -> T Yes
219 C -> G No
274 -> G No
290 A -> G No
419 C -> T Yes
454 G -> C Yes
527 A -> T Yes
532 T -> C No
630 C -> T Yes
631 C -> A Yes
638 A -> G Yes
653 A -> C No
653 A -> G No
669 T -> C Yes
690 C -> T No
702 G -> A Yes
789 -> G No
792 T -> No
812 -> A No
814 A -> C No
814 A -> G No
828 T -> C No
833 -> G No
833 -> T No
920 A -> G No
949 G -> C No
965 -> G No
965 -> T No
994 A -> No
994 A -> C No
1021 A -> No
1028 C -> T No
1047 -> G No
1058 G -> A Yes
1059 T -> No
1059 T -> G No
1096 A -> C No
1096 A -> G No
1102 A -> G No
1137 C -> T Yes
1169 T -> No
1169 T -> A No
1282 A -> No
1282 A -> G No
1285 T -> No
1288 C -> T Yes
1289 G -> A Yes
1331 A -> C No
1341 A -> C No
1356 A -> C No
1379 A -> C No
1447 T -> A No
1447 T -> C No
1470 A -> G Yes
1476 T -> No
1497 -> G No
1577 A -> C Yes
1614 A -> G No
1626 A -> C Yes
1678 A -> C No
1687 T -> No

Variant protein HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521). An alignment is given to the known protein (Osteopontin precursor (SEQ ID NO:552) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555) and OSTP_HUMAN (SEQ ID NO:552):

1.An isolated chimeric polypeptide encoding for HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-31 of HYMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSIFYVFI (SEQ ID NO:998) corresponding to amino acids 32-39 of HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSIFYVFI (SEQ ID NO:998) in HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
7 C -> W No
31 Q -> R No

The glycosylation sites of variant protein HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555), as compared to the known protein Osteopontin precursor (SEQ ID NO:552), are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 14
Glycosylation site(s)
Position(s) on known
amino acid sequence Present in variant protein?
79 no
106 no

Variant protein HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555) is encoded by the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521) is shown in bold; this coding portion starts at position 199 and ends at position 315. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
136 A -> G Yes
154 T -> No
159 G -> T Yes
219 C -> G No
274 -> G No
290 A -> G No

As noted above, cluster HUMOSTRO features 30 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—0 (SEQ ID NO:522) according to the present invention is supported by 333 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519), HUMOSTRO_PEA—1_PEA—1T16 (SEQ ID NO:520) and HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1 184
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1 184
(SEQ ID NO:520)
HUMOSTRO_PEA_1_PEA_1_T30 1 184
(SEQ ID NO:521)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—10 (SEQ ID NO:523) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T16 292 480
(SEQ ID NO: 520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—16 (SEQ ID NO:524) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 373 638
(SEQ ID NO:519)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—23 (SEQ ID NO:525) according to the present invention is supported by 334 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 804 967
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 727 890
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—31 (SEQ ID NO:526) according to the present invention is supported by 350 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1164 1393
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1087 1316
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—43 (SEQ ID NO:527) according to the present invention is supported by 192 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1810 1846
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1733 1769
(SEQ ID NO:520)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—3 (SEQ ID NO:528) according to the present invention is supported by 353 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14(SEQ ID NO:519), HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520) and HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 185 210
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 185 210
(SEQ ID NO:520)
HUMOSTRO_PEA_1_PEA_1_T30 185 210
(SEQ ID NO:521)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—5 (SEQ ID NO:529) according to the present invention is supported by 353 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519), HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520) and HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 211 252
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 211 252
(SEQ ID NO:520)
HUMOSTRO_PEA_1_PEA_1_T30 211 252
(SEQ ID NO:521)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—7 (SEQ ID NO:530) according to the present invention is supported by 357 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519), HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520) and HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 253 291
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 253 291
(SEQ ID NO:520)
HUMOSTRO_PEA_1_PEA_1_T30 253 291
(SEQ ID NO:521)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—8 (SEQ ID NO:531) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T30 (SEQ ID NO:521). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T30 292 378
(SEQ ID NO:521)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—15 (SEQ ID NO:532) according to the present invention is supported by 366 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 292 372
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 481 561
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—17 (SEQ ID NO:533) according to the present invention is supported by 261 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 639 680
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 562 603
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—20 (SEQ ID NO:534) according to the present invention can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 681 688
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 604 611
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—21 (SEQ ID NO:535) according to the present invention is supported by 315 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 689 738
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 612 661
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—22 (SEQ ID NO:536) according to the present invention is supported by 322 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 739 803
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 662 726
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—24 (SEQ ID NO:537) according to the present invention is supported by 270 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 968 1004
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 891 927
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—26 (SEQ ID NO:538) according to the present invention can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1005 1022
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 928 945
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—27 (SEQ ID NO:539) according to the present invention is supported by 260 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1023 1048
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 946 971
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—28 (SEQ ID NO:540) according to the present invention is supported by 273 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1049 1100
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 972 1023
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—29 (SEQ ID NO:541) according to the present invention is supported by 272 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1101 1151
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1024 1074
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—30 (SEQ ID NO:542) according to the present invention can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1152 1163
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1075 1086
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—32 (SEQ ID NO:543) according to the present invention is supported by 293 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1394 1427
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1317 1350
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—34 (SEQ ID NO:544) according to the present invention is supported by 301 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1428 1468
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1351 1391
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—36 (SEQ ID NO:545) according to the present invention is supported by 292 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1469 1504
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1392 1427
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—37 (SEQ ID NO:546) according to the present invention is supported by 295 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1505 1623
(SEQ ID NO 519)
HUMOSTRO_PEA_1_PEA_1_T16 1428 1546
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—38 (SEQ ID NO:547) according to the present invention can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1624 1634
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1547 1557
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—39 (SEQ ID NO:548) according to the present invention is supported by 268 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1635 1725
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1558 1648
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—40 (SEQ ID NO:549) according to the present invention can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1726 1743
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1649 1666
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—41 (SEQ ID NO:550) according to the present invention can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1744 1749
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1667 1672
(SEQ ID NO:520)

Segment cluster HUMOSTRO_PEA—1_PEA—1_node—42 (SEQ ID NO:551) according to the present invention is supported by 224 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMOSTRO_PEA—1_PEA—1_T14 (SEQ ID NO:519) and HUMOSTRO_PEA—1_PEA—1_T16 (SEQ ID NO:520). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HUMOSTRO_PEA_1_PEA_1_T14 1750 1809
(SEQ ID NO:519)
HUMOSTRO_PEA_1_PEA_1_T16 1673 1732
(SEQ ID NO:520)

Variant protein alignment to the previously known protein:

Sequence name: OSTP_HUMAN (SEQ ID NO:552)

Sequence documentation:

Alignment of: HUMOSTRO_PEA—1_PEA—1_P21 (SEQ ID NO:553)×OSTP HUMAN (SEQ ID NO:552).

Alignment segment 1/1:

Quality: 578.00
Escore: 0
Matching length: 58 Total length: 58
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQ 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQ 50
51 KQNLLAPQ 58
||||||||
51 KQNLLAPQ 58

Sequence name: OSTP_HUMAN (SEQ ID NO:552)

Sequence documentation:

Alignment of: HUMOSTRO_PEA—1_PEA—1_P25 (SEQ ID NO:554)×OSTP_HUMAN (SEQ ID NO:552).

Alignment segment 1/1:

Quality: 301.00
Escore: 0
Matching length: 31 Total length: 31
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·
1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31
|||||||||||||||||||||||||||||||
1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31

Sequence name: OSTP_HUMAN (SEQ ID NO:552)

Sequence documentation:

Alignment of: HUMOSTRO_PEA—1_PEA—1_P30 (SEQ ID NO:555)×OSTP_HUMAN (SEQ ID NO:552).

Alignment segment 1/1:

Quality: 301.00
Escore: 0
Matching length: 31 Total length: 31
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·
1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31
|||||||||||||||||||||||||||||||
1 MRIAVICFCLLGITCAIPVKQADSGSSEEKQ 31

Description for Cluster R11723

Cluster R11723 features 6 transcript(s) and 26 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
R11723_PEA_1_T15 556
R11723_PEA_1_T17 557
R11723_PEA_1_T19 558
R11723_PEA_1_T20 559
R11723_PEA_1_T5 560
R11723_PEA_1_T6 561

TABLE 2
Segments of interest
Segment Name Sequence ID No.
R11723_PEA_1_node_13 562
R11723_PEA_1_node_16 563
R11723_PEA_1_node_19 564
R11723_PEA_1_node_2 565
R11723_PEA_1_node_22 566
R11723_PEA_1_node_31 567
R11723_PEA_1_node_10 568
R11723_PEA_1_node_11 569
R11723_PEA_1_node_15 570
R11723_PEA_1_node_18 571
R11723_PEA_1_node_20 572
R11723_PEA_1_node_21 573
R11723_PEA_1_node_23 574
R11723_PEA_1_node_24 575
R11723_PEA_1_node_25 576
R11723_PEA_1_node_26 577
R11723_PEA_1_node_27 578
R11723_PEA_1_node_28 579
R11723_PEA_1_node_29 580
R11723_PEA_1_node_3 581
R11723_PEA_1_node_30 582
R11723_PEA_1_node_4 583
R11723_PEA_1_node_5 584
R11723_PEA_1_node_6 585
R11723_PEA_1_node_7 586
R11723_PEA_1_node_8 587

TABLE 3
Proteins of interest
Protein Name Sequence ID No.
R11723_PEA_1_P2 588
R11723_PEA_1_P6 589
R11723_PEA_1_P7 590
R11723_PEA_1_P13 591
R11723_PEA_1_P10 592

Cluster R11723 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of FIG. 38 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 38 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors.

TABLE 4
Normal tissue distribution
Name of Tissue Number
adrenal 0
brain 30
epithelial 3
general 17
head and neck 0
kidney 0
lung 0
breast 0
ovary 0
pancreas 10
skin 0
uterus 0

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 4.2e−01 4.6e−01 4.6e−01 2.2 5.3e−01 1.9
brain 2.2e−01 2.0e−01 1.2e−02 2.8 5.0e−02 2.0
epithelial 3.0e−05 6.3e−05 1.8e−05 6.3 3.4e−06 6.4
general 7.2e−03 4.0e−02 1.3e−04 2.1 1.1e−03 1.7
head and neck 1 5.0e−01 1 1.0 7.5e−01 1.3
kidney 1.5e−01 2.4e−01 4.4e−03 5.4 2.8e−02 3.6
lung 1.2e−01 1.6e−01 1 1.6 1 1.3
breast 5.9e−01 4.4e−01 1 1.1 6.8e−01 1.5
ovary 1.6e−02 1.3e−02 1.0e−01 3.8 7.0e−02 3.5
pancreas 5.5e−01 2.0e−01 3.9e−01 1.9 1.4e−01 2.7
skin 1 4.4e−01 1 1.0 1.9e−02 2.1
uterus 1.5e−02 5.4e−02 1.9e−01 3.1 1.4e−01 2.5

As noted above, cluster R11723 features 6 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein R11723_PEA—1_P2 (SEQ ID NO:588) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA—1_T6 (SEQ ID NO:561). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R11723_PEA—1_P2 (SEQ ID NO:588) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P2 (SEQ ID NO:588) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
107 H -> P Yes
70 G -> No
70 G -> C No

Variant protein R11723_PEA—1_P2 (SEQ ID NO:588) is encoded by the following transcript(s): R11723_PEA—1_T6 (SEQ ID NO:561), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA—1_T6 (SEQ ID NO:561) is shown in bold; this coding portion starts at position 1716 and ends at position 2051. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P2 (SEQ ID NO:588) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
1231 C -> T Yes
1278 G -> C Yes
1923 G -> No
1923 G -> T No
2035 A -> C Yes
2048 A -> C No
2057 A -> G Yes

Variant protein R11723_PEA—1_P6 (SEQ ID NO:589) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA—1_T15 (SEQ ID NO:556). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between R11723_PEA—1_P6 (SEQ ID NO:589) and Q8IXM0 (SEQ ID NO:885):

1 . An isolated chimeric polypeptide encoding for R11723_PEA—1_P6 (SEQ ID NO:589), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEJQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR (SEQ ID NO:1022) corresponding to amino acids 1-110 of R11723_PEA—1_P6 (SEQ ID NO:589), and a second amino acid sequence being at least 90% homologous to MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHV RPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 1-112 of Q8IXM0, which also corresponds to amino acids 111-222 of R11723_PEA—1_P6 (SEQ ID NO:589), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R11723_PEA—1_P6 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV (SEQ ID NO:1022)
MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR
of R11723_PEA_1_P6. (SEQ ID NO:589)

Comparison report between R11723_PEA—1_P6 (SEQ ID NO:589) and Q96AC2 (SEQ ID NO:886):

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P6 (SEQ ID NO:589), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 1-83 of Q96AC2 (SEQ ID NO: 886), which also corresponds to amino acids 1-83 of R11723_PEA—1_P6 (SEQ ID NO:589), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ (SEQ ID NO: 1023) corresponding to amino acids 84-222 of R11723_PEA—1_P6 (SEQ ID NO:589), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P6 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL (SEQ ID NO:1023)
RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ
CHNNQPWADTSRRERQRKEKHSMRTQ
in R11723_PEA_1_P6. (SEQ ID NO:589)

Comparison report between R11723_PEA—1_P6 (SEQ ID NO:589) and Q8N2G4 (SEQ ID NO:887):

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P6 (SEQ ID NO:589), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 1-83 of Q8N2G4, which also corresponds to amino acids 1-83 of R11723_PEA—1_P6 (SEQ ID NO:589), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ (SEQ ID NO:1023) corresponding to amino acids 84-222 of R11723_PEA—1_P6 (SEQ ID NO:589), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P6 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL (SEQ ID NO:1023)
RGHRVQERVDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ
CHNNQPWADTSRRERQRKEKHSMRTQ
in R11723_PEA_1_P6. (SEQ ID NO:589)

Comparison report between R11723_PEA—1_P6 (SEQ ID NO:589) and BAC85518 (SEQ ID NO:888):

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P6 (SEQ ID NO:589), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 24-106 of BAC85518, which also corresponds to amino acids 1-83 of R11723_PEA—1_P6 (SEQ ID NO:589), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ (SEQ ID NO:1023) corresponding to amino acids 84-222 of R11723_PEA—1_P6 (SEQ ID NO:589), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P6 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL (SEQ ID NO:1023)
RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ
CHNNQPWADTSRRERQRKEKHSMRTQ
in R11723_PEA_1_P6. (SEQ ID NO:589)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R11723_PEA—1_P6 (SEQ ID NO:589) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P6 (SEQ ID NO:589) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
180 G -> No
180 G -> C No
217 H -> P Yes

Variant protein R11723_PEA—1_P6 (SEQ ID NO:589) is encoded by the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA—1_T15 (SEQ ID NO:556) is shown in bold; this coding portion starts at position 434 and ends at position 1099. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P6 (SEQ ID NO:589) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
971 G -> No
971 G -> T No
1083 A -> C Yes
1096 A -> C No
1105 A -> G Yes

Variant protein R11723_PEA—1_P7 (SEQ ID NO:590) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA—1_T17 (SEQ ID NO:557). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between R11723_PEA—1_P7 (SEQ ID NO:590) and Q96AC2 (SEQ ID NO: 886):

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 1-64 of Q96AC2 (SEQ ID NO: 886), which also corresponds to amino acids 1-64 of R11723_PEA—1_P7 (SEQ ID NO:590), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) corresponding to amino acids 65-93 of R11723_PEA—1_P7 (SEQ ID NO:590), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) in R11723_PEA—1_P7 (SEQ ID NO:590).

Comparison report between R11723_PEA—1_P7 (SEQ ID NO:590) and Q8N2G4:

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 1-64 of Q8N2G4, which also corresponds to amino acids 1-64 of R11723_PEA—1_P7 (SEQ ID NO:590), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) corresponding to amino acids 65-93 of R11723_PEA—1_P7 (SEQ ID NO:590), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) in R11723_PEA—1_P7 (SEQ ID NO:590).

Comparison report between R11723_PEA—1_P7 (SEQ ID NO:590) and BAC85273:

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG (SEQ ID NO:1025) corresponding to amino acids 1-5 of R11723_PEA—1_P7 (SEQ ID NO:590), second amino acid sequence being at least 90% homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG corresponding to amino acids 22-80 of BAC85273, which also corresponds to amino acids 6-64 of R11723_PEA—1_P7 (SEQ ID NO:590), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) corresponding to amino acids 65-93 of R11723_PEA—1_P7 (SEQ ID NO:590), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R11723_PEA—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG (SEQ ID NO:1025) of R11723_PEA—1_P7 (SEQ ID NO:590).

3. An isolated polypeptide encoding for a tail of R11723_PEA—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) in R11723_PEA—1_P7 (SEQ ID NO:590).

Comparison report between R11723_PEA—1_P7 (SEQ ID NO:590) and BAC85518:

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 24-87 of BAC85518, which also corresponds to amino acids 1-64 of R11723_PEA—1_P7 (SEQ ID NO:590), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) corresponding to amino acids 65-93 of R11723_PEA—1_P7 (SEQ ID NO:590), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1024) in R11723_PEA—1_P7 (SEQ ID NO:590).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R11723_PEA—1_P7 (SEQ ID NO:590) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P7 (SEQ ID NO:590) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
67 C -> S Yes

Variant protein R11723_PEA—1_P7 (SEQ ID NO:590) is encoded by the following transcript(s): R11723_PEA—1_T17 (SEQ ID NO:557), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA—1_T17 (SEQ ID NO:557) is shown in bold; this coding portion starts at position 434 and ends at position 712. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P7 (SEQ ID NO:590) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
625 G -> T Yes
633 G -> C Yes
1303 C -> T Yes

Variant protein R11723_PEA—1_P13 (SEQ ID NO:591) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA—1_T19 (SEQ ID NO:558). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between R11723_PEA—1_P13 (SEQ ID NO:591) and Q96AC2 (SEQ ID NO: 886):

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P13 (SEQ ID NO:591) comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO: 886), which also corresponds to amino acids 1-63 of R11723_PEA—1_P13 (SEQ ID NO:591), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) corresponding to amino acids 64-84 of R11723_PEA—1_P13 (SEQ ID NO:591), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R1723_PEA—1_P13 (SEQ ID NO:591), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) in R11723_PEA—1_P13 (SEQ ID NO:591).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R11723_PEA—1_P13 (SEQ ID NO:591) is encoded by the following transcript(s): R11723_PEA—1_T19 (SEQ ID NO:558) and R11723_PEA—1_T5 (SEQ ID NO:560), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA—1_T19 (SEQ ID NO:558) is shown in bold; this coding portion starts at position 434 and ends at position 685. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R1172_PEA—1_P13 (SEQ ID NO:591) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
778 G -> T Yes
786 G -> C Yes
1456 C -> T Yes

Variant protein R11723_PEA—1_P10 (SEQ ID NO:592) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA—1_T20 (SEQ ID NO:559). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between R11723_PEA—1_P10 (SEQ ID NO:592) and Q96AC2 (SEQ ID NO: 886):

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P10 (SEQ ID NO:592) comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO: 886), which also corresponds to amino acids 1-63 of R11723_PEA—1_P10 (SEQ ID NO:592), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) corresponding to amino acids 64-90 of R11723_PEA—1_P10 (SEQ ID NO:592), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) in R11723_PEA—1_P10 (SEQ ID NO:592).

Comparison report between R11723_PEA—1_P10 (SEQ ID NO:592) and Q8N2G4:

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P10 (SEQ ID NO:592), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1-63 of Q8N2G4, which also corresponds to amino acids 1-63 of R11723_PEA—1_P10 (SEQ ID NO:592), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) corresponding to amino acids 64-90 of R11723_PEA—1_P10 (SEQ ID NO:592), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) in R11723_PEA—1_P10 (SEQ ID NO:592).

Comparison report between R11723_PEA—1_P10 (SEQ ID NO:592) and BAC85273:

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P10 (SEQ ID NO:592) comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG (SEQ ID NO:1025) corresponding to amino acids 1-5 of R11723_PEA—1_P10 (SEQ ID NO:592), second amino acid sequence being at least 90% homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 22-79 of BAC85273, which also corresponds to amino acids 6-63 of R11723_PEA—1_P10 (SEQ ID NO:592), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) corresponding to amino acids 64-90 of R11723_PEA—1_P10 (SEQ ID NO:592), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R11723_PEA—1_P10 (SEQ ID NO:592) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG (SEQ ID NO:1025) of R11723_PEA—1_P10 (SEQ ID NO:592)

3. An isolated polypeptide encoding for a tail of R11723_PEA—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) in R11723_PEA—1_P10 (SEQ ID NO:592).

Comparison report between R11723_PEA—1_P10 (SEQ ID NO:592) and BAC85518:

1. An isolated chimeric polypeptide encoding for R11723_PEA—1_P10 (SEQ ID NO:592), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 24-86 of BAC85518, which also corresponds to amino acids 1-63 of R11723_PEA—1_P10 (SEQ ID NO:592), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) corresponding to amino acids 64-90 of R11723_PEA—1_P10 (SEQ ID NO:592), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1027) in R11723_PEA—1_P10 (SEQ ID NO:592).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R11723_PEA—1_P10 (SEQ ID NO:592) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P10 (SEQ ID NO:592) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
66 V -> F Yes

Variant protein R11723_PEA—1_P10 (SEQ ID NO:592) is encoded by the following transcript(s): R11723_PEA—1_T20 (SEQ ID NO:559), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA—1_T20 (SEQ ID NO:559) is shown in bold; this coding portion starts at position 434 and ends at position 703. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA—1_P10 (SEQ ID NO:592) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
629 G -> T Yes
637 G -> C Yes
1307 C -> T Yes

As noted above, cluster R11723 features 26 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster R11723_PEA—1_node—13 (SEQ ID NO:562) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T19 (SEQ 624 776
ID NO: 558)
R11723_PEA_1_T5 (SEQ ID 624 776
NO: 560)
R11723_PEA_1_T6 (SEQ ID 658 810
NO: 561)

Segment cluster R11723_PEA—1_node—16 (SEQ ID NO:563) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558) and R11723_PEA—1_T20 (SEQ ID NO:559). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment starting Segment ending
Transcript name position position
R11723_PEA_1_T17 (SEQ 624 1367
ID NO: 557)
R11723_PEA_1_T19 (SEQ 777 1520
ID NO: 558)
R11723_PEA_1_T20 (SEQ 628 1371
ID NO: 559)

Segment cluster R11723_PEA—1_node—19 (SEQ ID NO:564) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T5 (SEQ ID 835 1008
NO: 560)
R11723_PEA_1_T6 (SEQ ID 869 1042
NO: 561)

Segment cluster R11723_PEA—1_node—2 (SEQ ID NO:565) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T5 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 1 309
ID NO: 556)
R11723_PEA_1_T17 (SEQ 1 309
ID NO: 557)
R11723_PEA_1_T19 (SEQ 1 309
ID NO: 558)
R11723_PEA_1_T20 (SEQ 1 309
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 1 309
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1 309
NO: 561)

Segment cluster R11723_PEA—1_node—22 (SEQ ID NO:566) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T5 (SEQ ID 1083 1569
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1117 1603
NO: 561)

Segment cluster R11723_PEA—1_node—31 (SEQ ID NO:567) according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556, R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 20 below describes the starting and ending position of this segment on each transcript (it should be noted that these transcripts show alternative polyadenylation).

TABLE 20
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 1060 1295
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1978 2213
NO: 560)
R11723_PEA_1_T6 (SEQ ID 2012 2247
NO: 561)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster R11723_PEA—1_node—10 (SEQ ID NO:568) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556) R11723_PEA—1_T17(SEQ ID NO:557), R11723—1_PEA—1_T19(SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 486 529
ID NO: 556)
R11723_PEA_1_T17 (SEQ 486 529
ID NO: 557)
R11723_PEA_1_T19 (SEQ 486 529
ID NO: 558)
R11723_PEA_1_T20 (SEQ 486 529
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 486 529
NO: 560)
R11723_PEA_1_T6 (SEQ ID 520 563
NO: 561)

Segment cluster R11723_PEA—1_node—11 (SEQ ID NO:569) according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556, R11723_PEA—1_T17(SEQ ID NO:557), R11723_PEA—1_T19(SEQ ID NO:558), R11723_PEA—1—T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 530 623
ID NO: 556)
R11723_PEA_1_T17 (SEQ 530 623
ID NO: 557)
R11723_PEA_1_T19 (SEQ 530 623
ID NO: 558)
R11723_PEA_1_T20 (SEQ 530 623
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 530 623
NO: 560)
R11723_PEA_1_T6 (SEQ ID 564 657
NO: 561)

Segment cluster R11723_PEA—1_node—15 (SEQ ID NO:570) according to the present invention can be found in the following transcript(s): R11723_PEA—1_T20 (SEQ ID NO:559). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T20 (SEQ 624 627
ID NO: 559)

Segment cluster R11723_PEA—1_node—18 (SEQ ID NO:571) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 624 681
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 777 834
NO: 560)
R11723_PEA_1_T6 (SEQ ID 811 868
NO: 561)

Segment cluster R11723_PEA—1_node—20 (SEQ ID NO:572) according to the present invention can be found in the following transcript(s): R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T5 (SEQ ID 1009 1019
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1043 1053
NO: 561)

Segment cluster R11723_PEA—1_node—21 (SEQ ID NO:573) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T5 (SEQ ID 1020 1082
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1054 1116
NO: 561)

Segment cluster R11723_PEA—1_node—23 (SEQ ID NO:574) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T5 (SEQ ID 1570 1599
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1604 1633
NO: 561)

Segment cluster R11723_PEA—1_node—24 (SEQ ID NO:575) according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 682 765
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1600 1683
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1634 1717
NO: 561)

Segment cluster R11723_PEA—1_node—25 (SEQ ID NO:576) according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 766 791
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1684 1709
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1718 1743
NO: 561)

Segment cluster R11723_PEA—1_node—26 (SEQ ID NO:577) according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 792 904
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1710 1822
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1744 1856
NO: 561)

Segment cluster R11723_PEA—1_node—27 (SEQ ID NO:578) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 905 986
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1823 1904
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1857 1938
NO: 561)

Segment cluster R11723_PEA—1_node—28 (SEQ ID NO:579) according to the present invention can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6(SEQ ID NO:561). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 987 1010
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1905 1928
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1939 1962
NO: 561)

Segment cluster R11723_PEA—1_node—29 (SEQ ID NO:580) according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 1011 1038
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1929 1956
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1963 1990
NO: 561)

Segment cluster R11723_PEA—1_node—3 (SEQ ID NO:581) according to the present invention can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 310 319
ID NO: 556)
R11723_PEA_1_T17 (SEQ 310 319
ID NO: 557)
R11723_PEA_1_T19 (SEQ 310 319
ID NO: 558)
R11723_PEA_1_T20 (SEQ 310 319
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 310 319
NO: 560)
R11723_PEA_1_T6 (SEQ ID 310 319
NO: 561)

Segment cluster R11723_PEA—1_node—30 (SEQ ID NO:582) according to the present invention can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 1039 1059
ID NO: 556)
R11723_PEA_1_T5 (SEQ ID 1957 1977
NO: 560)
R11723_PEA_1_T6 (SEQ ID 1991 2011
NO: 561)

Segment cluster R11723_PEA—1_node—4 (SEQ ID NO:583) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 320 371
ID NO: 556)
R11723_PEA_1_T17 (SEQ 320 371
ID NO: 557)
R11723_PEA_1_T19 (SEQ 320 371
ID NO: 558)
R11723_PEA_1_T20 (SEQ 320 371
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 320 371
NO: 560)
R11723_PEA_1_T6 (SEQ ID 320 371
NO: 561)

Segment cluster R11723_PEA—1_node—5 (SEQ ID NO:584) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 372 414
ID NO: 556)
R11723_PEA_1_T17 (SEQ 372 414
ID NO: 557)
R11723_PEA_1_T19 (SEQ 372 414
ID NO: 558)
R11723_PEA_1_T20 (SEQ 372 414
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 372 414
NO: 560)
R11723_PEA_1_T6 (SEQ ID 372 414
NO: 561)

Segment cluster R11723_PEA—1_node—6 (SEQ ID NO:585) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 415 446
ID NO: 556)
R11723_PEA_1_T17 (SEQ 415 446
ID NO: 557)
R11723_PEA_1_T19 (SEQ 415 446
ID NO: 558)
R11723_PEA_1_T20 (SEQ 415 446
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 415 446
NO: 560)
R11723_PEA_1_T6 (SEQ ID 415 446
NO: 561)

Segment cluster R11723_PEA—1_node—7 (SEQ ID NO:586) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T15 (SEQ ID NO:556), R11723_PEA—1_T17 (SEQ ID NO:557), R11723_PEA—1_T19 (SEQ ID NO:558), R11723_PEA—1_T20 (SEQ ID NO:559), R11723_PEA—1_T5 (SEQ ID NO:560) and R11723_PEA—1_T6 (SEQ ID NO:561). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T15 (SEQ 447 485
ID NO: 556)
R11723_PEA_1_T17 (SEQ 447 485
ID NO: 557)
R11723_PEA_1_T19 (SEQ 447 485
ID NO: 558)
R11723_PEA_1_T20 (SEQ 447 485
ID NO: 559)
R11723_PEA_1_T5 (SEQ ID 447 485
NO: 560)
R11723_PEA_1_T6 (SEQ ID 447 485
NO: 561)

Segment cluster R11723_PEA—1_node—8 (SEQ ID NO:587) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA—1_T6 (SEQ ID NO:561). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
R11723_PEA_1_T6 (SEQ ID 486 519
NO: 561)

Variant protein alignment to the previously known protein:

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8IXM0

Sequence documentation:

Alignment of: R11723_PEA—1_P6 (SEQ ID NO:589)×Q8IXM0.

Alignment segment 1/1:

Quality: 1128.00
Escore: 0
Matching length: 112 Total length: 112
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
111 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 160
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 50
         ·         ·         ·         ·         ·
161 GEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRE 210
||||||||||||||||||||||||||||||||||||||||||||||||||
51 GEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRE 100
         ·
211 RQRKEKHSMRTQ 222
||||||||||||
101 RQRKEKHSMRTQ 112

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q96AC2 (SEQ ID NO: 886)

Sequence documentation:

Alignment of: R11723_PEA—1_P6 (SEQ ID NO:589)×Q96AC2 (SEQ ID NO: 886).

Alignment segment 1/1:

Quality: 835.00
Escore: 0
Matching length: 83 Total length: 83
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·         ·         ·
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83
|||||||||||||||||||||||||||||||||
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA—1_P6 (SEQ ID NO:589)×Q8N2G4.

Alignment segment 1/1:

Quality: 835.00
Escore: 0
Matching length: 83 Total length: 83
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGTAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·         ·         ·
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83
|||||||||||||||||||||||||||||||||
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:BAC85518

Sequence documentation:

Alignment of: R11723_PEA—1_P6 (SEQ ID NO:589)×BAC85518.

Alignment segment 1/1:

Quality: 835.00
Escore: 0
Matching length: 83 Total length: 83
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73
         ·         ·         ·
51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83
|||||||||||||||||||||||||||||||||
74 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 106

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:Q96AC2 (SEQ ID NO: 886)

Sequence documentation:

Alignment of: R11723_PEA—1_P7 (SEQ ID NO:590)×Q96AC2 (SEQ ID NO: 886).

Alignment segment 1/1:

Quality: 654.00
Escore: 0
Matching length: 64 Total length: 64
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·
51 QDMCQKEVMEQSAG 64
||||||||||||||
51 QDMCQKEVMEQSAG 64

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA—1_P7 (SEQ ID NO:590)×Q8N2G4.

Alignment segment 1/1:

Quality: 654.00
Escore: 0
Matching length: 64 Total length: 64
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·
51 QDMCQKEVMEQSAG 64
||||||||||||||
51 QDMCQKEVMEQSAG 64

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:BAC85273

Sequence documentation:

Alignment of: R11723_PEA—1_P7 (SEQ ID NO:590)×BAC85273.

Alignment segment 1/1:

Quality: 600.00
Escore: 0
Matching length: 59 Total length: 59
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55
||||||||||||||||||||||||||||||||||||||||||||||||||
22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71
56 KEVMEQSAG 64
|||||||||
72 KEVMEQSAG 80

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:BAC85518

Sequence documentation:

Alignment of: R11723_PEA—1_P7 (SEQ ID NO:590)×BAC85518.

Alignment segment 1/1:

Quality: 654.00
Escore: 0
Matching length: 64 Total length: 64
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73
         ·
51 QDMCQKEVMEQSAG 64
||||||||||||||
74 QDMCQKEVMEQSAG 87

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q96AC2 (SEQ ID NO: 886)

Sequence documentation:

Alignment of: R11723_PEA—1_P10 (SEQ ID NO:592)×Q96AC2 (SEQ ID NO: 886).

Alignment segment 1/1:

Quality: 645.00
Escore: 0
Matching length: 63 Total length: 63
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·
51 QDMCQKEVMEQSA 63
|||||||||||||
51 QDMCQKEVMEQSA 63

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA—1_P10 (SEQ ID NO:592)×Q8N2G4.

Alignment segment 1/1:

Quality: 645.00
Escore: 0
Matching length: 63 Total length: 63
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·
51 QDMCQKEVMEQSA 63
|||||||||||||
51 QDMCQKEVMEQSA 63

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:BAC85273

Sequence documentation:

Alignment of: R11723_PEA—1_P10 (SEQ ID NO:592)×BAC85273.

Alignment segment 1/1:

Quality: 591.00
Escore: 0
Matching length: 58 Total length: 58
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         .         .         .         .         .
6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55
||||||||||||||||||||||||||||||||||||||||||||||||||
22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71
56 KEVMEQSA 63
||||||||
72 KEVMEQSA 79

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:BAC85518.

Alignment documentation:

Alignment of: R11723_PEA—1_P10 (SEQ ID NO:592)×BAC85518.

Alignment segment 1/1:

Quality: 645.00
Escore: 0
Matching length: 63 Total length: 63
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73
         ·
51 QDMCQKEVMEQSA 63
|||||||||||||
74 QDMCQKEVMEQSA 86

Alignment of: R11723_PEA—1—P13 (SEQ ID NO:591)×Q96AC2 (SEQ ID NO: 886).

Alignment segment 1/1:

Quality: 645.00
Escore: 0
Matching length: 63 Total length: 63
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50
         ·
51 QDMCQKEVMEQSA 63
|||||||||||||
51 QDMCQKEVMEQSA 63

Expression of R11723 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name R11723 Seg13 (SEQ ID NO:891) in Normal and Cancerous Breast Tissues

Expression of transcripts detectable by or according to seg13, R11723 seg13 amplicon(s) (SEQ ID NO:891) and R11723 seg13F (SEQ ID NO:889) and R11723 seg13R (SEQ ID NO:890) primers was measured by real time PCR. It should be noted that the variants of this cluster are variants of the hypothetical protein PSEC0181 (referred to herein as “PSEC”). In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, “Tissue samples in testing panel” above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 39 is a histogram showing over expression of the above-indicated transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 39, the expression of transcripts detectable by the above amplicon(s) in cancer samples was higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 5 out of 28 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R11723 seg13F forward primer (SEQ ID NO:889); and R11723 seg13R reverse primer (SEQ ID NO:890).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R11723 seg13 (SEQ ID NO:891).

R11723seg13F-
ACACTAAAAGAACAAACACCTTGCTC (SEQ ID NO:889)
R11723seg13R-
TCCTCAGAAGGCACATGAAAGA (SEQ ID NO:890)
R11723seg13 amplicon:
ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAGCAGTTG (SEQ ID NO:891)
ACCACTTAGTTCTCAAGAAGCAACTATCTCTTTCATGTGCCTTCTGAGGA

Expression of R11723 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name R11723Seg13 (SEQ ID NO:891) in Different Normal Tissues

Expression of R11723 transcripts detectable by or according to R11723seg13 amplicon (SEQ ID NO:891) and R11723seg13F (SEQ ID NO:889) R11723seg13R (SEQ ID NO:890) was measured by real time PCR. In parallel the expression of four housekeeping genes RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945 ) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20 Table 2 “Tissue samples in normal panel” above), to obtain a value of relative expression of each sample relative to median of the ovary samples. Primers and amplicon are as above.

The results are presented in FIG. 40, demonstrating the expression of R11723 transcripts which are detectable by amplicon as depicted in sequence name R11723seg13 (SEQ ID NO:891) in different normal tissues.

Expression of R11723 Transcripts, Which are Detectable by Amplicon as Depicted in Sequence Name R11723 Junc11-18 (SEQ ID NO:894) in Normal and Cancerous Breast Tissues

Expression of transcripts detectable by or according to junc11-18, R11723 junc 11-18 amplicon(s) (SEQ ID NO:894) and R11723 junc11-18F (SEQ ID NO:892) and R11723 junc11-18R (SEQ ID NO:893) primers was measured by real time PCR (this junction and hence the amplicon are found in the previous known protein, also termed the “wild type” or WT protein, for which the sequence is given herein; the protein is also called “PSEC”). Use of the known protein (WT protein) for detection of breast cancer, alone or in combination with one or more variants of this cluster and/or of any other cluster and/or of any known marker, also comprises an embodiment of the present invention. In parallel the expression of four housekeeping genes PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925 ), and G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 41A is a histogram showing over expression of the above-indicated transcripts in cancerous breast samples relative to the normal samples.

As is evident from FIG. 41A, the expression of transcripts detectable by the above amplicon in a few cancer samples was higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67, Table 5: “Tissue samples in breast cancer testing panel”). Notably an over-expression of at least 5 fold was found in 5 out of 28 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R11723 junc11-18F forward primer (SEQ ID NO:892); and R11723 junc11-18R reverse primer (SEQ ID NO:893).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R11723 junc11-18 (SEQ ID NO:894).

R11723junc11-18F-
AGTGATGGAGCAAAGTGCCG (SEQ ID NO:892)
R11723 junc11-18R-
CAGCAGCTGATGCAAACTGAG (SEQ ID NO:893)
R11723 junc11-18-
AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCATCAGCGG (SEQ ID NO:894)
CCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCAGGGAAACTGAACT
CAGTTTGCATCAGCTGCTG

Expression of R11723 Transcripts, Which were Detected by Amplicon as Depicted in the Sequence Name R11723 junc11-18 (SEQ ID NO:894) in Different Normal Tissues

Expression of R11723 transcripts detectable by or according to R11723seg13 amplicon (SEQ ID NO:894) and R11723 junc11-18F (SEQ ID NO:892) R11723junc11-18R (SEQ ID NO:893) was measured by real time PCR (as described above, this junction and hence the amplicon are found in the previous known protein, also termed the “wild type” or WT protein, for which the sequence is given herein; the protein is also called “PSEC”). In parallel the expression of four housekeeping genes RPL19 (GenBank Accession No. NM—000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM—003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon—Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2: Tissue samples in normal panel, above), to obtain a value of relative expression of each sample relative to median of the ovary samples. FIG. 41B shows the level of expression of this transcript. Primers and amplicon are as for the example above.

The variant transcript expression pattern for this cluster is similar to the wild type transcript expression. However, in some cases (e.g. ovary cancer) over expression of the variant seems to be higher (for example, with regard to R11723_PEA—1—T5 (SEQ ID NO:560)).

Description for Cluster T46984

Cluster T46984 features 21 transcript(s) and 49 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
T46984_PEA_1_T2 593
T46984_PEA_1_T3 594
T46984_PEA_1_T12 595
T46984_PEA_1_T13 596
T46984_PEA_1_T14 597
T46984_PEA_1_T15 598
T46984_PEA_1_T19 599
T46984_PEA_1_T23 600
T46984_PEA_1_T27 601
T46984_PEA_1_T32 602
T46984_PEA_1_T34 603
T46984_PEA_1_T35 604
T46984_PEA_1_T40 605
T46984_PEA_1_T42 606
T46984_PEA_1_T43 607
T46984_PEA_1_T46 608
T46984_PEA_1_T47 609
T46984_PEA_1_T48 610
T46984_PEA_1_T51 611
T46984_PEA_1_T52 612
T46984_PEA_1_T54 613

TABLE 2
Segments of interest
Segment Name Sequence ID No.
T46984_PEA_1_node_2 614
T46984_PEA_1_node_4 615
T46984_PEA_1_node_6 616
T46984_PEA_1_node_12 617
T46984_PEA_1_node_14 618
T46984_PEA_1_node_25 619
T46984_PEA_1_node_29 620
T46984_PEA_1_node_34 621
T46984_PEA_1_node_46 622
T46984_PEA_1_node_47 623
T46984_PEA_1_node_52 624
T46984_PEA_1_node_65 625
T46984_PEA_1_node_69 626
T46984_PEA_1_node_75 627
T46984_PEA_1_node_86 628
T46984_PEA_1_node_9 629
T46984_PEA_1_node_13 630
T46984_PEA_1_node_19 631
T46984_PEA_1_node_21 632
T46984_PEA_1_node_22 633
T46984_PEA_1_node_26 634
T46984_PEA_1_node_28 635
T46984_PEA_1_node_31 636
T46984_PEA_1_node_32 637
T46984_PEA_1_node_38 638
T46984_PEA_1_node_39 639
T46984_PEA_1_node_40 640
T46984_PEA_1_node_42 641
T46984_PEA_1_node_43 642
T46984_PEA_1_node_48 643
T46984_PEA_1_node_49 644
T46984_PEA_1_node_50 645
T46984_PEA_1_node_51 646
T46984_PEA_1_node_53 647
T46984_PEA_1_node_54 648
T46984_PEA_1_node_55 649
T46984_PEA_1_node_57 650
T46984_PEA_1_node_60 651
T46984_PEA_1_node_62 652
T46984_PEA_1_node_66 653
T46984_PEA_1_node_67 654
T46984_PEA_1_node_70 655
T46984_PEA_1_node_71 656
T46984_PEA_1_node_72 657
T46984_PEA_1_node_73 658
T46984_PEA_1_node_74 659
T46984_PEA_1_node_83 660
T46984_PEA_1_node_84 661
T46984_PEA_1_node_85 662

TABLE 3
Proteins of interest
Sequence ID
Protein Name No. Corresponding Transcript(s)
T46984_PEA_1_P2 664 T46984_PEA_1_T2 (SEQ ID
NO: 593);
T46984_PEA_1_T12 (SEQ
ID NO: 595);
T46984_PEA_1_T23 (SEQ
ID NO: 600)
T46984_PEA_1_P3 665 T46984_PEA_1_T3 (SEQ ID
NO: 594);
T46984_PEA_1_T19 (SEQ
ID NO: 599)
T46984_PEA_1_P10 666 T46984_PEA_1_T13 (SEQ
ID NO: 596)
T46984_PEA_1_P11 667 T46984_PEA_1_T14 (SEQ
ID NO: 597)
T46984_PEA_1_P12 668 T46984_PEA_1_T15 (SEQ
ID NO: 598)
T46984_PEA_1_P21 669 T46984_PEA_1_T27 (SEQ
ID NO: 601)
T46984_PEA_1_P27 670 T46984_PEA_1_T34 (SEQ
ID NO: 603)
T46984_PEA_1_P32 671 T46984_PEA_1_T40 (SEQ
ID NO: 605)
T46984_PEA_1_P34 672 T46984_PEA_1_T42 (SEQ
ID NO: 606)
T46984_PEA_1_P35 673 T46984_PEA_1_T43 (SEQ
ID NO: 607)
T46984_PEA_1_P38 674 T46984_PEA_1_T47 (SEQ
ID NO: 609)
T46984_PEA_1_P39 675 T46984_PEA_1_T48 (SEQ
ID NO: 610)
T46984_PEA_1_P45 676 T46984_PEA_1_T32 (SEQ
ID NO: 602)
T46984_PEA_1_P46 677 T46984_PEA_1_T35 (SEQ
ID NO: 604)

These sequences are variants of the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SwissProt accession identifier RIB2_HUMAN; known also according to the synonyms EC 2.4.1.119; Ribophorin II; RPN-II; RIBIIR), SEQ ID NO: 663, referred to herein as the previously known protein.

Protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663) is known or believed to have the following function(s): Essential subunit of N-oligosaccharyl transferase enzyme which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. The sequence for protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663) is given at the end of the application, as “Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
197 V -> L
201 F -> C
260 A -> S
423 V -> M

Protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663) localization is believed to be Type I membrane protein. Endoplasmic reticulum.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein modification, which are annotation(s) related to Biological Process; oligosaccharyl transferase; dolichyl-diphosphooligosaccharide-protein glycosyltransferase; transferase, which are annotation(s) related to Molecular Function; and oligosaccharyl transferase complex; integral membrane protein, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster T46984 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 42 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 42 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

TABLE 5
Normal tissue distribution
Name of Tissue Number
adrenal 240
bladder 287
bone 592
brain 145
colon 157
epithelial 144
general 163
head and neck 50
kidney 139
liver 156
lung 155
lymph nodes 194
breast 105
bone marrow 62
muscle 62
ovary 0
pancreas 72
prostate 201
skin 91
stomach 219
T cells 0
Thyroid 0
uterus 200

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
adrenal 6.3e−01 5.4e−01 6.2e−01 0.8 2.5e−01 1.0
bladder 5.4e−01 5.9e−01 3.0e−01 1.0 6.5e−01 0.7
bone 3.9e−01 3.7e−01 9.8e−01 0.4 9.9e−01 0.4
brain 3.3e−01 2.9e−01 1.4e−01 1.2 2.0e−01 1.0
colon 8.6e−02 5.9e−02 2.6e−01 1.3 2.1e−03 1.4
epithelial 5.3e−05 6.2e−07 2.8e−08 1.9 3.4e−21 2.4
general 1.0e−04 7.3e−08 9.3e−12 1.7 8.0e−33 2.0
head and neck 4.5e−01 5.4e−01 1 0.8 7.5e−01 0.9
kidney 6.6e−01 6.5e−01 3.2e−01 1.2 5.3e−02 1.5
liver 5.5e−01 5.6e−01 6.5e−01 1.0 1.2e−01 1.4
lung 3.0e−01 1.7e−01 1.5e−01 1.4 6.0e−02 1.4
lymph nodes 2.9e−01 5.5e−01 2.9e−01 0.8 4.3e−01 1.0
breast 2.4e−02 5.8e−03 3.7e−02 2.2 1.7e−04 2.7
bone marrow 7.1e−01 7.5e−01 1 0.3 1.2e−02 1.8
muscle 5.0e−01 3.7e−01 4.7e−01 1.5 2.1e−08 1.3
ovary 1.6e−02 7.0e−03 1.5e−02 6.1 4.8e−06 7.1
pancreas 1.4e−01 5.4e−02 2.2e−05 2.9 2.4e−07 3.9
prostate 3.4e−01 1.9e−01 2.2e−01 1.2 1.4e−01 1.3
skin 3.7e−01 1.5e−01 4.2e−02 2.4 1.1e−04 1.9
stomach 6.1e−01 1.4e−01 7.3e−01 0.4 6.1e−02 1.6
T cells 1 6.7e−01 1 1.0 5.2e−01 1.8
Thyroid 4.8e−02 4.8e−02 2.0e−01 3.4 2.0e−01 3.4
uterus 2.3e−01 1.3e−01 2.2e−02 1.5 5.0e−02 1.4

As noted above, cluster T46984 features 21 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663). A description of each variant protein according to the present invention is now provided.

Variant protein T46984_PEA—1_P2 (SEQ ID NO:664) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T2 (SEQ ID NO:593). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P2 (SEQ ID NO:664) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P2 (SEQ ID NO:664), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1-498 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-498 of T46984_PEA—1_P2 (SEQ ID NO:664), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VCA corresponding to amino acids 499-501 of T46984_PEA—1_P2 (SEQ ID NO:664), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

The glycosylation sites of variant protein T46984_PEA—1_P2 (SEQ ID NO:664), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 7 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 7
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
106 yes 106

Variant protein T46984_PEA—1_P2 (SEQ ID NO:664) is encoded by the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T2 (SEQ ID NO:593) is shown in bold; this coding portion starts at position 316 and ends at position 1818. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P2 (SEQ ID NO:664) sequence provides support for the deduced sequence of the variant protein according to the present invention).

TABLE 8
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1376 G -> T Yes
1588 A -> C No
1618 T -> No
1618 T -> C No
1660 T -> No
1693 A -> C No
1693 A -> T No
2099 G -> A Yes
2124 C -> G Yes
2124 C -> T Yes
2133 A -> G Yes
2501 C -> T Yes
2617 G -> T Yes
2683 C -> T Yes
2741 G -> A Yes
2940 T -> No
3024 G -> A Yes
3158 C -> No
3158 C -> A No
3165 C -> No
3169 G -> No
3354 C -> A No
3374 T -> C Yes
3468 C -> T No
3501 A -> C No
3513 A -> T No
3528 G -> A Yes
3534 -> A No
3543 A -> G No
3568 T -> G No
3582 T -> A No
3582 T -> G No
3682 -> C No
3691 T -> No
3750 A -> C No

Variant protein T46984_PEA—1_P3 (SEQ ID NO:665) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T3 (SEQ ID NO:594). An alignment is given to the known protein (Dolichyl-diphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P3 (SEQ ID NO:665) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P3 (SEQ ID NO:665), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQ corresponding to amino acids 1-433 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-433 of T46984_PEA—1_P3 (SEQ ID NO:665), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ICHIWKLIFLP (SEQ ID NO:947) corresponding to amino acids 434-444 of T46984_PEA—1_P3 (SEQ ID NO:665), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1_P3 (SEQ ID NO:665), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ICHIWKLIFLP (SEQ ID NO:947) in T46984_PEA—1_P3 (SEQ ID NO:665).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P3 (SEQ ID NO:665) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P3 (SEQ ID NO:665) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> No
291 Q -> P No
302 Q -> R No
302 Q -> L No
326 T -> P No
330 D -> N No
354 G -> V Yes
425 T -> P No

The glycosylation sites of variant protein T46984_PEA—1_P3 (SEQ ID NO:665), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 10 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 10
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
106 yes 106

Variant protein T46984_PEA—1_P3 (SEQ ID NO:665) is encoded by the following transcript(s): T46984_PEA—1_T3 (SEQ ID NO:594), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T3 (SEQ ID NO:594) is shown in bold; this coding portion starts at position 316 and ends at position 1647. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P3 (SEQ ID NO:665) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1376 G -> T Yes
1588 A -> C No
1784 C -> T Yes
1959 G -> A Yes
2112 G -> A Yes
2137 C -> G Yes
2246 T -> No
2246 T -> C No
2288 T -> No
2321 A -> C No
2321 A -> T No
2552 C -> No
2552 C -> A No
2559 C -> No
2563 G -> No
2748 C -> A No
2768 T -> C Yes
2862 C -> T No
2895 A -> C No
2907 A -> T No
2922 G -> A Yes
2928 -> A No
2937 A -> G No
2962 T -> G No
2976 T -> A No
2976 T -> G No
3076 -> C No
3085 T -> No
3144 A -> C No

Variant protein T46984_PEA—1_P10 (SEQ ID NO:666) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T13 (SEQ ID NO:596). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P10 (SEQ ID NO:666) and RIB2_HUMAN SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P10 (SEQ ID NO:666), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1-498 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-498 of T46984_PEA—1_P10 (SEQ ID NO:666), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LMDQK (SEQ ID NO:948) corresponding to amino acids 499-503 of T46984_PEA—1_P10 (SEQ ID NO:666), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1—P10 (SEQ ID NO:666), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LMDQK (SEQ ID NO:948) in T46984_PEA—1_P10 (SEQ ID NO:666)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P10 (SEQ ID NO:666) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P10 (SEQ ID NO:666) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> No
291 Q -> P No
302 Q -> R No
302 Q -> L No
326 T -> P No
330 D -> N No
354 G -> V Yes
425 T -> P No
435 F -> No
435 F -> L No
449 F -> No
460 K -> * No
460 K -> Q No

The glycosylation sites of variant protein T46984_PEA—1_P10 (SEQ ID NO:666), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 13 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 13
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 106

Variant protein T46984_PEA—1_P10 (SEQ ID NO:666) is encoded by the following transcript(s): T46984_PEA—1_T13 (SEQ ID NO:596), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T13 (SEQ ID NO:596) is shown in bold; this coding portion starts at position 316 and ends at position 1824. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P10 (SEQ ID NO:666) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1376 G -> T Yes
1588 A -> C No
1618 T -> No
1618 T -> C No
1660 T -> No
1693 A -> C No
1693 A -> T No
1845 T -> No
1983 C -> No
1983 C -> A No
1990 C -> No
1994 G -> No
2179 C -> A No
2199 T -> C Yes
2293 C -> T No
2326 A -> C No
2338 A -> T No
2353 G -> A Yes
2359 -> A No
2368 A -> G No
2393 T -> G No
2407 T -> A No
2407 T -> G No
2507 -> C No
2516 T -> No
2575 A -> C No

Variant protein T46984_PEA—1_P11 (SEQ ID NO:667) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T14 (SEQ ID NO:597). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P11 (SEQ ID NO:667) and RIB2_HUMAN SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P11 (SEQ ID NO:667), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEK RPPTVVSNTFTALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWT QLNMFQTLKYLAILGSVTFLAGNRMLAQQAVKR corresponding to amino acids 1-628 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-628 of T46984_PEA—1_P11 (SEQ ID NO:667).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

Variant protein T46984_PEA—1_P11 (SEQ ID NO:667) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P11 (SEQ ID NO:667) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> P No
291 Q -> No
302 Q -> L No
302 Q -> R No
326 T -> P No
330 D -> N No
354 G -> V Yes
425 T -> P No
435 F -> No
435 F -> L No
449 F -> No
460 K -> Q No
460 K -> * No
537 P -> T No
537 P -> No
539 T -> No
540 V -> No
602 T -> N No

The glycosylation sites of variant protein T46984_PEA—1_P11 (SEQ ID NO:667), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 16 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 16
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 106

Variant protein T46984_PEA—1_P11 (SEQ ID NO:667) is encoded by the following transcript(s): T46984_PEA—1_T14 (SEQ ID NO:597), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T14 (SEQ ID NO:597) is shown in bold; this coding portion starts at position 316 and ends at position 2199. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P11 (SEQ ID NO:667) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1376 G -> T Yes
1588 A -> C No
1618 T -> No
1618 T -> C No
1660 T -> No
1693 A -> C No
1693 A -> T No
1924 C -> No
1924 C -> A No
1931 C -> No
1935 G -> No
2120 C -> A No
2140 T -> C Yes
2449 A -> Yes
2537 C -> T Yes
2614 C -> T Yes
2699 C -> T Yes
2857 G -> A Yes
2879 A -> G Yes
3078 A -> G Yes
3354 G -> A Yes

Variant protein T46984_PEA—1_P12 (SEQ ID NO:668) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T15 (SEQ ID NO:598). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P12 (SEQ ID NO:668) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P12 (SEQ ID NO:668), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMN corresponding to amino acids 1-338 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-338 of T46984_PEA—1_P12 (SEQ ID NO:668), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SQDLH (SEQ ID NO:949) corresponding to amino acids 339-343 of T46984_PEA—1_P12 (SEQ ID NO:668), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1_P12 (SEQ ID NO:668), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SQDLH (SEQ ID NO:949) in T46984_PEA—1_P12 (SEQ ID NO:668).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P12 (SEQ ID NO:668) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 18, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P12 (SEQ ID NO:668) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> No
291 Q -> P No
302 Q -> L No
302 Q -> R No
326 T -> P No
330 D -> N No

The glycosylation sites of variant protein T46984_PEA—1_P12 (SEQ ID NO:668), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 19 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 19
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 106

Variant protein T46984_PEA—1_P12 (SEQ ID NO:668) is encoded by the following transcript(s): T46984_PEA—1_T15 (SEQ ID NO:598), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T15 (SEQ ID NO:598) is shown in bold; this coding portion starts at position 316 and ends at position 1344. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P12 (SEQ ID NO:668) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1505 A -> C No
1535 T -> No
1535 T -> C No
1577 T -> No
1610 A -> C No
1610 A -> T No
1841 C -> No
1841 C -> A No
1848 C -> No
1852 G -> No
2037 C -> A No
2057 T -> C Yes
2151 C -> T No
2184 A -> C No
2196 A -> T No
2211 G -> A Yes
2217 -> A No
2226 A -> G No
2251 T -> G No
2265 T -> A No
2265 T -> G No
2365 -> C No
2374 T -> No
2433 A -> C No

Variant protein T46984_PEA—1_P21 (SEQ ID NO:669) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T27 (SEQ ID NO:601). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P21 (SEQ ID NO:669) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P21 (SEQ ID NO:669), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence M corresponding to amino acids 1-1 of T46984_PEA—1_P21 (SEQ ID NO:669), and a second amino acid sequence being at least 90% homologous to KACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSSVTQIYHAV AALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVA RLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFES LSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPLTQATVKL EHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIANTVEL RVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQLVDVNT GAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDSASGTYTLYLII GDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEKRPPTVVSNTF TALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWTQLNMFQTLKY LAILGSVTFLAGNRMLAQQAVKRTAH corresponding to amino acids 70-631 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 2-563 of T46984_PEA—1_P21 (SEQ ID NO:669), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein T46984_PEA—1_P21 (SEQ ID NO:669) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 21, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P21 (SEQ ID NO:669) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
31 G -> R Yes
67 F -> No
69 L -> No
122 R -> No
177 N -> No
177 N -> D No
183 E -> D No
186 S -> N Yes
223 Q -> P No
223 Q -> No
234 Q -> L No
234 Q -> R No
258 T -> P No
262 D -> N No
286 G -> V Yes
357 T -> P No
367 F -> L No
367 F -> No
381 F -> No
392 K -> * No
392 K -> Q No
469 P -> No
469 P -> T No
471 T -> No
472 V -> No
534 T -> N No

The glycosylation sites of variant protein T46984_PEA—1_P21 (SEQ ID NO:669), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 22 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 22
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 38

Variant protein T46984_PEA—1_P21 (SEQ ID NO:669) is encoded by the following transcript(s): T46984_PEA—1_T27 (SEQ ID NO:601), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T27 (SEQ ID NO:601) is shown in bold; this coding portion starts at position 338 and ends at position 2026. The transcript also has the following SNPs as listed in Table 23 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P21 (SEQ ID NO:669) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
68 C -> T Yes
194 A -> G Yes
428 G -> A Yes
536 T -> No
542 C -> No
662 C -> T Yes
675 -> G No
703 C -> No
715 -> G No
820 G -> A No
866 A -> No
866 A -> G No
886 A -> C No
894 G -> A Yes
1005 A -> No
1005 A -> C No
1038 A -> G No
1038 A -> T No
1072 T -> G No
1109 A -> C No
1111 C -> G No
1121 G -> A No
1194 G -> T Yes
1406 A -> C No
1436 T -> No
1436 T -> C No
1478 T -> No
1511 A -> C No
1511 A -> T No
1742 C -> No
1742 C -> A No
1749 C -> No
1753 G -> No
1938 C -> A No
1958 T -> C Yes
2052 C -> T No
2085 A -> C No
2097 A -> T No
2112 G -> A Yes
2118 -> A No
2127 A -> G No
2152 T -> G No
2166 T -> A No
2166 T -> G No
2266 -> C No
2275 T -> No
2334 A -> C No

Variant protein T46984_PEA—1_P27 (SEQ ID NO:670) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T34 (SEQ ID NO:603). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P27 (SEQ ID NO:670) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P27 (SEQ ID NO:670) comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFA corresponding to amino acids 1-415 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-415 of T46984_PEA—1_P27 (SEQ ID NO:670), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP (SEQ ID NO:950) corresponding to amino acids 416-459 of T46984_PEA—1_P27 (SEQ ID NO:670), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1_P27 (SEQ ID NO:670), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP (SEQ ID NO:950) in T46984_PEA—1_P27 (SEQ ID NO:670).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P27 (SEQ ID NO:670) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 24, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P27 (SEQ ID NO:670) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> No
291 Q -> P No
302 Q -> R No
302 Q -> L No
326 T -> P No
330 D -> N No
354 G -> V Yes
459 P -> T No

The glycosylation sites of variant protein T46984_PEA—1_P27 (SEQ ID NO:670), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 25 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 25
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 106

Variant protein T46984_PEA—1_P27 (SEQ ID NO:670) is encoded by the following transcript(s): T46984_PEA—1_T34 (SEQ ID NO:603), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T34 (SEQ ID NO:603) is shown in bold; this coding portion starts at position 316 and ends at position 1692. The transcript also has the following SNPs as listed in Table 26 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P27 (SEQ ID NO:670) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1376 G -> T Yes
1690 C -> A No
1710 T -> C Yes
1804 C -> T No
1837 A -> C No
1849 A -> T No
1864 G -> A Yes
1870 -> A No
1879 A -> G No
1904 T -> G No
1918 T -> A No
1918 T -> G No
2018 -> C No
2027 T -> No
2086 A -> C No

Variant protein T46984_PEA—1_P32 (SEQ ID NO:671) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T40 (SEQ ID NO:605). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P32 (SEQ ID NO:671) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P32 (SEQ ID NO:671), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVE corresponding to amino acids 1-364 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-364 of T46984_PEA—1_P32 (SEQ ID NO:671), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT (SEQ ID NO:95 1) corresponding to amino acids 365-397 of T46984_PEA—1_P32 (SEQ ID NO:671), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1_P32 (SEQ ID NO:671), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT (SEQ ID NO:951) in T46984_PEA—1_P32 (SEQ ID NO:671).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P32 (SEQ ID NO:671) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 27, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P32 (SEQ ID NO:671) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> No
291 Q -> P No
302 Q -> R No
302 Q -> L No
326 T -> P No
330 D -> N No
354 G -> V Yes

The glycosylation sites of variant protein T46984_PEA—1_P32 (SEQ ID NO:671), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 28 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 28
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 106

Variant protein T46984_PEA—1_P32 (SEQ ID NO:671) is encoded by the following transcript(s): T46984_PEA—1_T40 (SEQ ID NO:605), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T40 (SEQ ID NO:605) is shown in bold; this coding portion starts at position 316 and ends at position 1506. The transcript also has the following SNPs as listed in Table 29 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P32 (SEQ ID NO:671) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1303 G -> A No
1376 G -> T Yes

Variant protein T46984_PEA—1_P34 (SEQ ID NO:672) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T42 (SEQ ID NO:606). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P34 (SEQ ID NO:672) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P34 (SEQ ID NO:672), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVG corresponding to amino acids 1-329 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-329 of T46984_PEA—1_P34 (SEQ ID NO:672).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P34 (SEQ ID NO:672) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 30, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P34 (SEQ ID NO:672) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 30
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
291 Q -> No
291 Q -> P No
302 Q -> L No
302 Q -> R No
326 T -> P No

The glycosylation sites of variant protein T46984_PEA—1_P34 (SEQ ID NO:672), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 31 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 31
Glycosylation site(s)
Position(s) on known Present in Position in
amino acid sequence variant protein? variant protein?
106 yes 106

Variant protein T46984_PEA—1_P34 (SEQ ID NO:672) is encoded by the following transcript(s): T46984_PEA—1_T42 (SEQ ID NO:606), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T42 (SEQ ID NO:606) is shown in bold; this coding portion starts at position 316 and ends at position 1302. The transcript also has the following SNPs as listed in Table 32 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P34 (SEQ ID NO:672) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 32
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1187 A -> No
1187 A -> C No
1220 A -> G No
1220 A -> T No
1254 T -> G No
1291 A -> C No
1293 C -> G No
1324 T -> C Yes
1489 G -> A Yes

Variant protein T46984_PEA—1_P35 (SEQ ID NO:673) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T43 (SEQ ID NO:607). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P35 (SEQ ID NO:673) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P35 (SEQ ID NO:673), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAI corresponding to amino acids 1-287 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-287 of T46984_PEA—1_P35 (SEQ ID NO:673), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI (SEQ ID NO:952) corresponding to amino acids 288-334 of T46984_PEA—1_P35 (SEQ ID NO:673), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1_P35 (SEQ ID NO:673), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI (SEQ ID NO:952)
in T46984_PEA_1_P35. (SEQ ID NO:673)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P35 (SEQ ID NO:673) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 33, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P35 (SEQ ID NO:673) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 33
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No
190 R -> No
245 N -> No
245 N -> D No
251 E -> D No
254 S -> N Yes
320 T -> P No
324 M -> L No
329 E -> K Yes
334 I -> V No

The glycosylation sites of variant protein T46984_PEA—1_P35 (SEQ ID NO:673), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 34 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 34
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
106 yes 106

Variant protein T46984_PEA—1_P35 (SEQ ID NO:673) is encoded by the following transcript(s): T46984_PEA—1_T43 (SEQ ID NO:607), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T43 (SEQ ID NO:607) is shown in bold; this coding portion starts at position 316 and ends at position 1317. The transcript also has the following SNPs as listed in Table 35 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P35 (SEQ ID NO:673) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 35
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
844 C -> T Yes
857 -> G No
885 C -> No
897 -> G No
1002 G -> A No
1048 A -> No
1048 A -> G No
1068 A -> C No
1076 G -> A Yes
1240 C -> T No
1273 A -> C No
1285 A -> T No
1300 G -> A Yes
1306 -> A No
1315 A -> G No
1340 T -> G No
1354 T -> A No
1354 T -> G No
1454 -> C No
1463 T -> No
1522 A -> C No

Variant protein T46984_PEA—1_P38 (SEQ ID NO:674) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T47 (SEQ ID NO:609). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P38 (SEQ ID NO:674) and RIB2_HUMAN (SEQ ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P38 (SEQ ID NO:674) comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEAL corresponding to amino acids 1-145 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-145 of T46984_PEA—1_P38 (SEQ ID NO:674), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDPDWCQCLQLHFCS (SEQ ID NO:953) corresponding to amino acids 146-160 of T46984_PEA—1_P38 (SEQ ID NO:674), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T46984_PEA—1_P38 (SEQ ID NO:674), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDPDWCQCLQLHFCS (SEQ ID NO:953) in T46984_PEA—1_P38 (SEQ ID NO:674).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P38 (SEQ ID NO:674) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 36, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P38 (SEQ ID NO:674) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 36
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No

The glycosylation sites of variant protein T46984_PEA—1_P38 (SEQ ID NO:674), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 37 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 37
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
106 yes 106

Variant protein T46984_PEA—1_P38 (SEQ ID NO:674) is encoded by the following transcript(s): T46984_PEA—1_T47 (SEQ ID NO:609), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T47 (SEQ ID NO:609) is shown in bold; this coding portion starts at position 316 and ends at position 795. The transcript also has the following SNPs as listed in Table 38 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984—PEA—1_P38 (SEQ ID NO:674) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 38
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
879 C -> A No
899 T -> C Yes
993 C -> T No
1026 A -> C No
1038 A -> T No
1053 G -> A Yes
1059 -> A No
1068 A -> G No
1093 T -> G No
1107 T -> A No
1107 T -> G No
1207 -> C No
1216 T -> No
1275 A -> C No

Variant protein T46984_PEA—1_P39 (SEQ ID NO:675) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T48 (SEQ ID NO:610). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P39 (SEQ ID NO:675) and RIB2_HUMAN (SEQ ID NO:663):

1.An isolated chimeric polypeptide encoding for T46984_PEA—1_P39 (SEQ ID NO:675), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLA corresponding to amino acids 1-160 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-160 of T46984_PEA—1_P39 (SEQ ID NO:675).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P39 (SEQ ID NO:675) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 39, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P39 (SEQ ID NO:675) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 39
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes
135 F -> No
137 L -> No

The glycosylation sites of variant protein T46984_PEA—1_P39 (SEQ ID NO:675), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 40 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 40
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
106 yes 106

Variant protein T46984_PEA—1_P39 (SEQ ID NO:675) is encoded by the following transcript(s): T46984_PEA—1_T48 (SEQ ID NO:610), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T48 (SEQ ID NO:610) is shown in bold; this coding portion starts at position 316 and ends at position 795. The transcript also has the following SNPs as listed in Table 41 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P39 (SEQ ID NO:675) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 41
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
718 T -> No
724 C -> No
848 G -> T Yes
879 C -> G Yes
1008 A -> G Yes
1397 A -> G Yes

Variant protein T46984_PEA—1_P45 (SEQ ID NO:676) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T32 (SEQ ID NO:602). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P45 (SEQ ID NO:676) and RIB2_HUMAN (SEQ. ID NO:663):

1.An isolated chimeric polypeptide encoding for T46984_PEA—1_P45 (SEQ ID NO:676), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCE corresponding to amino acids 1-101 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-101 of T46984_PEA—1_P45 (SEQ ID NO:676), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) corresponding to amino acids 102-116 of T46984_PEA—1_P45 (SEQ ID NO:676), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of T46984_PEA—1_P45 (SEQ ID NO:676), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) in T46984_PEA—1_P45 (SEQ ID NO:676).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P45 (SEQ ID NO:676) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 42, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P45 (SEQ ID NO:676) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 42
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 P -> No
25 P -> R Yes
99 G -> R Yes

The glycosylation sites of variant protein T46984_PEA—1_P45 (SEQ ID NO:676), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 43 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 43
Glycosylation site(s)
Position(s) on known Present in
amino acid sequence variant protein?
106 no

Variant protein T46984_PEA—1_P45 (SEQ ID NO:676) is encoded by the following transcript(s): T46984_PEA—1_T32 (SEQ ID NO:602), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T32 (SEQ ID NO:602) is shown in bold; this coding portion starts at position 316 and ends at position 663. The transcript also has the following SNPs as listed in Table 44 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P45 (SEQ ID NO:676) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 44
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
610 G -> A Yes
668 C -> T Yes
681 -> G No
709 C -> No
721 -> G No
826 G -> A No
872 A -> No
872 A -> G No
892 A -> C No
900 G -> A Yes
1011 A -> No
1011 A -> C No
1044 A -> G No
1044 A -> T No
1078 T -> G No
1115 A -> C No
1117 C -> G No
1127 G -> A No
1200 G -> T Yes
1412 A -> C No
1442 T -> No
1442 T -> C No
1484 T -> No
1517 A -> C No
1517 A -> T No
1748 C -> No
1748 C -> A No
1755 C -> No
1759 G -> No
1944 C -> A No
1964 T -> C Yes
2058 C -> T No
2091 A -> C No
2103 A -> T No
2118 G -> A Yes
2124 -> A No
2133 A -> G No
2158 T -> G No
2172 T -> A No
2172 T -> G No
2272 -> C No
2281 T -> No
2340 A -> C No

Variant protein T46984_PEA—1_P46 (SEQ ID NO:677) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T46984_PEA—1_T35 (SEQ ID NO:604). An alignment is given to the known protein (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T46984_PEA—1_P46 (SEQ ID NO:677) and RIB2_HUMAN (SEQ. ID NO:663):

1. An isolated chimeric polypeptide encoding for T46984_PEA—1_P46 (SEQ ID NO:677), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAK corresponding to amino acids 1-69 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-69 of T46984_PEA—1_P46 (SEQ ID NO:677), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) corresponding to amino acids 70-84 of T46984_PEA—1_P46 (SEQ ID NO:677), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of T46984_PEA—1_P46 (SEQ ID NO:677), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) in T46984_PEA—1_P46 (SEQ ID NO:677).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein T46984_PEA—1_P46 (SEQ ID NO:677) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 45, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P46 (SEQ ID NO:677) sequence provides support for the deduced sequence of this variant protein according to the present invention)

TABLE 45
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 P -> No
25 P -> R Yes

The glycosylation sites of variant protein T46984_PEA—1_P46 (SEQ ID NO:677), as compared to the known protein Dolichyl-diphosphooligosaccharide—protein glycosyltransferase 63 kDa subunit precursor (SEQ ID NO:663), are described in Table 46 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 46
Glycosylation site(s)
Position(s) on known Present in
amino acid sequence variant protein?
106 no

Variant protein T46984_PEA—1_P46 (SEQ ID NO:677) is encoded by the following transcript(s): T46984_PEA—1_T35 (SEQ ID NO:604), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T46984_PEA—1_T35 (SEQ ID NO:604) is shown in bold; this coding portion starts at position 316 and ends at position 567. The transcript also has the following SNPs as listed in Table 47 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T46984_PEA—1_P46 (SEQ ID NO:677) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 47
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
28 G -> C No
173 G -> C Yes
256 C -> T Yes
274 G -> C Yes
325 C -> No
389 C -> G Yes
572 C -> T Yes
585 -> G No
613 C -> No
625 -> G No
730 G -> A No
776 A -> No
776 A -> G No
796 A -> C No
804 G -> A Yes
915 A -> No
915 A -> C No
948 A -> G No
948 A -> T No
982 T -> G No
1019 A -> C No
1021 C -> G No
1031 G -> A No
1104 G -> T Yes
1316 A -> C No
1346 T -> No
1346 T -> C No
1388 T -> No
1421 A -> C No
1421 A -> T No
1652 C -> No
1652 C -> A No
1659 C -> No
1663 G -> No
1848 C -> A No
1868 T -> C Yes
1962 C -> T No
1995 A -> C No
2007 A -> T No
2022 G -> A Yes
2028 -> A No
2037 A -> G No
2062 T -> G No
2076 T -> A No
2076 T -> G No
2176 -> C No
2185 T -> No
2244 A -> C No

As noted above, cluster T46984 features 49 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T46984_PEA—1_node—2 (SEQ ID NO:614) according to the present invention is supported by 240 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T47 (SEQ ID NO:609) and T46984_PEA—1_T48 (SEQ ID NO:610). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1 328
T46984_PEA_1_T3 (SEQ ID NO: 594) 1 328
T46984_PEA_1_T12 (SEQ ID 1 328
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1 328
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1 328
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1 328
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1 328
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1 328
NO: 600)
T46984_PEA_1_T32 (SEQ ID 1 328
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1 328
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1 328
NO: 604)
T46984_PEA_1_T40 (SEQ ID 1 328
NO: 605)
T46984_PEA_1_T42 (SEQ ID 1 328
NO: 606)
T46984_PEA_1_T43 (SEQ ID 1 328
NO: 607)
T46984_PEA_1_T47 (SEQ ID 1 328
NO: 609)
T46984_PEA_1_T48 (SEQ ID 1 328
NO: 610)

Segment cluster T46984_PEA—1_node—4 (SEQ ID NO:615) according to the present invention is supported by 321 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T47 (SEQ ID NO:609) and T46984_PEA—1_T48 (SEQ ID NO:610). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 329 522
T46984_PEA_1_T3 (SEQ ID NO: 594) 329 522
T46984_PEA_1_T12 (SEQ ID 329 522
NO: 595)
T46984_PEA_1_T13 (SEQ ID 329 522
NO: 596)
T46984_PEA_1_T14 (SEQ ID 329 522
NO: 597)
T46984_PEA_1_T15 (SEQ ID 329 522
NO: 598)
T46984_PEA_1_T19 (SEQ ID 329 522
NO: 599)
T46984_PEA_1_T23 (SEQ ID 329 522
NO: 600)
T46984_PEA_1_T32 (SEQ ID 329 522
NO: 602)
T46984_PEA_1_T34 (SEQ ID 329 522
NO: 603)
T46984_PEA_1_T35 (SEQ ID 329 522
NO: 604)
T46984_PEA_1_T40 (SEQ ID 329 522
NO: 605)
T46984_PEA_1_T42 (SEQ ID 329 522
NO: 606)
T46984_PEA_1_T43 (SEQ ID 329 522
NO: 607)
T46984_PEA_1_T47 (SEQ ID 329 522
NO: 609)
T46984_PEA_1_T48 (SEQ ID 329 522
NO: 610)

Segment cluster T46984_PEA—1_node—6 (SEQ ID NO:616) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T27 (SEQ ID NO:601). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T27 (SEQ ID 1 340
NO: 601)

Segment cluster T46984_PEA—1_node—12 (SEQ ID NO:617) according to the present invention is supported by 262 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T47 (SEQ ID NO:609) and T46984_PEA—1_T48 (SEQ ID NO:610). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 619 751
T46984_PEA_1_T3 (SEQ ID NO: 594) 619 751
T46984_PEA_1_T12 (SEQ ID 619 751
NO: 595)
T46984_PEA_1_T13 (SEQ ID 619 751
NO: 596)
T46984_PEA_1_T14 (SEQ ID 619 751
NO: 597)
T46984_PEA_1_T15 (SEQ ID 619 751
NO: 598)
T46984_PEA_1_T19 (SEQ ID 619 751
NO: 599)
T46984_PEA_1_T23 (SEQ ID 619 751
NO: 600)
T46984_PEA_1_T27 (SEQ ID 437 569
NO: 601)
T46984_PEA_1_T34 (SEQ ID 619 751
NO: 603)
T46984_PEA_1_T40 (SEQ ID 619 751
NO: 605)
T46984_PEA_1_T42 (SEQ ID 619 751
NO: 606)
T46984_PEA_1_T43 (SEQ ID 619 751
NO: 607)
T46984_PEA_1_T47 (SEQ ID 619 751
NO: 609)
T46984_PEA_1_T48 (SEQ ID 619 751
NO: 610)

Segment cluster T46984_PEA—1_node—14 (SEQ ID NO:618) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T48 (SEQ ID NO:610). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T48 (SEQ ID 795 1718
NO: 610)

Segment cluster T46984_PEA—1_node—25 (SEQ ID NO:619) according to the present invention is supported by 257 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606) and T46984_PEA—1_T43 (SEQ ID NO:607). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1006 1171
T46984_PEA_1_T3 (SEQ ID NO: 594) 1006 1171
T46984_PEA_1_T12 (SEQ ID 1006 1171
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1006 1171
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1006 1171
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1006 1171
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1006 1171
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1006 1171
NO: 600)
T46984_PEA_1_T27 (SEQ ID 824 989
NO: 601)
T46984_PEA_1_T32 (SEQ ID 830 995
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1006 1171
NO: 603)
T46984_PEA_1_T35 (SEQ ID 734 899
NO: 604)
T46984_PEA_1_T40 (SEQ ID 1006 1171
NO: 605)
T46984_PEA_1_T42 (SEQ ID 1006 1171
NO: 606)
T46984_PEA_1_T43 (SEQ ID 1006 1171
NO: 607)

Segment cluster T46984_PEA—1_node—29 (SEQ ID NO:620) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T42 (SEQ ID NO:606). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T42 (SEQ ID 1302 1501
NO: 606)

Segment cluster T46984_PEA—1_node—34 (SEQ ID NO:621) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T40 (SEQ ID NO:605). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T40 (SEQ ID 1408 1717
NO: 605)

Segment cluster T46984_PEA—1_node—46 (SEQ ID NO:622) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T46 (SEQ ID NO:608). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T46 (SEQ ID 1 306
NO: 608)

Segment cluster T46984_PEA—1_node—47 (SEQ ID NO:623) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T19 (SEQ ID NO:599) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T3 (SEQ ID NO: 594) 1615 2242
T46984_PEA_1_T19 (SEQ ID 1615 2242
NO: 599)
T46984_PEA_1_T46 (SEQ ID 307 934
NO: 608)

Segment cluster T46984_PEA—1_node—52 (SEQ ID NO:624) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T19 (SEQ ID NO:599) and T46984_PEA—1_T23 (SEQ ID NO:600). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1838 2904
T46984_PEA_1_T19 (SEQ ID 2466 3532
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1838 2904
NO: 600)

Segment cluster T46984_PEA—1_node—65 (SEQ ID NO:625) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T51 (SEQ ID NO:611). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T51 (SEQ ID 1 348
NO: 611)

Segment cluster T46984_PEA—1_node—69 (SEQ ID NO:626) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T52 (SEQ ID 1 927
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1 927
NO: 613)

Segment cluster T46984_PEA—1_node—75 (SEQ ID NO:627) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T14 (SEQ ID NO:597). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T14 (SEQ ID 2199 3529
NO: 597)

Segment cluster T46984_PEA—1_node—86 (SEQ ID NO:628) according to the present invention is supported by 314 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3492 3750
T46984_PEA_1_T3 (SEQ ID NO: 594) 2886 3144
T46984_PEA_1_T12 (SEQ ID 2286 2544
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2317 2575
NO: 596)
T46984_PEA_1_T15 (SEQ ID 2175 2433
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4120 4378
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3396 3654
NO: 600)
T46984_PEA_1_T27 (SEQ ID 2076 2334
NO: 601)
T46984_PEA_1_T32 (SEQ ID 2082 2340
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1828 2086
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1986 2244
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1264 1522
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1578 1836
NO: 608)
T46984_PEA_1_T47 (SEQ ID 1017 1275
NO: 609)
T46984_PEA_1_T51 (SEQ ID 614 872
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1117 1375
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1117 1602
NO: 613)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster T46984_PEA—1_node—9 (SEQ ID NO:629) according to the present invention is supported by 304 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T47 (SEQ ID NO:609) and T46984_PEA—1_T48 (SEQ ID NO:610). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 523 618
T46984_PEA_1_T3 (SEQ ID NO: 594) 523 618
T46984_PEA_1_T12 (SEQ ID 523 618
NO: 595)
T46984_PEA_1_T13 (SEQ ID 523 618
NO: 596)
T46984_PEA_1_T14 (SEQ ID 523 618
NO: 597)
T46984_PEA_1_T15 (SEQ ID 523 618
NO: 598)
T46984_PEA_1_T19 (SEQ ID 523 618
NO: 599)
T46984_PEA_1_T23 (SEQ ID 523 618
NO: 600)
T46984_PEA_1_T27 (SEQ ID 341 436
NO: 601)
T46984_PEA_1_T32 (SEQ ID 523 618
NO: 602)
T46984_PEA_1_T34 (SEQ ID 523 618
NO: 603)
T46984_PEA_1_T40 (SEQ ID 523 618
NO: 605)
T46984_PEA_1_T42 (SEQ ID 523 618
NO: 606)
T46984_PEA_1_T43 (SEQ ID 523 618
NO: 607)
T46984_PEA_1_T47 (SEQ ID 523 618
NO: 609)
T46984_PEA_1_T48 (SEQ ID 523 618
NO: 610)

Segment cluster T46984_PEA—1_node—13 (SEQ ID NO:630) according to the present invention is supported by 232 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606), T46984_PEA—1_T43 (SEQ ID NO:607) and T46984_PEA—1_T48 (SEQ ID NO:610). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 752 794
T46984_PEA_1_T3 (SEQ ID NO: 594) 752 794
T46984_PEA_1_T12 (SEQ ID 752 794
NO: 595)
T46984_PEA_1_T13 (SEQ ID 752 794
NO: 596)
T46984_PEA_1_T14 (SEQ ID 752 794
NO: 597)
T46984_PEA_1_T15 (SEQ ID 752 794
NO: 598)
T46984_PEA_1_T19 (SEQ ID 752 794
NO: 599)
T46984_PEA_1_T23 (SEQ ID 752 794
NO: 600)
T46984_PEA_1_T27 (SEQ ID 570 612
NO: 601)
T46984_PEA_1_T34 (SEQ ID 752 794
NO: 603)
T46984_PEA_1_T40 (SEQ ID 752 794
NO: 605)
T46984_PEA_1_T42 (SEQ ID 752 794
NO: 606)
T46984_PEA_1_T43 (SEQ ID 752 794
NO: 607)
T46984_PEA_1_T48 (SEQ ID 752 794
NO: 610)

Segment cluster T46984_PEA—1_node—19 (SEQ ID NO:631) according to the present invention is supported by 237 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606) and T46984_PEA—1_T43 (SEQ ID NO:607). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 795 870
T46984_PEA_1_T3 (SEQ ID NO: 594) 795 870
T46984_PEA_1_T12 (SEQ ID 795 870
NO: 595)
T46984_PEA_1_T13 (SEQ ID 795 870
NO: 596)
T46984_PEA_1_T14 (SEQ ID 795 870
NO: 597)
T46984_PEA_1_T15 (SEQ ID 795 870
NO: 598)
T46984_PEA_1_T19 (SEQ ID 795 870
NO: 599)
T46984_PEA_1_T23 (SEQ ID 795 870
NO: 600)
T46984_PEA_1_T27 (SEQ ID 613 688
NO: 601)
T46984_PEA_1_T32 (SEQ ID 619 694
NO: 602)
T46984_PEA_1_T34 (SEQ ID 795 870
NO: 603)
T46984_PEA_1_T35 (SEQ ID 523 598
NO: 604)
T46984_PEA_1_T40 (SEQ ID 795 870
NO: 605)
T46984_PEA_1_T42 (SEQ ID 795 870
NO: 606)
T46984_PEA_1_T43 (SEQ ID 795 870
NO: 607)

Segment cluster T46984_PEA—1_node—21 (SEQ ID NO:632) according to the present invention is supported by 242 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606) and T46984_PEA—1_T43 (SEQ ID NO:607). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 871 975
T46984_PEA_1_T3 (SEQ ID NO: 594) 871 975
T46984_PEA_1_T12 (SEQ ID 871 975
NO: 595)
T46984_PEA_1_T13 (SEQ ID 871 975
NO: 596)
T46984_PEA_1_T14 (SEQ ID 871 975
NO: 597)
T46984_PEA_1_T15 (SEQ ID 871 975
NO: 598)
T46984_PEA_1_T19 (SEQ ID 871 975
NO: 599)
T46984_PEA_1_T23 (SEQ ID 871 975
NO: 600)
T46984_PEA_1_T27 (SEQ ID 689 793
NO: 601)
T46984_PEA_1_T32 (SEQ ID 695 799
NO: 602)
T46984_PEA_1_T34 (SEQ ID 871 975
NO: 603)
T46984_PEA_1_T35 (SEQ ID 599 703
NO: 604)
T46984_PEA_1_T40 (SEQ ID 871 975
NO: 605)
T46984_PEA_1_T42 (SEQ ID 871 975
NO: 606)
T46984_PEA_1_T43 (SEQ ID 871 975
NO: 607)

Segment cluster T46984_PEA—1_node—22 (SEQ ID NO:633) according to the present invention is supported by 205 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605), T46984_PEA—1_T42 (SEQ ID NO:606) and T46984_PEA—1_T43 (SEQ ID NO:607). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 976 1005
T46984_PEA_1_T3 (SEQ ID NO: 594) 976 1005
T46984_PEA_1_T12 (SEQ ID 976 1005
NO: 595)
T46984_PEA_1_T13 (SEQ ID 976 1005
NO: 596)
T46984_PEA_1_T14 (SEQ ID 976 1005
NO: 597)
T46984_PEA_1_T15 (SEQ ID 976 1005
NO: 598)
T46984_PEA_1_T19 (SEQ ID 976 1005
NO: 599)
T46984_PEA_1_T23 (SEQ ID 976 1005
NO: 600)
T46984_PEA_1_T27 (SEQ ID 794 823
NO: 601)
T46984_PEA_1_T32 (SEQ ID 800 829
NO: 602)
T46984_PEA_1_T34 (SEQ ID 976 1005
NO: 603)
T46984_PEA_1_T35 (SEQ ID 704 733
NO: 604)
T46984_PEA_1_T40 (SEQ ID 976 1005
NO: 605)
T46984_PEA_1_T42 (SEQ ID 976 1005
NO: 606)
T46984_PEA_1_T43 (SEQ ID 976 1005
NO: 607)

Segment cluster T46984_PEA—1_node—26 (SEQ ID NO:634) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605) and T46984_PEA—1_T42 (SEQ ID NO:606). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1172 1182
T46984_PEA_1_T3 (SEQ ID NO: 594) 1172 1182
T46984_PEA_1_T12 (SEQ ID 1172 1182
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1172 1182
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1172 1182
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1172 1182
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1172 1182
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1172 1182
NO: 600)
T46984_PEA_1_T27 (SEQ ID 990 1000
NO: 601)
T46984_PEA_1_T32 (SEQ ID 996 1006
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1172 1182
NO: 603)
T46984_PEA_1_T35 (SEQ ID 900 910
NO: 604)
T46984_PEA_1_T40 (SEQ ID 1172 1182
NO: 605)
T46984_PEA_1_T42 (SEQ ID 1172 1182
NO: 606)

Segment cluster T46984_PEA—1_node—28 (SEQ ID NO:635) according to the present invention is supported by 242 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T40 (SEQ ID NO:605) and T46984_PEA—1_T42 (SEQ ID NO:606). Table 69 below describes the starting and ending position of this segment on each transcript.

TABLE 69
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1183 1301
T46984_PEA_1_T3 (SEQ ID NO: 594) 1183 1301
T46984_PEA_1_T12 (SEQ ID 1183 1301
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1183 1301
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1183 1301
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1183 1301
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1183 1301
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1183 1301
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1001 1119
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1007 1125
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1183 1301
NO: 603)
T46984_PEA_1_T35 (SEQ ID 911 1029
NO: 604)
T46984_PEA_1_T40 (SEQ ID 1183 1301
NO: 605)
T46984_PEA_1_T42 (SEQ ID 1183 1301
NO: 606)

Segment cluster T46984_PEA—1_node—31 (SEQ ID NO:636) according to the present invention is supported by 207 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T40 (SEQ ID NO:605). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1302 1329
T46984_PEA_1_T3 (SEQ ID NO: 594) 1302 1329
T46984_PEA_1_T12 (SEQ ID 1302 1329
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1302 1329
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1302 1329
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1302 1329
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1302 1329
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1302 1329
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1120 1147
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1126 1153
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1302 1329
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1030 1057
NO: 604)
T46984_PEA_1_T40 (SEQ ID 1302 1329
NO: 605)

Segment cluster T46984_PEA—1_node—32 (SEQ ID NO:637) according to the present invention is supported by 226 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T40 (SEQ ID NO:605). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1330 1407
T46984_PEA_1_T3 (SEQ ID NO: 594) 1330 1407
T46984_PEA_1_T12 (SEQ ID 1330 1407
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1330 1407
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1330 1407
NO: 597)
T46984_PEA_1_T19 (SEQ ID 1330 1407
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1330 1407
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1148 1225
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1154 1231
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1330 1407
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1058 1135
NO: 604)
T46984_PEA_1_T40 (SEQ ID 1330 1407
NO: 605)

Segment cluster T46984_PEA—1_node—38 (SEQ ID NO:638) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603) and T46984_PEA—1_T35 (SEQ ID NO:604). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1408 1412
T46984_PEA_1_T3 (SEQ ID NO: 594) 1408 1412
T46984_PEA_1_T12 (SEQ ID 1408 1412
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1408 1412
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1408 1412
NO: 597)
T46984_PEA_1_T19 (SEQ ID 1408 1412
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1408 1412
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1226 1230
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1232 1236
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1408 1412
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1136 1140
NO: 604)

Segment cluster T46984_PEA—1_node—39 (SEQ ID NO:639) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603) and T46984_PEA—1_T35 (SEQ ID NO:604). Table 73 below describes the starting and ending position of this segment on each transcript.

TABLE 73
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1413 1435
T46984_PEA_1_T3 (SEQ ID NO: 594) 1413 1435
T46984_PEA_1_T12 (SEQ ID 1413 1435
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1413 1435
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1413 1435
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1330 1352
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1413 1435
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1413 1435
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1231 1253
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1237 1259
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1413 1435
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1141 1163
NO: 604)

Segment cluster T46984_PEA—1_node—40 (SEQ ID NO:640) according to the present invention is supported by 227 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603) and T46984_PEA—1_T35 (SEQ ID NO:604). Table 74 below describes the starting and ending position of this segment on each transcript.

TABLE 74
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1436 1499
T46984_PEA_1_T3 (SEQ ID NO: 594) 1436 1499
T46984_PEA_1_T12 (SEQ ID 1436 1499
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1436 1499
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1436 1499
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1353 1416
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1436 1499
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1436 1499
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1254 1317
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1260 1323
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1436 1499
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1164 1227
NO: 604)

Segment cluster T46984_PEA—1_node—42 (SEQ ID NO:641) according to the present invention is supported by 239 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603) and T46984_PEA—1_T35 (SEQ ID NO:604). Table 75 below describes the starting and ending position of this segment on each transcript.

TABLE 75
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1500 1562
T46984_PEA_1_T3 (SEQ ID NO: 594) 1500 1562
T46984_PEA_1_T12 (SEQ ID 1500 1562
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1500 1562
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1500 1562
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1417 1479
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1500 1562
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1500 1562
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1318 1380
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1324 1386
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1500 1562
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1228 1290
NO: 604)

Segment cluster T46984_PEA—1_node—43 (SEQ ID NO:642) according to the present invention is supported by 235 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602) and T46984_PEA—1_T35 (SEQ ID NO:604). Table 76 below describes the starting and ending position of this segment on each transcript.

TABLE 76
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1563 1614
T46984_PEA_1_T3 (SEQ ID NO: 594) 1563 1614
T46984_PEA_1_T12 (SEQ ID 1563 1614
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1563 1614
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1563 1614
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1480 1531
NO: 598)
T46984_PEA_1_T19 (SEQ ID 1563 1614
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1563 1614
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1381 1432
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1387 1438
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1291 1342
NO: 604)

Segment cluster T46984_PEA—1_node—48 (SEQ ID NO:643) according to the present invention is supported by 282 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 77 below describes the starting and ending position of this segment on each transcript.

TABLE 77
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1615 1715
T46984_PEA_1_T3 (SEQ ID NO: 594) 2243 2343
T46984_PEA_1_T12 (SEQ ID 1615 1715
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1615 1715
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1615 1715
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1532 1632
NO: 598)
T46984_PEA_1_T19 (SEQ ID 2243 2343
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1615 1715
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1433 1533
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1439 1539
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1343 1443
NO: 604)
T46984_PEA_1_T46 (SEQ ID 935 1035
NO: 608)

Segment cluster T46984_PEA—1_node—49 (SEQ ID NO:644) according to the present invention is supported by 262 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 78 below describes the starting and ending position of this segment on each transcript.

TABLE 78
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1716 1757
T46984_PEA_1_T3 (SEQ ID NO: 594) 2344 2385
T46984_PEA_1_T12 (SEQ ID 1716 1757
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1716 1757
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1716 1757
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1633 1674
NO: 598)
T46984_PEA_1_T19 (SEQ ID 2344 2385
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1716 1757
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1534 1575
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1540 1581
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1444 1485
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1036 1077
NO: 608)

Segment cluster T46984_PEA—1_node—50 (SEQ ID NO:645) according to the present invention is supported by 277 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 79 below describes the starting and ending position of this segment on each transcript.

TABLE 79
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1758 1809
T46984_PEA_1_T3 (SEQ ID NO: 594) 2386 2437
T46984_PEA_1_T12 (SEQ ID 1758 1809
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1758 1809
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1758 1809
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1675 1726
NO: 598)
T46984_PEA_1_T19 (SEQ ID 2386 2437
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1758 1809
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1576 1627
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1582 1633
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1486 1537
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1078 1129
NO: 608)

Segment cluster T46984_PEA—1_node—51 (SEQ ID NO:646) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T19 (SEQ ID NO:599) and T46984_PEA—1_T23 (SEQ ID NO:600). Table 80 below describes the starting and ending position of this segment on each transcript.

TABLE 80
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 1810 1837
T46984_PEA_1_T12 (SEQ ID 1810 1837
NO: 595)
T46984_PEA_1_T19 (SEQ ID 2438 2465
NO: 599)
T46984_PEA_1_T23 (SEQ ID 1810 1837
NO: 600)

Segment cluster T46984_PEA—1_node—53 (SEQ ID NO:647) according to the present invention is supported by 16 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T19 (SEQ ID NO:599) and T46984_PEA—1T23 (SEQ ID NO:600). Table 81 below describes the starting and ending position of this segment on each transcript.

TABLE 81
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 2905 2963
T46984_PEA_1_T13 (SEQ ID 1810 1868
NO: 596)
T46984_PEA_1_T19 (SEQ ID 3533 3591
NO: 599)
T46984_PEA_1_T23 (SEQ ID 2905 2963
NO: 600)

Segment cluster T46984_PEA—1_node—54 (SEQ ID NO:648) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T19 (SEQ ID NO:599) and T46984_PEA—1_T23 (SEQ ID NO:600). Table 82 below describes the starting and ending position of this segment on each transcript.

TABLE 82
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 2964 3043
T46984_PEA_1_T19 (SEQ ID 3592 3671
NO: 599)
T46984_PEA_1_T23 (SEQ ID 2964 3043
NO: 600)

Segment cluster T46984_PEA—1_node—55 (SEQ ID NO:649) according to the present invention is supported by 335 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1—T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 83 below describes the starting and ending position of this segment on each transcript.

TABLE 83
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3044 3110
T46984_PEA_1_T3 (SEQ ID NO: 594) 2438 2504
T46984_PEA_1_T12 (SEQ ID 1838 1904
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1869 1935
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1810 1876
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1727 1793
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3672 3738
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3044 3110
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1628 1694
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1634 1700
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1538 1604
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1130 1196
NO: 608)

Segment cluster T46984_PEA—1_node—57 (SEQ ID NO:650) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 84 below describes the starting and ending position of this segment on each transcript.

TABLE 84
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3111 3130
T46984_PEA_1_T3 (SEQ ID NO: 594) 2505 2524
T46984_PEA_1_T12 (SEQ ID 1905 1924
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1936 1955
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1877 1896
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1794 1813
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3739 3758
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3111 3130
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1695 1714
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1701 1720
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1605 1624
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1197 1216
NO: 608)

Segment cluster T46984_PEA—1_node—60 (SEQ ID NO:651) according to the present invention is supported by 326 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 85 below describes the starting and ending position of this segment on each transcript.

TABLE 85
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3131 3165
T46984_PEA_1_T3 (SEQ ID NO: 594) 2525 2559
T46984_PEA_1_T12 (SEQ ID 1925 1959
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1956 1990
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1897 1931
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1814 1848
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3759 3793
NO: 599)
T46984_PEA_1_T27 (SEQ ID 1715 1749
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1721 1755
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1625 1659
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1217 1251
NO: 608)

Segment cluster T46984_PEA—1_node—62 (SEQ ID NO:652) according to the present invention is supported by 335 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T35 (SEQ ID NO:604) and T46984_PEA—1_T46 (SEQ ID NO:608). Table 86 below describes the starting and ending position of this segment on each transcript.

TABLE 86
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3166 3226
T46984_PEA_1_T3 (SEQ ID NO: 594) 2560 2620
T46984_PEA_1_T12 (SEQ ID 1960 2020
NO: 595)
T46984_PEA_1_T13 (SEQ ID 1991 2051
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1932 1992
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1849 1909
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3794 3854
NO: 599)
T46984_PEA_1_T27 (SEQ ID 1750 1810
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1756 1816
NO: 602)
T46984_PEA_1_T35 (SEQ ID 1660 1720
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1252 1312
NO: 608)

Segment cluster T46984_PEA—1_node—66 (SEQ ID NO:653) according to the present invention is supported by 336 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609) and T46984_PEA—1_T51 (SEQ ID NO:611). Table 87 below describes the starting and ending position of this segment on each transcript.

TABLE 87
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3227 3261
T46984_PEA_1_T3 (SEQ ID NO: 594) 2621 2655
T46984_PEA_1_T12 (SEQ ID 2021 2055
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2052 2086
NO: 596)
T46984_PEA_1_T14 (SEQ ID 1993 2027
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1910 1944
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3855 3889
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3131 3165
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1811 1845
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1817 1851
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1563 1597
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1721 1755
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1313 1347
NO: 608)
T46984_PEA_1_T47 (SEQ ID 752 786
NO: 609)
T46984_PEA_1_T51 (SEQ ID 349 383
NO: 611)

Segment cluster T46984_PEA—1_node—67 (SEQ ID NO:654) according to the present invention is supported by 323 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609) and T46984_PEA—1_T51 (SEQ ID NO:611). Table 88 below describes the starting and ending position of this segment on each transcript.

TABLE 88
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3262 3302
T46984_PEA_1_T3 (SEQ ID NO: 594) 2656 2696
T46984_PEA_1_T12 (SEQ ID 2056 2096
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2087 2127
NO: 596)
T46984_PEA_1_T14 (SEQ ID 2028 2068
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1945 1985
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3890 3930
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3166 3206
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1846 1886
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1852 1892
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1598 1638
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1756 1796
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1348 1388
NO: 608)
T46984_PEA_1_T47 (SEQ ID 787 827
NO: 609)
T46984_PEA_1_T51 (SEQ ID 384 424
NO: 611)

Segment cluster T46984_PEA—1_node—70 (SEQ ID NO:655) according to the present invention is supported by 337 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 89 below describes the starting and ending position of this segment on each transcript.

TABLE 89
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3303 3377
T46984_PEA_1_T3 (SEQ ID NO: 594) 2697 2771
T46984_PEA_1_T12 (SEQ ID 2097 2171
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2128 2202
NO: 596)
T46984_PEA_1_T14 (SEQ ID 2069 2143
NO: 597)
T46984_PEA_1_T15 (SEQ ID 1986 2060
NO: 598)
T46984_PEA_1_T19 (SEQ ID 3931 4005
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3207 3281
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1887 1961
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1893 1967
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1639 1713
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1797 1871
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1389 1463
NO: 608)
T46984_PEA_1_T47 (SEQ ID 828 902
NO: 609)
T46984_PEA_1_T51 (SEQ ID 425 499
NO: 611)
T46984_PEA_1_T52 (SEQ ID 928 1002
NO: 612)
T46984_PEA_1_T54 (SEQ ID 928 1002
NO: 613)

Segment cluster T46984_PEA—1_node—71 (SEQ ID NO:656) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 90 below describes the starting and ending position of this segment on each transcript.

TABLE 90
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3378 3399
T46984_PEA_1_T3 (SEQ ID NO: 594) 2772 2793
T46984_PEA_1_T12 (SEQ ID 2172 2193
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2203 2224
NO: 596)
T46984_PEA_1_T14 (SEQ ID 2144 2165
NO: 597)
T46984_PEA_1_T15 (SEQ ID 2061 2082
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4006 4027
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3282 3303
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1962 1983
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1968 1989
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1714 1735
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1872 1893
NO: 604)
T46984_PEA_1_T46 (SEQ ID 1464 1485
NO: 608)
T46984_PEA_1_T47 (SEQ ID 903 924
NO: 609)
T46984_PEA_1_T51 (SEQ ID 500 521
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1003 1024
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1003 1024
NO: 613)

Segment cluster T46984_PEA—1_node—72 (SEQ ID NO:657) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 91 below describes the starting and ending position of this segment on each transcript.

TABLE 91
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T46984_PEA_1_T2 (SEQ ID NO: 593) 3400 3421
T46984_PEA_1_T3 (SEQ ID NO: 594) 2794 2815
T46984_PEA_1_T12 (SEQ ID 2194 2215
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2225 2246
NO: 596)
T46984_PEA_1_T14 (SEQ ID 2166 2187
NO: 597)
T46984_PEA_1_T15 (SEQ ID 2083 2104
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4028 4049
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3304 3325
NO: 600)
T46984_PEA_1_T27 (SEQ ID 1984 2005
NO: 601)
T46984_PEA_1_T32 (SEQ ID 1990 2011
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1736 1757
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1894 1915
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1172 1193
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1486 1507
NO: 608)
T46984_PEA_1_T47 (SEQ ID 925 946
NO: 609)
T46984_PEA_1_T51 (SEQ ID 522 543
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1025 1046
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1025 1046
NO: 613)

Segment cluster T46984_PEA—1_node—73 (SEQ ID NO:658) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 92 below describes the starting and ending position of this segment on each transcript.

TABLE 92
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T2 3422 3428
(SEQ ID NO: 593)
T46984_PEA_1_T3 2816 2822
(SEQ ID NO: 594)
T46984_PEA_1_T12 (SEQ ID 2216 2222
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2247 2253
NO: 596)
T46984_PEA_1_T14 (SEQ ID 2188 2194
NO: 597)
T46984_PEA_1_T15 (SEQ ID 2105 2111
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4050 4056
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3326 3332
NO: 600)
T46984_PEA_1_T27 (SEQ ID 2006 2012
NO: 601)
T46984_PEA_1_T32 (SEQ ID 2012 2018
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1758 1764
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1916 1922
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1194 1200
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1508 1514
NO: 608)
T46984_PEA_1_T47 (SEQ ID 947 953
NO: 609)
T46984_PEA_1_T51 (SEQ ID 544 550
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1047 1053
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1047 1053
NO: 613)

Segment cluster T46984_PEA—1_node—74 (SEQ ID NO:659) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T14 (SEQ ID NO:597), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 93 below describes the starting and ending position of this segment on each transcript.

TABLE 93
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T2 3429 3432
(SEQ ID NO: 593)
T46984_PEA_1_T3 2823 2826
(SEQ ID NO: 594)
T46984_PEA_1_T12 (SEQ ID 2223 2226
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2254 2257
NO: 596)
T46984_PEA_1_T14 (SEQ ID 2195 2198
NO: 597)
T46984_PEA_1_T15 (SEQ ID 2112 2115
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4057 4060
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3333 3336
NO: 600)
T46984_PEA_1_T27 (SEQ ID 2013 2016
NO: 601)
T46984_PEA_1_T32 (SEQ ID 2019 2022
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1765 1768
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1923 1926
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1201 1204
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1515 1518
NO: 608)
T46984_PEA_1_T47 (SEQ ID 954 957
NO: 609)
T46984_PEA_1_T51 (SEQ ID 551 554
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1054 1057
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1054 1057
NO: 613)

Segment cluster T46984_PEA—1_node—83 (SEQ ID NO:660) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 94 below describes the starting and ending position of this segment on each transcript.

TABLE 94
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T2 (SEQ ID NO: 3433 3437
593)
T46984_PEA_1_T3 (SEQ ID NO: 2827 2831
594)
T46984_PEA_1_T12 (SEQ ID 2227 2231
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2258 2262
NO: 596)
T46984_PEA_1_T15 (SEQ ID 2116 2120
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4061 4065
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3337 3341
NO: 600)
T46984_PEA_1_T27 (SEQ ID 2017 2021
NO: 601)
T46984_PEA_1_T32 (SEQ ID 2023 2027
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1769 1773
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1927 1931
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1205 1209
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1519 1523
NO: 608)
T46984_PEA_1_T47 (SEQ ID 958 962
NO: 609)
T46984_PEA_1_T51 (SEQ ID 555 559
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1058 1062
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1058 1062
NO: 613)

Segment cluster T46984_PEA—1_node—84 (SEQ ID NO:661) according to the present invention can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 95 below describes the starting and ending position of this segment on each transcript.

TABLE 95
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T2 (SEQ ID NO: 3438 3451
593)
T46984_PEA_1_T3 (SEQ ID NO: 2832 2845
594)
T46984_PEA_1_T12 (SEQ ID 2232 2245
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2263 2276
NO: 596)
T46984_PEA_1_T15 (SEQ ID 2121 2134
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4066 4079
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3342 3355
NO: 600)
T46984_PEA_1_T27 (SEQ ID 2022 2035
NO: 601)
T46984_PEA_1_T32 (SEQ ID 2028 2041
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1774 1787
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1932 1945
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1210 1223
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1524 1537
NO: 608)
T46984_PEA_1_T47 (SEQ ID 963 976
NO: 609)
T46984_PEA_1_T51 (SEQ ID 560 573
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1063 1076
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1063 1076
NO: 613)

Segment cluster T46984_PEA—1_node—85 (SEQ ID NO:662) according to the present invention is supported by 295 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T46984_PEA—1_T2 (SEQ ID NO:593), T46984_PEA—1_T3 (SEQ ID NO:594), T46984_PEA—1_T12 (SEQ ID NO:595), T46984_PEA—1_T13 (SEQ ID NO:596), T46984_PEA—1_T15 (SEQ ID NO:598), T46984_PEA—1_T19 (SEQ ID NO:599), T46984_PEA—1_T23 (SEQ ID NO:600), T46984_PEA—1_T27 (SEQ ID NO:601), T46984_PEA—1_T32 (SEQ ID NO:602), T46984_PEA—1_T34 (SEQ ID NO:603), T46984_PEA—1_T35 (SEQ ID NO:604), T46984_PEA—1_T43 (SEQ ID NO:607), T46984_PEA—1_T46 (SEQ ID NO:608), T46984_PEA—1_T47 (SEQ ID NO:609), T46984_PEA—1_T51 (SEQ ID NO:611), T46984_PEA—1_T52 (SEQ ID NO:612) and T46984_PEA—1_T54 (SEQ ID NO:613). Table 96 below describes the starting and ending position of this segment on each transcript.

TABLE 96
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T46984_PEA_1_T2 (SEQ ID NO: 3452 3491
593)
T46984_PEA_1_T3 (SEQ ID NO: 2846 2885
594)
T46984_PEA_1_T12 (SEQ ID 2246 2285
NO: 595)
T46984_PEA_1_T13 (SEQ ID 2277 2316
NO: 596)
T46984_PEA_1_T15 (SEQ ID 2135 2174
NO: 598)
T46984_PEA_1_T19 (SEQ ID 4080 4119
NO: 599)
T46984_PEA_1_T23 (SEQ ID 3356 3395
NO: 600)
T46984_PEA_1_T27 (SEQ ID 2036 2075
NO: 601)
T46984_PEA_1_T32 (SEQ ID 2042 2081
NO: 602)
T46984_PEA_1_T34 (SEQ ID 1788 1827
NO: 603)
T46984_PEA_1_T35 (SEQ ID 1946 1985
NO: 604)
T46984_PEA_1_T43 (SEQ ID 1224 1263
NO: 607)
T46984_PEA_1_T46 (SEQ ID 1538 1577
NO: 608)
T46984_PEA_1_T47 (SEQ ID 977 1016
NO: 609)
T46984_PEA_1_T51 (SEQ ID 574 613
NO: 611)
T46984_PEA_1_T52 (SEQ ID 1077 1116
NO: 612)
T46984_PEA_1_T54 (SEQ ID 1077 1116
NO: 613)

Variant protein alignment to the previously known protein:

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P2 (SEQ ID NO:664)×RIB2_HUMAN (SEQ ID NO:663)

Alignment segment 1/1:

Quality: 4716.00
Escore: 0
Matching length: 498 Total length: 498
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
          ·         ·         ·         ·        ·
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
          ·         ·         ·         ·        ·
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
          ·         ·         ·         ·        ·
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
          ·         ·         ·         ·        ·
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
          ·         ·         ·         ·        ·
351 EVEGDNRYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPA 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EVEGDNRYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPA 400
          ·         ·         ·         ·        ·
401 KAKGTFIADSHQNFALFFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFV 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 KAKGTFIADSHQNFALFFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFV 450
          ·         ·         ·         ·
451 AEPDNKNVYKFELDTSERKIEFDSASGTYTLYLIIGDATLKNPILWNV 498
||||||||||||||||||||||||||||||||||||||||||||||||||
451 AEPDNKNVYKFELDTSERKIEFDSASGTYTLYLIIGDATLKNPILWNV 498

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P3 (SEQ ID NO:665)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 4085.00
Escore: 0
Matching length: 433 Total length: 433
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P10 (SEQ ID NO:666)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 4716.00
Escore: 0
Matching length: 498 Total length: 498
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
          ·         ·         ·         ·        ·
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
          ·         ·         ·         ·        ·
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
          ·         ·         ·         ·        ·
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
          ·         ·         ·         ·        ·
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
          ·         ·         ·         ·        ·
351 EVEGDNRYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPA 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EVEGDNRYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPA 400
          ·         ·         ·         ·        ·
401 KAKGTFIADSHQNFALFFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFV 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 KAKGTFIADSHQNFALFFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFV 450
          ·         ·         ·         ·
451 AEPDNKNVYKFELDTSERKIEFDSASGTYTLYLIIGDATLKNPILWNV 498
||||||||||||||||||||||||||||||||||||||||||||||||||
451 AEPDNKNVYKFELDTSERKIEFDSASGTYTLYLIIGDATLKNPILWNV 498

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P11 (SEQ ID NO:667)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 5974.00
Escore: 0
Matching length: 628 Total length: 628
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P12 (SEQ ID NO:668)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 3179.00
Escore: 0
Matching length: 338 Total length: 338
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P21 (SEQ ID NO:669)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 5348.00
Escore: 0
Matching length: 562 Total length: 562
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

          ·         ·         ·         ·         ·
2 KACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSED 51
||||||||||||||||||||||||||||||||||||||||||||||||||
70 KACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSED 119
          ·         ·         ·         ·         ·
52 SSVTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTAS 101
||||||||||||||||||||||||||||||||||||||||||||||||||
120 SSVTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTAS 169
          ·         ·         ·         ·         ·
102 HLSQQADLRSIVEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLM 151
||||||||||||||||||||||||||||||||||||||||||||||||||
170 HLSQQADLRSIVEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLM 219
          ·         ·         ·         ·         ·
152 DHVGTEPSIKEDQVIQLMNAIFSKKNFESLSEAFSVASAAAVLSHNRYHV 201
||||||||||||||||||||||||||||||||||||||||||||||||||
220 DHVGTEPSIKEDQVIQLMNAIFSKKNFESLSEAFSVASAAAVLSHNRYHV 269
          ·         ·         ·         ·         ·
202 PVVVVPEGSASDTHEQAILRLQVTNVLSQPLTQATVKLEHAKSVASRATV 251
||||||||||||||||||||||||||||||||||||||||||||||||||
270 PVVVVPEGSASDTHEQAILRLQVTNVLSQPLTQATVKLEHAKSVASRATV 319
          ·         ·         ·         ·         ·
252 LQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIANTVELRVKI 301
||||||||||||||||||||||||||||||||||||||||||||||||||
320 LQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIANTVELRVKI 369
          ·         ·         ·         ·         ·
302 STEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQ 351
||||||||||||||||||||||||||||||||||||||||||||||||||
370 STEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQ 419
          ·         ·         ·         ·         ·
352 LVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERK 401
||||||||||||||||||||||||||||||||||||||||||||||||||
420 LVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERK 469
          ·         ·         ·         ·         ·
402 IEFDSASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNL 451
||||||||||||||||||||||||||||||||||||||||||||||||||
470 IEFDSASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNL 519
          ·         ·         ·         ·         ·
452 FTPKQEIQHLFREPEKRPPTVVSNTFTALILSPLLLLFALWIRIGANVSN 501
||||||||||||||||||||||||||||||||||||||||||||||||||
520 FTPKQEIQHLFREPEKRPPTVVSNTFTALILSPLLLLFALWIRIGANVSN 569
          ·         ·         ·         ·         ·
502 FTFAPSTIIFHLGHAAMLGLMYVYWTQLNMFQTLKYLAILGSVTFLAGNR 551
||||||||||||||||||||||||||||||||||||||||||||||||||
570 FTFAPSTIIFHLGHAAMLGLMYVYWTQLNMFQTLKYLAILGSVTFLAGNR 619
          ·
552 MLAQQAVKRTAH 563
||||||||||||
620 MLAQQAVKRTAH 631

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P27 (SEQ ID NO:670)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 3910.00
Escore: 0
Matching length: 415 Total length: 415
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
          ·         ·         ·         ·        ·
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
          ·         ·         ·         ·        ·
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
          ·         ·         ·         ·        ·
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
          ·         ·         ·         ·        ·
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
          ·         ·         ·         ·        ·
351 EVEGDNRYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPA 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 EVEGDNRYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPA 400
          ·
401 KAKGTFIADSHQNFA 415
|||||||||||||||
401 KAKGTFIADSHQNFA 415

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P32 (SEQ ID NO:671)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 3434.00
Escore: 0
Matching length: 373 Total length: 373
Matching Percent 98.93 Matching Percent Identity: 98.39
Similarity:
Total Percent Similarity: 98.93 Total Percent Identity: 98.39
Gaps: 0

Alignment

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
          ·         ·         ·         ·        ·
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
          ·         ·         ·         ·        ·
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
          ·         ·         ·         ·        ·
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
          ·         ·         ·         ·        ·
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLV 350
          ·         ·
351 EVEGDNRYIANTVEGQVRWLTPV 373
|||||||||||||| :|:  | |
351 EVEGDNRYIANTVELRVKISTEV 373

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P34 (SEQ ID NO:672)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 3087.00
Escore: 0
Matching length: 329 Total length: 329
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQTYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQTYHAVAALSGFGLPLASQEALSALTA 150
          ·         ·         ·         ·        ·
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
          ·         ·         ·         ·        ·
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
          ·         ·         ·         ·        ·
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL 300
          ·         ·
301 TQATVKLEHAKSVASRATVLQKTSFTPVG 329
|||||||||||||||||||||||||||||
301 TQATVKLEHAKSVASRATVLQKTSFTPVG 329

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P35 (SEQ ID NO:673)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 2697.00
Escore: 0
Matching length: 287 Total length: 287
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
          ·         ·         ·         ·        ·
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 RLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVARLDELGGVYLQ 200
          ·         ·         ·         ·        ·
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 FEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFESLS 250
          ·         ·         ·
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAI 287
|||||||||||||||||||||||||||||||||||||
251 EAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAI 287

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P38 (SEQ ID NO:674)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 1368.00
Escore: 0
Matching length: 145 Total length: 145
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEAL 145
|||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEAL 145

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P39 (SEQ ID NO:675)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 1500.00
Escore: 0
Matching length: 160 Total length: 160
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
          ·         ·         ·         ·        ·
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 EISISNETKDLLLAAVSEDSSVTQIYHAVAALSGFGLPLASQEALSALTA 150
          ·
151 RLSKEETVLA 160
||||||||||
151 RLSKEETVLA 160

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P45 (SEQ ID NO:676)×RIB2_HUMAN (SEQ ID NO:663)

Alignment segment 1/1:

Quality: 970.00
Escore: 0
Matching length: 103 Total length: 103
Matching Percent 99.03 Matching Percent Identity: 99.03
Similarity:
Total Percent Similarity: 99.03 Total Percent Identity: 99.03
Gaps: 0

Alignment

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·         ·         ·         ·        ·
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGC 100
101 ENS 103
| |
101 EIS 103

Sequence name: RIB2_HUMAN (SEQ ID NO:663)

Sequence documentation:

Alignment of: T46984_PEA—1_P46 (SEQ ID NO:677)×RIB2_HUMAN (SEQ ID NO:663).

Alignment segment 1/1:

Quality: 656.00
Escore: 0
Matching length: 69 Total length: 69
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment

          ·         ·         ·         ·        ·
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLES 50
          ·
51 AFYSIVGLSSLGAQVPDAK 69
|||||||||||||||||||
51 AFYSIVGLSSLGAQVPDAK 69

Description for Cluster T11628

Cluster T11628 features 6 transcript(s) and 25 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
T11628_PEA_1_T3 678
T11628_PEA_1_T4 679
T11628_PEA_1_T5 680
T11628_PEA_1_T7 681
T11628_PEA_1_T9 682
T11628_PEA_1_T11 683

TABLE 2
Segments of interest
Segment Name Sequence ID No.
T11628_PEA_1_node_7 684
T11628_PEA_1_node_11 685
T11628_PEA_1_node_16 686
T11628_PEA_1_node_22 687
T11628_PEA_1_node_25 688
T11628_PEA_1_node_31 689
T11628_PEA_1_node_37 690
T11628_PEA_1_node_0 691
T11628_PEA_1_node_4 692
T11628_PEA_1_node_9 693
T11628_PEA_1_node_13 694
T11628_PEA_1_node_14 695
T11628_PEA_1_node_17 696
T11628_PEA_1_node_18 697
T11628_PEA_1_node_19 698
T11628_PEA_1_node_24 699
T11628_PEA_1_node_27 700
T11628_PEA_1_node_28 701
T11628_PEA_1_node_29 702
T11628_PEA_1_node_30 703
T11628_PEA_1_node_32 704
T11628_PEA_1_node_33 705
T11628_PEA_1_node_34 706
T11628_PEA_1_node_35 707
T11628_PEA_1_node_36 708

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
T11628_PEA_1_P2 712 T11628_PEA_1_T3 (SEQ ID
NO: 678);
T11628_PEA_1_T5 (SEQ ID
NO: 680);
T11628_PEA_1_T7 (SEQ ID
NO: 681)
T11628_PEA_1_P5 713 T11628_PEA_1_T9 (SEQ ID
NO: 682)
T11628_PEA_1_P7 714 T11628_PEA_1_T11 (SEQ
ID NO: 683)
T11628_PEA_1_P10 715 T11628_PEA_1_T4 (SEQ ID
NO: 679)

These sequences are variants of the known protein Myoglobin (SwissProt accession identifier MYG_HUMAN), SEQ ID NO: 709, referred to herein as the previously known protein.

Protein Myoglobin (SEQ ID NO:709) is known or believed to have the following function(s): Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. The sequence for protein Myoglobin (SEQ ID NO:709) is given at the end of the application, as “Myoglobin (SEQ ID NO:709) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
54 E -> K. /FTId = VAR_003180.
133 K -> N. /FTId = VAR_003181.
139 R -> Q. /FTId = VAR_003182.
139 R -> W. /FTId = VAR_003183.
128 Q -> E

As noted above, cluster T11628 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Myoglobin (SEQ ID NO:709). A description of each variant protein according to the present invention is now provided.

Variant protein T11628_PEA—1_P2 (SEQ ID NO:712) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T11628_PEA—1_T3 (SEQ ID NO:678). An alignment is given to the known protein (Myoglobin (SEQ ID NO:709)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T11628_PEA—1_P2 (SEQ ID NO:712) and Q8WVH6 (SEQ ID NO:711) (SEQ ID NO:711):

1.An isolated chimeric polypeptide encoding for T11628_PEA—1—P2 (SEQ ID NO:712), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) corresponding to amino acids 1-55 of T11628_PEA—1_P2 (SEQ ID NO:712), and a second amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of Q8WVH6 (SEQ ID NO:711), which also corresponds to amino acids 56-154 of T11628_PEA—1_P2 (SEQ ID NO:712), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a head of T11628_PEA—1_P2 (SEQ ID NO:712), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956)
of T11628_PEA_1_P2. (SEQ ID NO:712)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein T11628_PEA—1_P2 (SEQ ID NO:712) also has the following non-silent SNPs(Single Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P2 (SEQ ID NO:712) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
26 G -> No
44 F -> No
92 Q -> R No
135 A -> No
141 K -> No
153 Q -> No

Variant protein T11628_PEA—1_P2 (SEQ ID NO:712) is encoded by the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T11628_PEA—1_T3 (SEQ ID NO:678) is shown in bold; this coding portion starts at position 220 and ends at position 681. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P2 (SEQ ID NO:712) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
83 G -> A Yes
93 G -> A Yes
95 G -> A Yes
146 G -> A Yes
295 G -> No
349 T -> No
393 G -> A Yes
423 C -> T Yes
494 A -> G No
498 G -> A No
623 C -> No
642 G -> No
678 G -> No
686 C -> No
686 C -> A No
717 C -> No
787 T -> G No
820 G -> T No
826 G -> T No
850 C -> No
934 T -> G No
975 A -> G Yes
1117 G -> No
1218 A -> G No

Variant protein T11628_PEA—1_P5 (SEQ ID NO:713) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T11628_PEA—1_T9 (SEQ ID NO:682). An alignment is given to the known protein (Myoglobin (SEQ ID NO:709) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T11628_PEA—1_P5 (SEQ ID NO:713) and MYG_HUMAN—V1 (SEQ ID NO:710):

1.An isolated chimeric polypeptide encoding for T11628_PEA—1_P5 (SEQ ID NO:713), comprising a first amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 56-154 of MYG_HUMAN_V1 (SEQ ID NO:710), which also corresponds to amino acids 1-99 of T11628_PEA—1_P5 (SEQ ID NO:713).

It should be noted that the known protein sequence (MYG_HUMAN (SEQ ID NO:709)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYG_HUMAN_V1 (SEQ ID NO: 710). These changes were previously known to occur and are listed in the table below.

TABLE 7
Changes to MYG_HUMAN_V1 (SEQ ID NO: 710)
SNP position(s) on
amino acid sequence Type of change
1 init_met

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein T11628_PEA—1_P5 (SEQ ID NO:713) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P5 (SEQ ID NO:713) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
37 Q -> R No
80 A -> No
86 K -> No
98 Q -> No

Variant protein T11628_PEA—1_P5 (SEQ ID NO:713) is encoded by the following Transcript(s): T11628_PEA—1_T9 (SEQ ID NO:682), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T11628_PEA—1_T9 (SEQ ID NO:682) is shown in bold; this coding portion starts at position 211 and ends at position 507. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P5 (SEQ ID NO:713) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
2 C -> T Yes
175 T -> No
219 G -> A Yes
249 C -> T Yes
320 A -> G No
324 G -> A No
449 C -> No
468 G -> No
504 G -> No
512 C -> No
512 C -> A No
543 C -> No
613 T -> G No
646 G -> T No
652 G -> T No
676 C -> No
760 T -> G No
801 A -> G Yes
943 G -> No
1044 A -> G No

Variant protein T11628_PEA—1_P7 (SEQ ID NO:714) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T11628_PEA—1_T11 (SEQ ID NO:683). An alignment is given to the known protein (Myoglobin (SEQ ID NO:709)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T11628_PEA—1_P7 (SEQ ID NO:714) and MYG _HUMAN_V1 (SEQ ID NO:710):

1. An isolated chimeric polypeptide encoding for T11628_PEA—1_P7 (SEQ ID NO:714), comprising a first amino acid sequence being at least 90% homologous to MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMK ASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQ SKHPGDFGADAQGAMNK corresponding to amino acids 1-134 of MYG_HUMAN_V1, which also corresponds to amino acids 1-134 of T11628_PEA—1_P7 (SEQ ID NO:714), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence G corresponding to amino acids 135-135 of T11628_PEA—1_P7 (SEQ ID NO:714), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

It should be noted that the known protein sequence (MYG_HUMAN (SEQ ID NO:709)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYG_HUMAN_V1 (SEQ ID NO:710). These changes were previously known to occur and are listed in the table below.

TABLE 10
Changes to MYG_HUMAN_V1 (SEQ ID NO: 710)
SNP position(s) on
amino acid sequence Type of change
1 init_met

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein T11628_PEA—1_P7 (SEQ ID NO:714) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P7 (SEQ ID NO:714) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
26 G -> No
44 F -> No
92 Q -> R No

Variant protein T11628_PEA—1_P7 (SEQ ID NO:714) is encoded by the following transcript(s): T11628_PEA—1_T11 (SEQ ID NO:683), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T11628_PEA—1_T11 (SEQ ID NO:683) is shown in bold; this coding portion starts at position 319 and ends at position 723. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P7 (SEQ ID NO:714) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
394 G -> No
448 T -> No
492 G -> A Yes
522 C -> T Yes
593 A -> G No
597 G -> A No
728 C -> No
728 C -> A No
759 C -> No
829 T -> G No
862 G -> T No
868 G -> T No
892 C -> No
976 T -> G No
1017 A -> G Yes
1159 G -> No
1260 A -> G No

Variant protein T11628_PEA—1_P10 (SEQ ID NO:715) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T11628_PEA—1_T4 (SEQ ID NO:679). An alignment is given to the known protein (Myoglobin (SEQ ID NO:709)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between T11628_PEA—1_P10 (SEQ ID NO:715) and Q8WVH6 (SEQ ID NO:711):

1.An isolated chimeric polypeptide encoding for T11628_PEA—1_P10 (SEQ ID NO:715), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) corresponding to amino acids 1-55 of T11628_PEA—1_P10 (SEQ ID NO:715), and a second amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of Q8WVH6 (SEQ ID NO:711), which also corresponds to amino acids 56-154 of T11628_PEA—1_P10 (SEQ ID NO:715), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a head of T11628_PEA—1_P10 (SEQ ID NO:715), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956)
of T11628_PEA_1_P10. (SEQ ID NO:715)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein T11628_PEA—1_P10 (SEQ ID NO:715) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P10 (SEQ ID NO:715) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
26 G -> No
44 F -> No
92 Q -> R No
135 A -> No
141 K -> No
153 Q -> No

Variant protein T11628_PEA—1_P10 (SEQ ID NO:715) is encoded by the following transcript(s): T11628_PEA—1_T4 (SEQ ID NO:679), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T11628_PEA—1_T4 (SEQ ID NO:679) is shown in bold; this coding portion starts at position 205 and ends at position 666. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T11628_PEA—1_P10 (SEQ ID NO:715) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
280 G -> No
334 T -> No
378 G -> A Yes
408 C -> T Yes
479 A -> G No
483 G -> A No
608 C -> No
627 G -> No
663 G -> No
671 C -> No
671 C -> A No
702 C -> No
772 T -> G No
805 G -> T No
811 G -> T No
835 C -> No
919 T -> G No
960 A -> G Yes
1102 G -> No
1203 A -> G No

As noted above, cluster T11628 features 25 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T11628_PEA—1_node—7 (SEQ ID NO:684) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T11628_PEA_1_T3 (SEQ ID NO: 1 211
678)

Segment cluster T11628_PEA—1_node—11 (SEQ ID NO:685) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T5 (SEQ ID NO:680). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T11628_PEA_1_T5 (SEQ ID NO: 48 178
680)

Segment cluster T11628_PEA—1_node—16 (SEQ ID NO:686) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T11 (SEQ ID NO:683). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T11628_PEA_1_T11 (SEQ ID 1 214
NO: 683)

Segment cluster T11628_PEA—1_node—22 (SEQ ID NO:687) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T9 (SEQ ID NO:682). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T11628_PEA_1_T9 (SEQ ID NO: 1 140
682)

Segment cluster T11628_PEA—1_node—25 (SEQ ID NO:688) according to the present invention is supported by 129 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 395 537
T11628_PEA_1_T4 (SEQ ID NO: 679) 380 522
T11628_PEA_1_T5 (SEQ ID NO: 680) 362 504
T11628_PEA_1_T7 (SEQ ID NO: 681) 347 489
T11628_PEA_1_T9 (SEQ ID NO: 682) 221 363
T11628_PEA_1_T11 (SEQ ID 494 636
NO: 683)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 20.

TABLE 20
Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
T11628_0_9_0 (SEQ ID breast malignant tumors BRS
NO: 911)

Segment cluster T11628_PEA—1_node—31 (SEQ ID NO:689) according to the present invention is supported by 137 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 702 831
T11628_PEA_1_T4 (SEQ ID NO: 679) 687 816
T11628_PEA_1_T5 (SEQ ID NO: 680) 669 798
T11628_PEA_1_T7 (SEQ ID NO: 681) 654 783
T11628_PEA_1_T9 (SEQ ID NO: 682) 528 657
T11628_PEA_1_T11 (SEQ ID 744 873
NO: 683)

Segment cluster T11628_PEA—1_node—37 (SEQ ID NO:690) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 1086 1225
T11628_PEA_1_T4 (SEQ ID NO: 679) 1071 1210
T11628_PEA_1_T5 (SEQ ID NO: 680) 1053 1192
T11628_PEA_1_T7 (SEQ ID NO: 681) 1038 1177
T11628_PEA_1_T9 (SEQ ID NO: 682) 912 1051
T11628_PEA_1_T11 (SEQ ID 1128 1267
NO: 683)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster T11628_PEA—1_node—0 (SEQ ID NO:691) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T4 (SEQ ID NO:679). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T4 (SEQ ID NO: 679) 1 93

Segment cluster T11628_PEA—1_node—4 (SEQ ID NO:692) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T4 (SEQ ID NO:679). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T4 (SEQ ID NO: 679) 94 196

Segment cluster T11628_PEA—1_node—9 (SEQ ID NO:693) according to the present invention is supported by 16 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T5 (SEQ ID NO:680) and T11628_PEA—1_T7 (SEQ ID NO:681). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T5 (SEQ ID NO: 680) 1 47
T11628_PEA_1_T7 (SEQ ID NO: 681) 1 47

Segment cluster T11628_PEA—1_node—13 (SEQ ID NO:694) according to the present invention can be found in the following transcript(s): T11628_PEA—1_T7 (SEQ ID NO:681). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T7 (SEQ ID NO: 681) 48 65

Segment cluster T11628_PEA—1_node—14 (SEQ ID NO:695) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T7 (SEQ ID NO:681). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T7 (SEQ ID NO: 681) 66 163

Segment cluster T11628_PEA—1_node—17 (SEQ ID NO:696) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T11 (SEQ ID NO:683). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
T11628_PEA_1_T11 (SEQ ID 215 310
NO: 683)

Segment cluster T11628_PEA—1_node—18 (SEQ ID NO:697) according to the present invention is supported by 98 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 212 289
T11628_PEA_1_T4 (SEQ ID NO: 679) 197 274
T11628_PEA_1_T5 (SEQ ID NO: 680) 179 256
T11628_PEA_1_T7 (SEQ ID NO: 681) 164 241
T11628_PEA_1_T11 (SEQ ID NO: 683) 311 388

Segment cluster T11628_PEA—1_node—19 (SEQ ID NO:698) according to the present invention can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681) and T11628_PEA—1_T11(SEQ ID NO:683). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 290 314
T11628_PEA_1_T4 (SEQ ID NO: 679) 275 299
T11628_PEA_1_T5 (SEQ ID NO: 680) 257 281
T11628_PEA_1_T7 (SEQ ID NO: 681) 242 266
T11628_PEA_1_T11 (SEQ ID NO: 683) 389 413

Segment cluster T11628_PEA—1_node—24 (SEQ ID NO:699) according to the present invention is supported by 112 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 315 394
T11628_PEA_1_T4 (SEQ ID NO: 679) 300 379
T11628_PEA_1_T5 (SEQ ID NO: 680) 282 361
T11628_PEA_1_T7 (SEQ ID NO: 681) 267 346
T11628_PEA_1_T9 (SEQ ID NO: 682) 141 220
T11628_PEA_1_T11 (SEQ ID 414 493
NO: 683)

Segment cluster T11628_PEA—1_node—27 (SEQ ID NO:700) according to the present invention is supported by 119 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 538 621
T11628_PEA_1_T4 (SEQ ID NO: 679) 523 606
T11628_PEA_1_T5 (SEQ ID NO: 680) 505 588
T11628_PEA_1_T7 (SEQ ID NO: 681) 490 573
T11628_PEA_1_T9 (SEQ ID NO: 682) 364 447
T11628_PEA_1_T11 (SEQ ID 637 720
NO: 683)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 33.

TABLE 33
Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
T11628_0_9_0 (SEQ ID breast malignant tumors BRS
NO: 911)

Segment cluster T11628_PEA—1_node—28 (SEQ ID NO:701) according to the present invention is supported by 115 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681) and T11628_PEA—1_T9 (SEQ ID NO:682). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 622 650
T11628_PEA_1_T4 (SEQ ID NO: 679) 607 635
T11628_PEA_1_T5 (SEQ ID NO: 680) 589 617
T11628_PEA_1_T7 (SEQ ID NO: 681) 574 602
T11628_PEA_1_T9 (SEQ ID NO: 682) 448 476

Segment cluster T11628_PEA—1_node—29 (SEQ ID NO:702) according to the present invention is supported by 113 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681) and T11628_PEA—1_T9 (SEQ ID NO:682). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 651 678
T11628_PEA_1_T4 (SEQ ID NO: 679) 636 663
T11628_PEA_1_T5 (SEQ ID NO: 680) 618 645
T11628_PEA_1_T7 (SEQ ID NO: 681) 603 630
T11628_PEA_1_T9 (SEQ ID NO: 682) 477 504

Segment cluster T11628_PEA—1_node—30 (SEQ ID NO:703) according to the present invention can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 679 701
T11628_PEA_1_T4 (SEQ ID NO: 679) 664 686
T11628_PEA_1_T5 (SEQ ID NO: 680) 646 668
T11628_PEA_1_T7 (SEQ ID NO: 681) 631 653
T11628_PEA_1_T9 (SEQ ID NO: 682) 505 527
T11628_PEA_1_T11 (SEQ ID 721 743
NO: 683)

Segment cluster T11628_PEA—1_node—32 (SEQ ID NO:704) according to the present invention can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 832 844
T11628_PEA_1_T4 (SEQ ID NO: 679) 817 829
T11628_PEA_1_T5 (SEQ ID NO: 680) 799 811
T11628_PEA_1_T7 (SEQ ID NO: 681) 784 796
T11628_PEA_1_T9 (SEQ ID NO: 682) 658 670
T11628_PEA_1_T11 (SEQ ID 874 886
NO: 683)

Segment cluster T11628_PEA—1_node—33 (SEQ ID NO:705) according to the present invention can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 845 866
T11628_PEA_1_T4 (SEQ ID NO: 679) 830 851
T11628_PEA_1_T5 (SEQ ID NO: 680) 812 833
T11628_PEA_1_T7 (SEQ ID NO: 681) 797 818
T11628_PEA_1_T9 (SEQ ID NO: 682) 671 692
T11628_PEA_1_T11 (SEQ ID 887 908
NO: 683)

Segment cluster T11628_PEA—1_node—34 (SEQ ID NO:706) according to the present invention is supported by 122 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 867 911
T11628_PEA_1_T4 (SEQ ID NO: 679) 852 896
T11628_PEA_1_T5 (SEQ ID NO: 680) 834 878
T11628_PEA_1_T7 (SEQ ID NO: 681) 819 863
T11628_PEA_1_T9 (SEQ ID NO: 682) 693 737
T11628_PEA_1_T11 (SEQ ID 909 953
NO: 683)

Segment cluster T11628_PEA—1_node—35 (SEQ ID NO:707) according to the present invention is supported by 126 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682 and T11628_PEA—1_T11 (SEQ ID NO:683). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 912 967
T11628_PEA_1_T4 (SEQ ID NO: 679) 897 952
T11628_PEA_1_T5 (SEQ ID NO: 680) 879 934
T11628_PEA_1_T7 (SEQ ID NO: 681) 864 919
T11628_PEA_1_T9 (SEQ ID NO: 682) 738 793
T11628_PEA_1_T11 (SEQ ID 954 1009
NO: 683)

Segment cluster T11628_PEA—1_node—36 (SEQ ID NO:708) according to the present invention is supported by 122 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T11628_PEA—1_T3 (SEQ ID NO:678), T11628_PEA—1_T4 (SEQ ID NO:679), T11628_PEA—1_T5 (SEQ ID NO:680), T11628_PEA—1_T7 (SEQ ID NO:681), T11628_PEA—1_T9 (SEQ ID NO:682) and T11628_PEA—1_T11 (SEQ ID NO:683). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41
Segment location on transcripts
Segment
Segment ending
Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 678) 968 1085
T11628_PEA_1_T4 (SEQ ID NO: 679) 953 1070
T11628_PEA_1_T5 (SEQ ID NO: 680) 935 1052
T11628_PEA_1_T7 (SEQ ID NO: 681) 920 1037
T11628_PEA_1_T9 (SEQ ID NO: 682) 794 911
T11628_PEA_1_T11 (SEQ ID 1010 1127
NO: 683)

Variant protein alignment to the previously known protein:

Sequence name: Q8WVH6 (SEQ ID NO:711)

Sequence documentation:

Alignment of: T11628_PEA—1_P2 (SEQ ID NO:712)×Q8WVH6 (SEQ ID NO:711).

Alignment segment 1/1:

Quality: 962.00
Escore: 0
Matching length: 99 Total length: 99
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
56 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 105
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 50
          ·         ·         ·         ·
106 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154
||||||||||||||||||||||||||||||||||||||||||||||||||
51 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 99

Sequence name: MYG_HUMAN_V1 (SEQ ID NO:710)

Sequence documentation:

Alignment of: T11628_PEA—1_P5 (SEQ ID NO:713)×MYG_HUMAN_V1 (SEQ ID NO:710).

Alignment segment 1/1:

Quality: 962.00
Escore: 0
Matching length: 99 Total length: 99
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
56 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 105
          ·         ·         ·         ·
51 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 99
||||||||||||||||||||||||||||||||||||||||||||||||||
106 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154

Sequence name: MYG_HUMAN_V1 (SEQ ID NO:710)

Sequence documentation:

Sequence of: T11628_PEA—1_P7 (SEQ ID NO:714)×MYG_HUMAN_V1 (SEQ ID NO:710).

Alignment segment 1/1:

Quality: 1315.00
Escore: 0
Matching length: 134 Total length: 134
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
1 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHL 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHL 50
          ·         ·         ·         ·        ·
51 KSEDEMKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKI 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 KSEDEMKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKI 100
          ·         ·         ·
101 PVKYLEFISECIIQVLQSKHPGDFGADAQGAMNK 134
||||||||||||||||||||||||||||||||||
101 PVKYLEFISECIIQVLQSKHPGDFGADAQGAMNK 134

Sequence name: Q8WVH6 (SEQ ID NO:711)

Sequence documentation:

Alignment of: T11628_PEA—1_P10 (SEQ ID NO:715)×Q8WVH6 (SEQ ID NO:711).

Alignment segment 1/1:

Quality: 962.00
Escore: 0
Matching length: 99 Total length: 99
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

          ·         ·         ·         ·        ·
56 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 105
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYL 50
          ·         ·         ·         ·
106 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154
||||||||||||||||||||||||||||||||||||||||||||||||||
51 EFISECIIQVLQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG 99

Description for Cluster M78076

Cluster M78076 features 9 transcript(s) and 35 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
M78076_PEA_1_T2 716
M78076_PEA_1_T3 717
M78076_PEA_1_T5 718
M78076_PEA_1_T13 719
M78076_PEA_1_T15 720
M78076_PEA_1_T23 721
M78076_PEA_1_T26 722
M78076_PEA_1_T27 723
M78076_PEA_1_T28 724

TABLE 2
Segments of interest
Segment Name Sequence ID No.
M78076_PEA_1_node_0 725
M78076_PEA_1_node_10 726
M78076_PEA_1_node_15 727
M78076_PEA_1_node_18 728
M78076_PEA_1_node_20 729
M78076_PEA_1_node_24 730
M78076_PEA_1_node_26 731
M78076_PEA_1_node_29 732
M78076_PEA_1_node_32 733
M78076_PEA_1_node_35 734
M78076_PEA_1_node_37 735
M78076_PEA_1_node_46 736
M78076_PEA_1_node_47 737
M78076_PEA_1_node_54 738
M78076_PEA_1_node_1 739
M78076_PEA_1_node_2 740
M78076_PEA_1_node_3 741
M78076_PEA_1_node_6 742
M78076_PEA_1_node_7 743
M78076_PEA_1_node_12 744
M78076_PEA_1_node_22 745
M78076_PEA_1_node_27 746
M78076_PEA_1_node_30 747
M78076_PEA_1_node_31 748
M78076_PEA_1_node_34 749
M78076_PEA_1_node_36 750
M78076_PEA_1_node_41 751
M78076_PEA_1_node_42 752
M78076_PEA_1_node_43 753
M78076_PEA_1_node_45 754
M78076_PEA_1_node_49 755
M78076_PEA_1_node_50 756
M78076_PEA_1_node_51 757
M78076_PEA_1_node_52 758
M78076_PEA_1_node_53 759

TABLE 3
Proteins of interest
Sequence
Protein Name ID No. Corresponding Transcript(s)
M78076_PEA_1_P3 761 M78076_PEA_1_T2 (SEQ ID
NO: 716);
M78076_PEA_1_T5 (SEQ ID
NO: 718)
M78076_PEA_1_P4 762 M78076_PEA_1_T3 (SEQ ID
NO: 717)
M78076_PEA_1_P12 763 M78076_PEA_1_T13 (SEQ
ID NO: 719)
M78076_PEA_1_P14 764 M78076_PEA_1_T15 (SEQ
ID NO: 720)
M78076_PEA_1_P21 765 M78076_PEA_1_T23 (SEQ
ID NO: 721)
M78076_PEA_1_P24 766 M78076_PEA_1_T26 (SEQ
ID NO: 722)
M78076_PEA_1_P2 767 M78076_PEA_1_T27 (SEQ
ID NO: 723)
M78076_PEA_1_P25 768 M78076_PEA_1_T28 (SEQ
ID NO: 724)

These sequences are variants of the known protein Amyloid-like protein 1 precursor (SwissProt accession identifier APP1_HUMAN; known also according to the synonyms APLP; APLP-1), SEQ ID NO: 760, referred to herein as the previously known protein.

Protein Amyloid-like protein 1 precursor (SEQ ID NO:760) is known or believed to have the following function(s): May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding (By similarity). Couples to JIP signal transduction through C-terminal binding. May interact with cellular G-protein signaling pathways. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis (By similarity). The sequence for protein Amyloid-like protein 1 precursor (SEQ ID NO:760) is given at the end of the application, as “Amyloid-like protein 1 precursor (SEQ ID NO:760) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
48 A -> P

Protein Amyloid-like protein 1 precursor (SEQ ID NO:760) localization is believed to be Type I membrane protein. C-terminally processed in the Golgi complex.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: endocytosis; apoptosis; cell adhesion; neurogenesis; cell death, which are annotation(s) related to Biological Process; protein binding; heparin binding, which are annotation(s) related to Molecular Function; and basement membrane; coated pit; integral membrane protein, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

As noted above, cluster M78076 features 9 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Amyloid-like protein 1 precursor (SEQ ID NO:760). A description of each variant protein according to the present invention is now provided.

Variant protein M78076_PEA—1_P3 (SEQ ID NO:761) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T2 (SEQ ID NO:716). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P3 (SEQ ID NO:761) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P3 (SEQ ID NO:761), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKD corresponding to amino acids 1-517 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-517 of M78076_PEA—1_P3 (SEQ ID NO:761), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GE corresponding to amino acids 518-519 of M78076_PEA—1_P3 (SEQ ID NO:761), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M78076_PEA—1_P3 (SEQ ID NO:761) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P3 (SEQ ID NO:761) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No

The glycosylation sites of variant protein M78076_PEA—1_P3 (SEQ ID NO:761), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 6 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 6
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 yes 461
551 no

Variant protein M78076_PEA—1_P3 (SEQ ID NO:761) is encoded by the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T2 (SEQ ID NO:716) is shown in bold; this coding portion starts at position 142 and ends at position 1698. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P3 (SEQ ID NO:761) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
2146 G -> A Yes
2224 C -> T No
2362 C -> T Yes
2513 A -> G No
2656 C -> T Yes

Variant protein M78076_PEA—1_P4 (SEQ ID NO:762) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T3 (SEQ ID NO:717). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P4 (SEQ ID NO:762) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P4 (SEQ ID NO:762), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1-526 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-526 of M78076_PEA—1_P4 (SEQ ID NO:762), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECLTVNPSLQIPLNP (SEQ ID NO:958) corresponding to amino acids 527-541 of M78076_PEA—1_P4 (SEQ ID NO:762), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of M78076_PEA—1_P4 (SEQ ID NO:762), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECLTVNPSLQIPLNP (SEQ ID NO:958) in M78076_PEA—1_P4 (SEQ ID NO:762).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M78076_PEA—1_P4 (SEQ ID NO:762) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P4 (SEQ ID NO:762) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No

The glycosylation sites of variant protein M78076_PEA—1_P4 (SEQ ID NO:762), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 9 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 9
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 yes 461
551 no

Variant protein M78076_PEA—1_P4 (SEQ ID NO:762) is encoded by the following transcript(s): M78076_PEA—1_T3 (SEQ ID NO:717), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T3 (SEQ ID NO:717) is shown in bold; this coding portion starts at position 142 and ends at position 1764. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P4 (SEQ ID NO:762) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
1817 G -> A Yes
2362 G -> A Yes
2440 C -> T No
2578 C -> T Yes
2729 A -> G No
2872 C -> T Yes

Variant protein M78076_PEA—1_P12 (SEQ ID NO:763) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T13 (SEQ ID NO:719). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P12 (SEQ ID NO:763) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P12 (SEQ ID NO:763), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1-526 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-526 of M78076_PEA—1_P12 (SEQ ID NO:763), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO:959) corresponding to amino acids 527-544 of M78076_PEA—1_P12 (SEQ ID NO:763), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of M78076_PEA—1_P12 (SEQ ID NO:763), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO:959) in M78076_PEA—1_P12 (SEQ ID NO:763).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M78076_PEA—1_P12 (SEQ ID NO:763) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P12 (SEQ ID NO:763) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No

The glycosylation sites of variant protein M78076_PEA—1_P12 (SEQ ID NO:763), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 12
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 yes 461
551 no

Variant protein M78076_PEA—1_P12 (SEQ ID NO:763) is encoded by the following transcript(s): M78076_PEA—1_T13 (SEQ ID NO:719), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T13 (SEQ ID NO:719) is shown in bold; this coding portion starts at position 142 and ends at position 1773. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P12 (SEQ ID NO:763) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
1816 G -> A Yes
1894 C -> T No
2032 C -> T Yes
2183 A -> G No
2326 C -> T Yes

Variant protein M78076_PEA—1_P14 (SEQ ID NO:764) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T15 (SEQ ID NO:720). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P14 (SEQ ID NO:764) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P14 (SEQ ID NO:764), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGST EQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDEL corresponding to amino acids 1-570 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-570 of M78076_PEA—1_P14 (SEQ ID NO:764), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO:960) corresponding to amino acids 571-619 of M78076_PEA—1_P14 (SEQ ID NO:764), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of M78076_PEA—1_P14 (SEQ ID NO:764), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO:960)
in M78076_PEA_1_P14. (SEQ ID NO:764)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M78076_PEA—1_P14 (SEQ ID NO:764) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P14 (SEQ ID NO:764) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No

The glycosylation sites of variant protein M78076_PEA—1_P14 (SEQ ID NO:764), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 15 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 15
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 yes 461
551 yes 551

Variant protein M78076_PEA—1_P14 (SEQ ID NO:764) is encoded by the following transcript(s): M78076_PEA—1_T15 (SEQ ID NO:720), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T15 (SEQ ID NO:720) is shown in bold; this coding portion starts at position 142 and ends at position 1998. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P14 (SEQ ID NO:764) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
2008 G -> A Yes
2086 C -> T No
2224 C -> T Yes
2375 A -> G No
2518 C -> T Yes

Variant protein M78076_PEA—1_P21 (SEQ ID NO:765) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T23 (SEQ ID NO:721). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P21 (SEQ ID NO:765) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P21 (SEQ ID NO:765), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN E corresponding to amino acids 1-352 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-352 of M78076_PEA—1_P21 (SEQ ID NO:765), and a second amino acid sequence being at least 90% homologous to AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQ SLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMT LPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDELAPAGTGVSREA VSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYE NPTYRFLEERP corresponding to amino acids 406-650 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 353-597 of M78076_PEA—1_P21 (SEQ ID NO:765), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated chimeric polypeptide encoding for an edge portion of M78076_PEA—1_P21 (SEQ ID NO:765), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EA, having a structure as follows: a sequence starting from any of amino acid numbers 352-x to 352; and ending at any of amino acid numbers 353+((n-2)−x), in which x varies from 0 to n-2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

Variant protein M78076_PEA—1_P21 (SEQ ID NO:765) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P21 (SEQ ID NO:765) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes

The glycosylation sites of variant protein M78076_PEA—1_P21 (SEQ ID NO:765), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 18 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 18
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 yes 408
551 yes 498

Variant protein M78076_PEA—1_P21 (SEQ ID NO:765) is encoded by the following transcript(s): M78076_PEA—1_T23 (SEQ ID NO:721), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T23 (SEQ ID NO:721) is shown in bold; this coding portion starts at position 142 and ends at position 1932. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P21 (SEQ ID NO:765) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1239 G -> T Yes
1264 C -> T Yes
1728 G -> A Yes
1806 C -> T No
1944 C -> T Yes
2095 A -> G No
2238 C -> T Yes

Variant protein M78076_PEA—1_P24 (SEQ ID NO:766) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T26 (SEQ ID NO:722). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P24 (SEQ ID NO:766) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P24 (SEQ ID NO:766), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQI corresponding to amino acids 1-481 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-481 of M78076_PEA—1_P24 (SEQ ID NO:766), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RECLLPWLPLQISEGRS (SEQ ID NO:961) corresponding to amino acids 482-498 of M78076_PEA—1P24 (SEQ ID NO:766), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of M78076_PEA—1_P24 (SEQ ID NO:766), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RECLLPWLPLQISEGRS (SEQ ID NO:961) in M78076_PEA—1_P24 (SEQ ID NO:766).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M78076_PEA—1_P24 (SEQ ID NO:766) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P24 (SEQ ID NO:766) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No

The glycosylation sites of variant protein M78076_PEA—1_P24 (SEQ ID NO:766), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 21 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 21
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 yes 461
551 no

Variant protein M78076_PEA—1_P24 (SEQ ID NO:766) is encoded by the following transcript(s): M78076_PEA—1_T26 (SEQ ID NO:722), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T26 (SEQ ID NO:722) is shown in bold; this coding portion starts at position 142 and ends at position 1635. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P24 (SEQ ID NO:766) sequence provides support for the deduced sequence variant protein according to the present invention).

TABLE 22
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
2184 G -> A Yes

Variant protein M78076_PEA—1_P2 (SEQ ID NO:767) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T27 (SEQ ID NO:723). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P2 (SEQ ID NO:767) and APP1_HUMAN (SEQ ID NO:760):

1. An isolated chimeric polypeptide encoding for M78076_PEA—1_P2 (SEQ ID NO:767), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQV corresponding to amino acids 1-449 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-449 of M78076_PEA—1_P2 (SEQ ID NO:767), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT STSWVQAILLPQPLE (SEQ ID NO:962) corresponding to amino acids 450-588 of M78076_PEA—1_P2 (SEQ ID NO:767), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of M78076_PEA—1_P2 (SEQ ID NO:767), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT (SEQ ID NO:962)
CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT
STSWVQAILLPQPLE
in M78076_PEA_1_P2. (SEQ ID NO:767)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

Variant protein M78076_PEA—1_P2 (SEQ ID NO:767) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P2 (SEQ ID NO:767) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No
520 A -> S Yes
546 F -> Yes
564 S -> C Yes

The glycosylation sites of variant protein M78076_PEA—1_P2 (SEQ ID NO:767), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 24 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 24
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 no
551 no

Variant protein M78076_PEA—1_P2 (SEQ ID NO:767) is encoded by the following transcript(s): M78076_PEA—1_T27 (SEQ ID NO:723), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T27 (SEQ ID NO:723) is shown in bold; this coding portion starts at position 142 and ends at position 1905. The transcript also has the following SNPs as listed in Table 25 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P2 (SEQ ID NO:767) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
1500 C -> T Yes
1699 G -> T Yes
1725 G -> A Yes
1777 T -> Yes
1831 A -> T Yes
2274 A -> G Yes
2525 A -> G Yes
2681 G -> A Yes
3831 G -> A Yes

Variant protein M78076_PEA—1_P25 (SEQ ID NO:768) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78076_PEA—1_T28 (SEQ ID NO:724). An alignment is given to the known protein (Amyloid-like protein 1 precursor (SEQ ID NO:760)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between M78076_PEA—1_P25 (SEQ ID NO:768) and APP1_HUMAN (SEQ ID NO:760):

1.An isolated chimeric polypeptide encoding for M78076_PEA—1_P25 (SEQ ID NO:768), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQ corresponding to amino acids 1-448 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-448 of M78076_PEA—1_P25 (SEQ ID NO:768), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID NO:963) corresponding to amino acids 449-505 of M78076_PEA—1_P25 (SEQ ID NO:768), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated polypeptide encoding for a tail of M78076_PEA—1_P25 (SEQ ID NO:768), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID NO:963)
in M78076_PEA_1_P25. (SEQ ID NO:768)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M78076_PEA—1_P25 (SEQ ID NO:768) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 26, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P25 (SEQ ID NO:768) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26
Amino acid mutations
SNP position(s) on amino acid Alternative
sequence amino acid(s) Previously known SNP?
4 A -> P Yes
6 P -> H Yes
13 R -> H Yes
34 Q -> No
38 G -> R Yes
88 P -> R Yes
124 R -> Q Yes
127 S -> No
145 F -> S No
214 G -> R No
214 G -> No
262 Q -> No
270 V -> No
309 G -> E Yes
370 Q -> No

The glycosylation sites of variant protein M78076_PEA—1_P25 (SEQ ID NO:768), as compared to the known protein Amyloid-like protein 1 precursor (SEQ ID NO:760), are described in Table 27 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 27
Glycosylation site(s)
Position(s) on known amino Present in Position
acid sequence variant protein? in variant protein?
337 yes 337
461 no
551 no

Variant protein M78076_PEA—1_P25 (SEQ ID NO:768) is encoded by the following transcript(s): M78076_PEA—1_T28 (SEQ ID NO:724), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78076_PEA—1_T28 (SEQ ID NO:724) is shown in bold; this coding portion starts at position 142 and ends at position 1656. The transcript also has the following SNPs as listed in Table 28 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78076_PEA—1_P25 (SEQ ID NO:768) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 28
Nucleic acid SNPs
SNP position on nucleotide Alternative
sequence nucleic acid Previously known SNP?
114 G -> No
151 G -> C Yes
158 C -> A Yes
179 G -> A Yes
219 A -> G Yes
243 G -> No
253 G -> A Yes
315 A -> G Yes
366 A -> G Yes
404 C -> G Yes
512 G -> A Yes
522 C -> No
522 C -> T No
575 T -> C No
781 G -> No
781 G -> A No
927 G -> No
951 C -> No
1067 G -> A Yes
1077 G -> A Yes
1251 G -> No
1398 G -> T Yes
1423 C -> T Yes
1593 A -> G No
1736 C -> T Yes

As noted above, cluster M78076 features 35 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster M78076_PEA—1_node—0 (SEQ ID NO:725) according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1 160
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1 160
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1 160
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1 160
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1 160
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1 160
NO: 721)
M78076_PEA_1_T26 (SEQ ID 1 160
NO: 722)
M78076_PEA_1_T27 (SEQ ID 1 160
NO: 723)
M78076_PEA_1_T28 (SEQ ID 1 160
NO: 724)

Segment cluster M78076_PEA—1_node—10 (SEQ ID NO:726) according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 433 565
NO: 716)
M78076_PEA_1_T3 (SEQ ID 433 565
NO: 717)
M78076_PEA_1_T5 (SEQ ID 433 565
NO: 718)
M78076_PEA_1_T13 (SEQ ID 433 565
NO: 719)
M78076_PEA_1_T15 (SEQ ID 433 565
NO: 720)
M78076_PEA_1_T23 (SEQ ID 433 565
NO: 721)
M78076_PEA_1_T26 (SEQ ID 433 565
NO: 722)
M78076_PEA_1_T27 (SEQ ID 433 565
NO: 723)
M78076_PEA_1_T28 (SEQ ID 433 565
NO: 724)

Segment cluster M78076_PEA—1_node—15 (SEQ ID NO:727) according to the present invention is supported by 74 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 679 812
NO: 716)
M78076_PEA_1_T3 (SEQ ID 679 812
NO: 717)
M78076_PEA_1_T5 (SEQ ID 679 812
NO: 718)
M78076_PEA_1_T13 (SEQ ID 679 812
NO: 719)
M78076_PEA_1_T15 (SEQ ID 679 812
NO: 720)
M78076_PEA_1_T23 (SEQ ID 679 812
NO: 721)
M78076_PEA_1_T26 (SEQ ID 679 812
NO: 722)
M78076_PEA_1_T27 (SEQ ID 679 812
NO: 723)
M78076_PEA_1_T28 (SEQ ID 679 812
NO: 724)

Segment cluster M78076_PEA—1_node—18 (SEQ ID NO:728) according to the present invention is supported by 95 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 813 991
NO: 716)
M78076_PEA_1_T3 (SEQ ID 813 991
NO: 717)
M78076_PEA_1_T5 (SEQ ID 813 991
NO: 718)
M78076_PEA_1_T13 (SEQ ID 813 991
NO: 719)
M78076_PEA_1_T15 (SEQ ID 813 991
NO: 720)
M78076_PEA_1_T23 (SEQ ID 813 991
NO: 721)
M78076_PEA_1_T26 (SEQ ID 813 991
NO: 722)
M78076_PEA_1_T27 (SEQ ID 813 991
NO: 723)
M78076_PEA_1_T28 (SEQ ID 813 991
NO: 724)

Segment cluster M78076_PEA—1_node—20 (SEQ ID NO:729) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 992 1122
NO: 716)
M78076_PEA_1_T3 (SEQ ID 992 1122
NO: 717)
M78076_PEA_1_T5 (SEQ ID 992 1122
NO: 718)
M78076_PEA_1_T13 (SEQ ID 992 1122
NO: 719)
M78076_PEA_1_T15 (SEQ ID 992 1122
NO: 720)
M78076_PEA_1_T23 (SEQ ID 992 1122
NO: 721)
M78076_PEA_1_T26 (SEQ ID 992 1122
NO: 722)
M78076_PEA_1_T27 (SEQ ID 992 1122
NO: 723)
M78076_PEA_1_T28 (SEQ ID 992 1122
NO: 724)

Segment cluster M78076_PEA—1_node—24 (SEQ ID NO:730) according to the present invention is supported by 105 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1198 1356
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1198 1356
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1198 1356
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1198 1356
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1198 1356
NO: 720)
M78076_PEA_1_T26 (SEQ ID 1198 1356
NO: 722)
M78076_PEA_1_T27 (SEQ ID 1198 1356
NO: 723)
M78076_PEA_1_T28 (SEQ ID 1198 1356
NO: 724)

Segment cluster M78076_PEA—1_node—26 (SEQ ID NO:731) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1357 1485
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1357 1485
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1357 1485
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1357 1485
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1357 1485
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1198 1326
NO: 721)
M78076_PEA_1_T26 (SEQ ID 1357 1485
NO: 722)
M78076_PEA_1_T27 (SEQ ID 1357 1485
NO: 723)
M78076_PEA_1_T28 (SEQ ID 1357 1485
NO: 724)

Segment cluster M78076_PEA—1_node—29 (SEQ ID NO:732) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T27 (SEQ ID NO:723). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T27 (SEQ ID 1490 3132
NO: 723)

Segment cluster M78076_PEA—1_node—32 (SEQ ID NO:733) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T26 (SEQ ID NO:722) and M78076_PEA—1T27 (SEQ ID NO:723). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T26 (SEQ ID 1586 2457
NO: 722)
M78076_PEA_1_T27 (SEQ ID 3233 4104
NO: 723)

Segment cluster M78076 PEA—1_node—35 (SEQ ID NO:734) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716) and M78076_PEA—1_T5 (SEQ ID NO:718). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1694 1952
NO: 716)
M78076_PEA_1_T5 (SEQ ID 1694 1952
NO: 718)

Segment cluster M78076_PEA—1_node—37 (SEQ ID NO:735) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T3 (SEQ ID NO:717) and M78076_PEA—1_T5 (SEQ ID NO:718). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T3 (SEQ ID 1718 2180
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1977 2439
NO: 718)

Segment cluster M78076_PEA—1_node—46 (SEQ ID NO:736) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T15 (SEQ ID NO:720). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T15 (SEQ ID 1852 1972
NO: 720)

Segment cluster M78076_PEA—1_node—47 (SEQ ID NO:737) according to the present invention is supported by 155 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718) M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2111 2254
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2327 2470
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2586 2729
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1781 1924
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1973 2116
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1693 1836
NO: 721)

Segment cluster M78076_PEA—1_node—54 (SEQ ID NO:738) according to the present invention is supported by 133 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2412 2715
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2628 2931
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2887 3190
NO: 718)
M78076_PEA_1_T13 (SEQ ID 2082 2385
NO: 719)
M78076_PEA_1_T15 (SEQ ID 2274 2577
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1994 2297
NO: 721)
M78076_PEA_1_T28 (SEQ ID 1492 1795
NO: 724)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster M78076_PEA—1_node—1 (SEQ ID NO:739) according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 161 204
NO: 716)
M78076_PEA_1_T3 (SEQ ID 161 204
NO: 717)
M78076_PEA_1_T5 (SEQ ID 161 204
NO: 718)
M78076_PEA_1_T13 (SEQ ID 161 204
NO: 719)
M78076_PEA_1_T15 (SEQ ID 161 204
NO: 720)
M78076_PEA_1_T23 (SEQ ID 161 204
NO: 721)
M78076_PEA_1_T26 (SEQ ID 161 204
NO: 722)
M78076_PEA_1_T27 (SEQ ID 161 204
NO: 723)
M78076_PEA_1_T28 (SEQ ID 161 204
NO: 724)

Segment cluster M78076_PEA—1_node—2 (SEQ ID NO:740) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 205 224
NO: 716)
M78076_PEA_1_T3 (SEQ ID 205 224
NO: 717)
M78076_PEA_1_T5 (SEQ ID 205 224
NO: 718)
M78076_PEA_1_T13 (SEQ ID 205 224
NO: 719)
M78076_PEA_1_T15 (SEQ ID 205 224
NO: 720)
M78076_PEA_1_T23 (SEQ ID 205 224
NO: 721)
M78076_PEA_1_T26 (SEQ ID 205 224
NO: 722)
M78076_PEA_1_T27 (SEQ ID 205 224
NO: 723)
M78076_PEA_1_T28 (SEQ ID 205 224
NO: 724)

Segment cluster M78076_PEA—1node—3 (SEQ ID NO:741) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718) M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 225 288
NO: 716)
M78076_PEA_1_T3 (SEQ ID 225 288
NO: 717)
M78076_PEA_1_T5 (SEQ ID 225 288
NO: 718)
M78076_PEA_1_T13 (SEQ ID 225 288
NO: 719)
M78076_PEA_1_T15 (SEQ ID 225 288
NO: 720)
M78076_PEA_1_T23 (SEQ ID 225 288
NO: 721)
M78076_PEA_1_T26 (SEQ ID 225 288
NO: 722)
M78076_PEA_1_T27 (SEQ ID 225 288
NO: 723)
M78076_PEA_1_T28 (SEQ ID 225 288
NO: 724)

Segment cluster M78076_PEA—1_node—6 (SEQ ID NO:742) according to the present invention is supported by 59 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 289 370
NO: 716)
M78076_PEA_1_T3 (SEQ ID 289 370
NO: 717)
M78076_PEA_1_T5 (SEQ ID 289 370
NO: 718)
M78076_PEA_1_T13 (SEQ ID 289 370
NO: 719)
M78076_PEA_1_T15 (SEQ ID 289 370
NO: 720)
M78076_PEA_1_T23 (SEQ ID 289 370
NO: 721)
M78076_PEA_1_T26 (SEQ ID 289 370
NO: 722)
M78076_PEA_1_T27 (SEQ ID 289 370
NO: 723)
M78076_PEA_1_T28 (SEQ ID 289 370
NO: 724)

Segment cluster M78076_PEA—1_node—7 (SEQ ID NO:743) according to the present invention is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 371 432
NO: 716)
M78076_PEA_1_T3 (SEQ ID 371 432
NO: 717)
M78076_PEA_1_T5 (SEQ ID 371 432
NO: 718)
M78076_PEA_1_T13 (SEQ ID 371 432
NO: 719)
M78076_PEA_1_T15 (SEQ ID 371 432
NO: 720)
M78076_PEA_1_T23 (SEQ ID 371 432
NO: 721)
M78076_PEA_1_T26 (SEQ ID 371 432
NO: 722)
M78076_PEA_1_T27 (SEQ ID 371 432
NO: 723)
M78076_PEA_1_T28 (SEQ ID 371 432
NO: 724)

Segment cluster M78076_PEA—1_node—12 (SEQ ID NO:744) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 566 678
NO: 716)
M78076_PEA_1_T3 (SEQ ID 566 678
NO: 717)
M78076_PEA_1_T5 (SEQ ID 566 678
NO: 718)
M78076_PEA_1_T13 (SEQ ID 566 678
NO: 719)
M78076_PEA_1_T15 (SEQ ID 566 678
NO: 720)
M78076_PEA_1_T23 (SEQ ID 566 678
NO: 721)
M78076_PEA_1_T26 (SEQ ID 566 678
NO: 722)
M78076_PEA_1_T27 (SEQ ID 566 678
NO: 723)
M78076_PEA_1_T28 (SEQ ID 566 678
NO: 724)

Segment cluster M78076_PEA—1_node—22 (SEQ ID NO:745) according to the present invention is supported by 92 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722), M78076_PEA—1_T27 (SEQ ID NO:723) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1123 1197
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1123 1197
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1123 1197
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1123 1197
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1123 1197
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1123 1197
NO: 721)
M78076_PEA_1_T26 (SEQ ID 1123 1197
NO: 722)
M78076_PEA_1_T27 (SEQ ID 1123 1197
NO: 723)
M78076_PEA_1_T28 (SEQ ID 1123 1197
NO: 724)

Segment cluster M78076_PEA—1_node—27 (SEQ ID NO:746) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T27 (SEQ ID NO:723). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T27 (SEQ ID 1486 1489
NO: 723)

Segment cluster M78076_PEA—1_node—30 (SEQ ID NO:747) according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722) and M78076_PEA—1_T27 (SEQ ID NO:723). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1486 1557
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1486 1557
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1486 1557
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1486 1557
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1486 1557
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1327 1398
NO: 721)
M78076_PEA_1_T26 (SEQ ID 1486 1557
NO: 722)
M78076_PEA_1_T27 (SEQ ID 3133 3204
NO: 723)

Segment cluster M78076_PEA—1_node—31 (SEQ ID NO:748) according to the present invention is supported by 89 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721), M78076_PEA—1_T26 (SEQ ID NO:722) and M78076_PEA—1_T27 (SEQ ID NO:723). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1558 1585
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1558 1585
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1558 1585
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1558 1585
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1558 1585
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1399 1426
NO: 721)
M78076_PEA_1_T26 (SEQ ID 1558 1585
NO: 722)
M78076_PEA_1_T27 (SEQ ID 3205 3232
NO: 723)

Segment cluster M78076_PEA—1_node—34 (SEQ ID NO:749) according to the present invention is supported by 103 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1586 1693
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1586 1693
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1586 1693
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1586 1693
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1586 1693
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1427 1534
NO: 721)

Segment cluster M78076_PEA—1_node—36 (SEQ ID NO:750) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1953 1976
NO: 716)
M78076_PEA_1_T3 (SEQ ID 1694 1717
NO: 717)
M78076_PEA_1_T5 (SEQ ID 1953 1976
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1694 1717
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1694 1717
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1535 1558
NO: 721)

Segment cluster M78076_PEA—1_node—41 (SEQ ID NO:751) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T3 (SEQ ID NO:717) and M78076_PEA—1_T5 (SEQ ID NO:718). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T3 (SEQ ID 2181 2192
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2440 2451
NO: 718)

Segment cluster M78076_PEA—1_node—42 (SEQ ID NO:752) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1977 1985
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2193 2201
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2452 2460
NO: 718)
M78076_PEA_1_T15 (SEQ ID 1718 1726
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1559 1567
NO: 721)

Segment cluster M78076_PEA—1_node—43 (SEQ ID NO:753) according to the present invention is supported by 110 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 1986 2047
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2202 2263
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2461 2522
NO: 718)
M78076_PEA_1_T15 (SEQ ID 1727 1788
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1568 1629
NO: 721)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 58.

TABLE 58
Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
M78076_0_7_0 (SEQ ID breast malignant tumors BRS
NO: 914)

Segment cluster M78076_PEA—1_node—45 (SEQ ID NO:754) according to the present invention is supported by 132 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2048 2110
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2264 2326
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2523 2585
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1718 1780
NO: 719)
M78076_PEA_1_T15 (SEQ ID 1789 1851
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1630 1692
NO: 721)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 60.

TABLE 60
Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
M78076_0_7_0 (SEQ ID breast malignant tumors BRS
NO: 914)

Segment cluster M78076_PEA—1_node—49 (SEQ ID NO:755) according to the present invention is supported by 129 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2255 2290
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2471 2506
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2730 2765
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1925 1960
NO: 719)
M78076_PEA_1_T15 (SEQ ID 2117 2152
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1837 1872
NO: 721)

Segment cluster M78076_PEA—1_node—50 (SEQ ID NO:756) according to the present invention is supported by 125 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2291 2329
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2507 2545
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2766 2804
NO: 718)
M78076_PEA_1_T13 (SEQ ID 1961 1999
NO: 719)
M78076_PEA_1_T15 (SEQ ID 2153 2191
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1873 1911
NO: 721)

Segment cluster M78076_PEA—1_node—51 (SEQ ID NO:757) according to the present invention is supported by 123 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2330 2388
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2546 2604
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2805 2863
NO: 718)
M78076_PEA_1_T13 (SEQ ID 2000 2058
NO: 719)
M78076_PEA_1_T15 (SEQ ID 2192 2250
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1912 1970
NO: 721)

Segment cluster M78076_PEA—1_node—52 (SEQ ID NO:758) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720) and M78076_PEA—1_T23 (SEQ ID NO:721). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2389 2405
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2605 2621
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2864 2880
NO: 718)
M78076_PEA_1_T13 (SEQ ID 2059 2075
NO: 719)
M78076_PEA_1_T15 (SEQ ID 2251 2267
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1971 1987
NO: 721)

Segment cluster M78076_PEA—1_node—53 (SEQ ID NO:759) according to the present invention can be found in the following transcript(s): M78076_PEA—1_T2 (SEQ ID NO:716), M78076_PEA—1_T3 (SEQ ID NO:717), M78076_PEA—1_T5 (SEQ ID NO:718), M78076_PEA—1_T13 (SEQ ID NO:719), M78076_PEA—1_T15 (SEQ ID NO:720), M78076_PEA—1_T23 (SEQ ID NO:721) and M78076_PEA—1_T28 (SEQ ID NO:724). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65
Segment location on transcripts
Segment Segment
Transcript name starting position ending position
M78076_PEA_1_T2 (SEQ ID 2406 2411
NO: 716)
M78076_PEA_1_T3 (SEQ ID 2622 2627
NO: 717)
M78076_PEA_1_T5 (SEQ ID 2881 2886
NO: 718)
M78076_PEA_1_T13 (SEQ ID 2076 2081
NO: 719)
M78076_PEA_1_T15 (SEQ ID 2268 2273
NO: 720)
M78076_PEA_1_T23 (SEQ ID 1988 1993
NO: 721)
M78076_PEA_1_T28 (SEQ ID 1486 1491
NO: 724)

Variant protein alignment to the previously known protein:

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1_P3 (SEQ ID NO:761)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 5132.00

Quality: 5132.00
Escore: 0
Matching length: 517 Total length: 517
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
         ·         ·         ·         ·         ·
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
         ·
501 GGSSEDKGGLQPPDSKD 517
|||||||||||||||||
501 GGSSEDKGGLQPPDSKD 517

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1_P4 (SEQ ID NO:762)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 5223.00
Escore: 0
Matching length: 526 Total length: 526
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRRTLRHYQHVAAVDPEKAQQMRFQVH 450
         ·         ·         ·         ·         ·
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
         ·         ·
501 GGSSEDKGGLQPPDSKDDTPMTLPKG 526
||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSKDDTPMTLPKG 526

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1P12 (SEQ ID NO:763)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 5223.00
Escore: 0
Matching length: 526 Total length: 526
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
         ·         ·         ·         ·         ·
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
         ·         ·
501 GGSSEDKGGLQPPDSKDDTPMTLPKG 526
||||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSKDDTPMTLPKG 526

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1P14 (SEQ ID NO:764)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 5672.00
Escore: 0
Matching length: 575 Total length: 575
Matching Percent 99.48 Matching Percent Identity: 99.48
Similarity:
Total Percent Similarity: 99.48 Total Percent Identity: 99.48
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
         ·         ·         ·         ·         ·
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
||||||||||||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
         ·         ·         ·         ·         ·
501 GGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKV 550
||||||||||||||||||||||||||||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKV 550
         ·         ·
551 NASVPRGFPFHSSEIQRDELVRGGT 575
||||||||||||||||||||   ||
551 NASVPRGFPFHSSEIQRDELAPAGT 575

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1_P21 (SEQ ID NO:765)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 5822.00
Escore: 0
Matching length: 597 Total length: 650
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 91.85 Total Percent Identity: 91.85
Gaps: 1

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NE................................................ 352
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
353 .....AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 397
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
         ·         ·         ·         ·         ·
398 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 447
||||||||||||||||||||||||||||||||||||||||||||||||||
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAP 500
         ·         ·         ·         ·         ·
448 GGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYEPKV 497
||||||||||||||||||||||||||||||||||||||||||||||||||
501 GGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKV 550
         ·         ·         ·         ·         ·
498 NASVPRGFPFHSSEIQRDELAPAGTGVSREAVSGLLIMGAGGGSLIVLSM 547
||||||||||||||||||||||||||||||||||||||||||||||||||
551 NASVPRGFPFHSSEIQRDELAPAGTGVSREAVSGLLIMGAGGGSLIVLSM 600
         ·         ·         ·         ·         ·
548 LLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP 597
||||||||||||||||||||||||||||||||||||||||||||||||||
601 LLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP 650

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1_P24 (SEQ ID NO:766)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 4791.00
Escore: 0
Matching length: 485 Total length: 485
Matching Percent 99.79 Matching Percent Identity: 99.59
Similarity:
Total Percent Similarity: 99.79 Total Percent Identity: 99.59
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGETSEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGETSEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
         ·         ·         ·
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIRECL 485
|||||||||||||||||||||||||||||||:| |
451 THLQVIEERVNQSLGLLDQNPHLAQELRPQIQELL 485

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1_P2 (SEQ ID NO:767)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 4474.00
Escore: 0
Matching length: 454 Total length: 454
Matching Percent 99.56 Matching Percent Identity: 99.34
Similarity:
Total Percent Similarity: 99.56 Total Percent Identity: 99.34
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDIYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVL 450
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVH 450
451 TSFQ 454
| :|
451 THLQ 454

Sequence name: APP1_HUMAN (SEQ ID NO:760)

Sequence documentation:

Alignment of: M78076_PEA—1_P25 (SEQ ID NO:768)×APP1_HUMAN (SEQ ID NO:760).

Alignment segment 1/1:

Quality: 4455.00
Escore: 0
Matching length: 448 Total length: 448
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 100.00 Total Percent Identity: 100.00
Gaps: 0

Alignment:

         ·         ·         ·         ·         ·
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEA 50
         ·         ·         ·         ·         ·
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
||||||||||||||||||||||||||||||||||||||||||||||||||
51 PGSAQVAGLCGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYP 100
         ·         ·         ·         ·         ·
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
||||||||||||||||||||||||||||||||||||||||||||||||||
101 ELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEAL 150
         ·         ·         ·         ·         ·
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
||||||||||||||||||||||||||||||||||||||||||||||||||
151 LVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSD 200
         ·         ·         ·         ·         ·
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
||||||||||||||||||||||||||||||||||||||||||||||||||
201 RFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFP 250
         ·         ·         ·         ·         ·
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDTYFGM 300
||||||||||||||||||||||||||||||||||||||||||||||||||
251 QPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGVDTYFGM 300
         ·         ·         ·         ·         ·
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
||||||||||||||||||||||||||||||||||||||||||||||||||
301 PGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQAL 350
         ·         ·         ·         ·         ·
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
||||||||||||||||||||||||||||||||||||||||||||||||||
351 NEHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQ 400
         ·         ·         ·         ·
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQ 448
||||||||||||||||||||||||||||||||||||||||||||||||||
401 ADPPQAERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQ 448

Description for Cluster HSMUC1A

Cluster HSMUC1A features 14 transcript(s) and 22 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HSMUC1A_PEA_1_T12 769
HSMUC1A_PEA_1_T26 770
HSMUC1A_PEA_1_T28 771
HSMUC1A_PEA_1_T29 772
HSMUC1A_PEA_1_T30 773
HSMUC1A_PEA_1_T31 774
HSMUC1A_PEA_1_T33 775
HSMUC1A_PEA_1_T34 776
HSMUC1A_PEA_1_T35 777
HSMUC1A_PEA_1_T36 778
HSMUC1A_PEA_1_T40 779
HSMUC1A_PEA_1_T42 780
HSMUC1A_PEA_1_T43 781
HSMUC1A_PEA_1_T47 782

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HSMUC1A_PEA_1_node_0 783
HSMUC1A_PEA_1_node_14 784
HSMUC1A_PEA_1_node_24 785
HSMUC1A_PEA_1_node_29 786
HSMUC1A_PEA_1_node_35 787
HSMUC1A_PEA_1_node_38 788
HSMUC1A_PEA_1_node_3 789
HSMUC1A_PEA_1_node_4 790
HSMUC1A_PEA_1_node_5 791
HSMUC1A_PEA_1_node_6 792
HSMUC1A_PEA_1_node_7 793
HSMUC1A_PEA_1_node_17 794
HSMUC1A_PEA_1_node_18 795
HSMUC1A_PEA_1_node_20 796
HSMUC1A_PEA_1_node_21 797
HSMUC1A_PEA_1_node_23 798
HSMUC1A_PEA_1_node_26 799
HSMUC1A_PEA_1_node_27 800
HSMUC1A_PEA_1_node_31 801
HSMUC1A_PEA_1_node_34 802
HSMUC1A_PEA_1_node_36 803
HSMUC1A_PEA_1_node_37 804

TABLE 3
Proteins of interest
Sequence ID Corresponding
Protein Name No. Transcript(s)
HSMUC1A_PEA_1_P25 806 HSMUC1A_PEA_1_T26
(SEQ ID NO:770)
HSMUC1A_PEA_1_P29 807 HSMUC1A_PEA_1_T33
(SEQ ID NO:775)
HSMUC1A_PEA_1_P30 808 HSMUC1A_PEA_1_T34
(SEQ ID NO:776)
HSMUC1A_PEA_1_P32 809 HSMUC1A_PEA_1_T36
(SEQ ID NO:778)
HSMUC1A_PEA_1_P36 810 HSMUC1A_PEA_1_T40
(SEQ ID NO:779)
HSMUC1A_PEA_1_P39 811 HSMUC1A_PEA_1_T43
(SEQ ID NO:781)
HSMUC1A_PEA_1_P45 812 HSMUC1A_PEA_1_T29
(SEQ ID NO:772)
HSMUC1A_PEA_1_P49 813 HSMUC1A_PEA_1_T12
(SEQ ID NO:813) (SEQ ID NO:769)
HSMUC1A_PEA_1_P52 814 HSMUC1A_PEA_1_T30
(SEQ ID NO:773)
HSMUC1A_PEA_1_P53 815 HSMUC1A_PEA_1_T31
(SEQ ID NO:774)
HSMUC1A_PEA_1_P56 816 HSMUC1A_PEA_1_T42
(SEQ ID NO:780)
HSMUC1A_PEA_1_P58 817 HSMUC1A_PEA_1_T35
(SEQ ID NO:777)
HSMUC1A_PEA_1_P59 818 HSMUC1A_PEA_1_T28
(SEQ ID NO:771)
HSMUC1A_PEA_1_P63 819 HSMUC1A_PEA_1_T47
(SEQ ID NO:782)

These sequences are variants of the known protein Mucin 1 precursor (SwissProt accession identifier MUC1_HUMAN; known also according to the synonyms MUC-1; Polymorphic epithelial mucin; PEM; PEMT; Episialin; Tumor-associated mucin; Carcinoma-associated mucin; Tumor-associated epithelial membrane antigen; EMA; H23AG; Peanut-reactive urinary mucin; PUM; Breast carcinoma-associated antigen DF3; CD227 antigen), SEQ ID NO: 805, referred to herein as the previously known protein.

Protein Mucin 1 precursor (SEQ ID NO:805) is known or believed to have the following function(s): May play a role in adhesive functions and in cell-cell interactions, metastasis and signaling. May provide a protective layer on epithelial surfaces. Direct or indirect interaction with actin cytoskeleton. Isoform 7 behaves as a receptor and binds the secreted isoform 5. The binding induces the phosphorylation of the isoform 7, alters cellular morphology and initiates cell signaling. Can bind to GRB2 adapter protein. The sequence for protein Mucin 1 precursor (SEQ ID NO:805) is given at the end of the application, as “Mucin 1 precursor (SEQ ID NO:805) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4
Amino acid mutations for Known Protein
SNP position(s) on
amino acid sequence Comment
1116 D->E: NO EFFECT ON BINDING OF
ISOFORM 7.
1116 D->A: DRASTICALLY REDUCED BINDING OF
ISOFORM 7.
2 T -> A
134 P -> Q
154 P -> Q
1021 S -> T
1117 V -> M
1193 Q -> L
1231 K -> T
1251 A -> T

Protein Mucin 1 precursor (SEQ ID NO:805) localization is believed to be Type I membrane protein. Two secreted forms (5 and 9) are also produced.

The previously known protein also has the following indication(s) and/or potential thereaputic use(s): Cancer, breast; Cancer, lung, non-small cell; Cancer, ovarian; Cancer, prostate. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: CD8 agonist; DNA antagonist; Immunostimulant; Interferon gamma agonist; MUC-1 inhibitor. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anticancer; Monoclonal antibody, murine; Immunotoxin; Immunostimulant; Immunoconjugate.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: actin binding, which are annotation(s) related to Molecular Function; and cytoskeleton; integral plasma membrane protein, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HSMUC1A can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 43 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 43 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

TABLE 5
Normal tissue distribution
Name of Tissue Number
bladder 41
brain 2
colon 66
epithelial 96
general 36
head and neck 314
kidney 282
lung 200
breast 61
ovary 0
pancreas 12
prostate 24
stomach 296
Thyroid 0
uterus 122

TABLE 6
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
bladder 3.3e−01 4.5e−01 1.8e−02 2.4 8.9e−02 1.7
brain 3.0e−02 2.6e−02 1.2e−01 4.6 1.1e−01 3.9
colon 1.2e−01 2.4e−01 3.8e−01 1.6 5.9e−01 1.2
epithelial 5.4e−02 6.0e−01 7.3e−06 1.8 6.2e−02 1.1
general 6.5e−07 2.6e−03 4.0e−23 3.6 1.7e−12 2.3
head and neck 6.4e−01 7.2e−01 1 0.3 1 0.3
kidney 7.8e−01 8.1e−01 1 0.3 1 0.2
lung 7.6e−01 7.9e−01 6.7e−01 0.8 1 0.4
breast 8.2e−02 1.3e−01 4.1e−03 3.6 7.7e−02 2.0
ovary 3.0e−02 4.3e−02 6.9e−02 4.4 1.6e−01 3.2
pancreas 7.2e−02 1.4e−01 9.6e−07 5.4 1.5e−05 4.5
prostate 7.0e−01 6.0e−01 1.5e−02 1.4 6.9e−04 3.2
stomach 3.1e−01 7.1e−01 1.5e−01 0.4 4.6e−01 0.8
Thyroid 2.9e−01 2.9e−01 4.4e−01 2.0 4.4e−01 2.0
uterus 2.4e−01 6.5e−01 1.6e−01 1.0 7.0e−01 0.6

For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously described. The following oligonucleotides were found to hit this cluster but not other segments/transcripts below (in relation to breast cancer), shown in Table 7.

TABLE 7
Oligonucleotides related to this cluster
Oligonucleotide Overexpressed in Chip
name cancers reference
HSMUC1A_0_0_11364 breast malignant BRS
(SEQ ID NO:916) tumors

As noted above, cluster HSMUC1A features 14 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Mucin 1 precursor (SEQ ID NO:805). A description of each variant protein according to the present invention is now provided.

Variant protein HSMUC1A_PEA—1_P25 (SEQ ID NO:806) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T26 (SEQ ID NO:770). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide.

Variant protein HSMUC1A_PEA—1_P25 (SEQ ID NO:806) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P25 (SEQ ID NO:806) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
90 S -> N Yes
91 D -> N No
157 Y -> No
187 S -> G No

Variant protein HSMUC1A_PEA—1_P25 (SEQ ID NO:806) is encoded by the following transcript(s): HSMUC1A_PEA—1_T26 (SEQ ID NO:770), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T26 (SEQ ID NO:770) is shown in bold; this coding portion starts at position 507 and ends at position 1115. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P25 (SEQ ID NO:806) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
775 G -> A Yes
777 G -> A No
977 C -> No
1065 A -> G No
1073 C -> T No
1079 C -> T Yes
1124 C -> T Yes
1177 C -> T No
1197 C -> T Yes
1303 G -> No
1315 G -> A Yes
1316 C -> No
1316 C -> T No
1405 A -> T No

Variant protein HSMUC1A_PEA—1_P29 (SEQ ID NO:807) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T33 (SEQ ID NO:775). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P29 (SEQ ID NO:807) is encoded by the following transcript(s): HSMUC1A_PEA—1_T33 (SEQ ID NO:775), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T33 (SEQ ID NO:775) is shown in bold; this coding portion starts at position 507 and ends at position 953. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P29 (SEQ ID NO:807) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
964 C -> No
1052 A -> G No
1060 C -> T No
1066 C -> T Yes
1111 C -> T Yes
1164 C -> T No
1184 C -> T Yes
1290 G -> No
1302 G -> A Yes
1303 C -> No
1303 C -> T No
1392 A -> T No

Variant protein HSMUC1A_PEA—1_P30 (SEQ ID NO:808) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T34 (SEQ ID NO:776). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide.

Variant protein HSMUC1A_PEA—1_P30 (SEQ ID NO:808) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P30 (SEQ ID NO:808) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
120 Y -> No
150 S -> G No

Variant protein HSMUC1A_PEA—1_P30 (SEQ ID NO:808) is encoded by the following transcript(s): HSMUC1A_PEA—1_T34 (SEQ ID NO:776), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T34 (SEQ ID NO:776) is shown in bold; this coding portion starts at position 507 and ends at position 1004. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P30 (SEQ ID NO:808) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
599 A -> G No
866 C -> No
954 A -> G No
962 C -> T No
968 C -> T Yes
1013 C -> T Yes
1066 C -> T No
1086 C -> T Yes
1192 G -> No
1204 G -> A Yes
1205 C -> No
1205 C -> T No
1294 A -> T No

Variant protein HSMUC1A_PEA—1_P32 (SEQ ID NO:809) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T36 (SEQ ID NO:778). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide.

Variant protein HSMUC1A_PEA—1_P32 (SEQ ID NO:809) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P32 (SEQ ID NO:809) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
111 Y -> No
141 S -> G No

Variant protein HSMUC1A_PEA—1_P32 (SEQ ID NO:809) is encoded by the following transcript(s): HSMUC1A_PEA—1_T36 (SEQ ID NO:778), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T36 (SEQ ID NO:778) is shown in bold; this coding portion starts at position 507 and ends at position 977. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P32 (SEQ ID NO:809) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
839 C -> No
927 A -> G No
935 C -> T No
941 C -> T Yes
986 C -> T Yes
1039 C -> T No
1059 C -> T Yes
1165 G -> No
1177 G -> A Yes
1178 C -> No
1178 C -> T No
1267 A -> T No

Variant protein HSMUC1A_PEA—1_P36 (SEQ ID NO:810) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T40 (SEQ ID NO:779). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P36 (SEQ ID NO:810) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P36 (SEQ ID NO:810) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
113 Y -> No
143 S -> G No

Variant protein HSMUC1A_PEA—1_P36 (SEQ ID NO:810) is encoded by the following transcript(s): HSMUC1A_PEA—1_T40 (SEQ ID NO:779), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T40 (SEQ ID NO:779) is shown in bold; this coding portion starts at position 507 and ends at position 983. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P36 (SEQ ID NO:810) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
599 A -> G No
845 C -> No
933 A -> G No
941 C -> T No
947 C -> T Yes
992 C -> T Yes
1045 C -> T No
1065 C -> T Yes
1171 G -> No
1183 G -> A Yes
1184 C -> No
1184 C -> T No
1273 A -> T No

Variant protein HSMUC1A_PEA—1_P39 (SEQ ID NO:811) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T43 (SEQ ID NO:781). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P39 (SEQ ID NO:811) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P39 (SEQ ID NO:811) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
90 Y -> No
120 S -> G No

Variant protein HSMUC1A_PEA—1_P39 (SEQ ID NO:811) is encoded by the following transcript(s): HSMUC1A_PEA—1_T43 (SEQ ID NO:781), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T43 (SEQ ID NO:781) is shown in bold; this coding portion starts at position 507 and ends at position 914. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P39 (SEQ ID NO:811) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
599 A -> G No
776 C -> No
864 A -> G No
872 C -> T No
878 C -> T Yes
923 C -> T Yes
976 C -> T No
996 C -> T Yes
1102 G -> No
1114 G -> A Yes
1115 C -> No
1115 C -> T No
1204 A -> T No

Variant protein HSMUC1A_PEA—1_P45 (SEQ ID NO:812) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T29 (SEQ ID NO:772). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P45 (SEQ ID NO:812) is encoded by the following transcript(s): HSMUC1A_PEA—1_T29 (SEQ ID NO:772), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T29 (SEQ ID NO:772) is shown in bold; this coding portion starts at position 507 and ends at position 746. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P45 (SEQ ID NO:812) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
599 A -> G No
746 G -> A Yes
748 G -> A No
948 C -> No
1036 A -> G No
1044 C -> T No
1050 C -> T Yes
1095 C -> T Yes
1148 C -> T No
1168 C -> T Yes
1274 G -> No
1286 G -> A Yes
1287 C -> No
1287 C -> T No
1376 A -> T No

Variant protein HSMUC1A_PEA—1_P49 (SEQ ID NO:813) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T12 (SEQ ID NO:769). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P49 (SEQ ID NO:813) is encoded by the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T12 (SEQ ID NO:769) is shown in bold; this coding portion starts at position 507 and ends at position 884. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P49 (SEQ ID NO:813) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
704 G -> A Yes
1012 G -> A Yes
1088 G -> A Yes
1090 G -> A No
1290 C -> No
1378 A -> G No
1386 C -> T No
1392 C -> T Yes
1437 C -> T Yes
1490 C -> T No
1510 C -> T Yes
1616 G -> No
1628 G -> A Yes
1629 C -> No
1629 C -> T No
1718 A -> T No

Variant protein HSMUC1A_PEA—1_P52 (SEQ ID NO:814) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T30 (SEQ ID NO:773). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to was secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P52 (SEQ ID NO:814) is encoded by the following transcript(s): HSMUC1A_PEA—1_T30 (SEQ ID NO:773), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T30 (SEQ ID NO:773) is shown in bold; this coding portion starts at position 507 and ends at position 719. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P52 (SEQ ID NO:814) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
719 G -> A Yes
721 G -> A No
921 C -> No
1009 A -> G No
1017 C -> T No
1023 C -> T Yes
1068 C -> T Yes
1121 C -> T No
1141 C -> T Yes
1247 G -> No
1259 G -> A Yes
1260 C -> No
1260 C -> T No
1349 A -> T No

Variant protein HSMUC1A_PEA—1_P53 (SEQ ID NO:815) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T31 (SEQ ID NO:774). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P53 (SEQ ID NO:815) is encoded by the following transcript(s): HSMUC1A_PEA—1_T31 (SEQ ID NO:774), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T31 (SEQ ID NO:774) is shown in bold; this coding portion starts at position 507 and ends at position 665. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P53 (SEQ ID NO:815) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
669 G -> A Yes
671 G -> A No
871 C -> No
959 A -> G No
967 C -> T No
973 C -> T Yes
1018 C -> T Yes
1071 C -> T No
1091 C -> T Yes
1197 G -> No
1209 G -> A Yes
1210 C -> No
1210 C -> T No
1299 A -> T No

Variant protein HSMUC1A_PEA—1_P56 (SEQ ID NO:816) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T42 (SEQ ID NO:780). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P56 (SEQ ID NO:816) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P56 (SEQ ID NO:816) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
117 P -> No

Variant protein HSMUC1A_PEA—1_P56 (SEQ ID NO:816) is encoded by the following transcript(s): HSMUC1A_PEA—1_T42 (SEQ ID NO:780), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T42 (SEQ ID NO:780) is shown in bold; this coding portion starts at position 507 and ends at position 890. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P56 (SEQ ID NO:816) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
855 C -> No
943 A -> G No
951 C -> T No
957 C -> T Yes
1002 C -> T Yes
1055 C -> T No
1075 C -> T Yes
1181 G -> No
1193 G -> A Yes
1194 C -> No
1194 C -> T No
1283 A -> T No

Variant protein HSMUC1A_PEA—1_P58 (SEQ ID NO:817) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T35 (SEQ ID NO:777). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P58 (SEQ ID NO:817) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 25, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P58 (SEQ ID NO:817) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25
Amino acid mutations
SNP position(s) on Alternative Previously
amino acid sequence amino acid(s) known SNP?
147 P -> No

Variant protein HSMUC1A_PEA—1_P58 (SEQ ID NO:817) is encoded by the following transcript(s): HSMUC1A_PEA—1_T35 (SEQ ID NO:777), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T35 (SEQ ID NO:777) is shown in bold; this coding portion starts at position 507 and ends at position 980. The transcript also has the following SNPs as listed in Table 26 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P58 (SEQ ID NO:817) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
945 C -> No
1033 A -> G No
1041 C -> T No
1047 C -> T Yes
1092 C -> T Yes
1145 C -> T No
1165 C -> T Yes
1271 G -> No
1283 G -> A Yes
1284 C -> No
1284 C -> T No
1373 A -> T No

Variant protein HSMUC1A_PEA—1_P59 (SEQ ID NO:818) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T28 (SEQ ID NO:771). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSMUC1A_PEA—1_P59 (SEQ ID NO:818) is encoded by the following transcript(s): HSMUC1A_PEA—1_T28 (SEQ ID NO:771), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T28 (SEQ ID NO:771) is shown in bold; this coding portion starts at position 507 and ends at position 794. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P59 (SEQ ID NO:818) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
794 G -> A Yes
796 G -> A No
996 C -> No
1084 A -> G No
1092 C -> T No
1098 C -> T Yes
1143 C -> T Yes
1196 C -> T No
1216 C -> T Yes
1322 G -> No
1334 G -> A Yes
1335 C -> No
1335 C -> T No
1424 A -> T No

Variant protein HSMUC1A_PEA—1_P63 (SEQ ID NO:819) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSMUC1A_PEA—1_T47 (SEQ ID NO:782). An alignment is given to the known protein (Mucin 1 precursor (SEQ ID NO:805) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSMUC1A_PEA—1_P63 (SEQ ID NO:819) and MUC1_HUMAN (SEQ ID NO:805):

1.An isolated chimeric polypeptide encoding for HSMUC1A_PEA—1_P63 (SEQ ID NO:819), comprising a first amino acid sequence being at least 90% homologous to MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSV corresponding to amino acids 1-45 of MUC1_HUMAN (SEQ ID NO:805), which also corresponds to amino acids 1-45 of HSMUC1A_PEA—1_P63 (SEQ ID NO:819), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK (SEQ ID NO:946) corresponding to amino acids 46-85 of HSMUC1A_PEA—1_P63 (SEQ ID NO:819), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSMUC1A_PEA—1_P63 (SEQ ID NO:819), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence

EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK (SEQ ID NO:946)
in HSMUC1A_PEA_1_P63. (SEQ ID NO:819)

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

The glycosylation sites of variant protein HSMUC1A_PEA—1_P63 (SEQ ID NO:819), as compared to the known protein Mucin 1 precursor (SEQ ID NO:805), are described in Table 28 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 28
Glycosylation site(s)
Position(s) on known Present in
amino acid sequence variant protein?
1055 no
957 no
975 no
1133 no
1029 no

Variant protein HSMUC1A_PEA—1_P63 (SEQ ID NO:819) is encoded by the following transcript(s): HSMUC1A_PEA—1_T47 (SEQ ID NO:782), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSMUC1A_PEA—1_T47 (SEQ ID NO:782) is shown in bold; this coding portion starts at position 507 and ends at position 761. The transcript also has the following SNPs as listed in Table 29 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSMUC1A_PEA—1_P63 (SEQ ID NO:819) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
572 A -> G No
900 A -> No
904 C -> No
963 A -> C Yes
1211 A -> G No
1219 C -> T No
1225 C -> T Yes
1270 C -> T Yes
1323 C -> T No
1343 C -> T Yes
1449 G -> No
1461 G -> A Yes
1462 C -> No
1462 C -> T No
1551 A -> T No

As noted above, cluster HSMUC1A features 22 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSMUC1A_PEA—1_node—0 (SEQ ID NO:783) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1 564
(SEQ ID NO:769)
HSMUC1A_PEA_1_T26 1 564
(SEQ ID NO:770)
HSMUC1A_PEA_1_T28 1 564
(SEQ ID NO:771)
HSMUC1A_PEA_1_T29 1 564
(SEQ ID NO:772)
HSMUC1A_PEA_1_T30 1 564
(SEQ ID NO:773)
HSMUC1A_PEA_1_T31 1 564
(SEQ ID NO:774)
HSMUC1A_PEA_1_T33 1 564
(SEQ ID NO:775)
HSMUC1A_PEA_1_T34 1 564
(SEQ ID NO:776)
HSMUC1A_PEA_1_T35 1 564
(SEQ ID NO:777)
HSMUC1A_PEA_1_T36 1 564
(SEQ ID NO:778)
HSMUC1A_PEA_1_T40 1 564
(SEQ ID NO:779)
HSMUC1A_PEA_1_T42 1 564
(SEQ ID NO:780)
HSMUC1A_PEA_1_T43 1 564
(SEQ ID NO:781)
HSMUC1A_PEA_1_T47 1 564
(SEQ ID NO:782)

Segment cluster HSMUC1A_PEA—1_node—14 (SEQ ID NO:784) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 666 841
(SEQ ID NO:769)

Segment cluster HSMUC1A_PEA—1_node—24 (SEQ ID NO:785) according to the present invention is supported by 135 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 953 1084
(SEQ ID NO:769)

Segment cluster HSMUC1A_PEA—1_node—29 (SEQ ID NO:786) according to the present invention is supported by 156 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780) and HSMUC1A_PEA—1_T43 (SEQ ID NO:781). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1207 1346
(SEQ ID NO:769)
HSMUC1A_PEA_1_T26 894 1033
(SEQ ID NO:770)
HSMUC1A_PEA_1_T28 913 1052
(SEQ ID NO:771)
HSMUC1A_PEA_1_T29 865 1004
(SEQ ID NO:772)
HSMUC1A_PEA_1_T30 838 977
(SEQ ID NO:773)
HSMUC1A_PEA_1_T31 788 927
(SEQ ID NO:774)
HSMUC1A_PEA_1_T33 881 1020
(SEQ ID NO:775)
HSMUC1A_PEA_1_T34 783 922
(SEQ ID NO:776)
HSMUC1A_PEA_1_T35 862 1001
(SEQ ID NO:777)
HSMUC1A_PEA_1_T36 756 895
(SEQ ID NO:778)
HSMUC1A_PEA_1_T40 762 901
(SEQ ID NO:779)
HSMUC1A_PEA_1_T42 772 911
(SEQ ID NO:780)
HSMUC1A_PEA_1_T43 693 832
(SEQ ID NO:781)

Segment cluster HSMUC1A_PEA—1_node—35 (SEQ ID NO:787) according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T47 666 1189
(SEQ ID NO:782)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (in relation to breast cancer), shown in Table 35.

TABLE 35
Oligonucleotides related to this segment
Oligonucleotide Overexpressed in Chip
name cancers reference
HSMUC1A_0_0_11365 breast malignant BRS
(SEQ ID NO:917) tumors

Segment cluster HSMUC1A_PEA—1_node—38 (SEQ ID NO:788) according to the present invention is supported by 140 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1488 1749
(SEQ ID NO:769)
HSMUC1A_PEA_1_T26 1175 1436
(SEQ ID NO:770)
HSMUC1A_PEA_1_T28 1194 1455
(SEQ ID NO:771)
HSMUC1A_PEA_1_T29 1146 1407
(SEQ ID NO:772)
HSMUC1A_PEA_1_T30 1119 1380
(SEQ ID NO:773)
HSMUC1A_PEA_1_T31 1069 1330
(SEQ ID NO:774)
HSMUC1A_PEA_1_T33 1162 1423
(SEQ ID NO:775)
HSMUC1A_PEA_1_T34 1064 1325
(SEQ ID NO:776)
HSMUC1A_PEA_1_T35 1143 1404
(SEQ ID NO:777)
HSMUC1A_PEA_1_T36 1037 1298
(SEQ ID NO:778)
HSMUC1A_PEA_1_T40 1043 1304
(SEQ ID NO:779)
HSMUC1A_PEA_1_T42 1053 1314
(SEQ ID NO:780)
HSMUC1A_PEA_1_T43 974 1235
(SEQ ID NO:781)
HSMUC1A_PEA_1_T47 1321 1582
(SEQ ID NO:782)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HSMUC1A_PEA—1_node—3 (SEQ ID NO:789) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T40 (SEQ ID NO:779) and HSMUC1A_PEA—1_T43 (SEQ ID NO:781). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T29 565 591
(SEQ ID NO:772)
HSMUC1A_PEA_1_T34 565 591
(SEQ ID NO:776)
HSMUC1A_PEA_1_T40 565 591
(SEQ ID NO:779)
HSMUC1A_PEA_1_T43 565 591
(SEQ ID NO:781)

Segment cluster HSMUC1A_PEA—1_node—4 (SEQ ID NO:790) according to the present invention can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 565 573
(SEQ ID NO:769)
HSMUC1A_PEA_1_T26 565 573
(SEQ ID NO:770)
HSMUC1A_PEA_1_T28 565 573
(SEQ ID NO:771)
HSMUC1A_PEA_1_T29 592 600
(SEQ ID NO:772)
HSMUC1A_PEA_1_T30 565 573
(SEQ ID NO:773)
HSMUC1A_PEA_1_T31 565 573
(SEQ ID NO:774)
HSMUC1A_PEA_1_T33 565 573
(SEQ ID NO:775)
HSMUC1A_PEA_1_T34 592 600
(SEQ ID NO:776)
HSMUC1A_PEA_1_T35 565 573
(SEQ ID NO:777)
HSMUC1A_PEA_1_T36 565 573
(SEQ ID NO:778)
HSMUC1A_PEA_1_T40 592 600
(SEQ ID NO:779)
HSMUC1A_PEA_1_T42 565 573
(SEQ ID NO:780)
HSMUC1A_PEA_1_T43 592 600
(SEQ ID NO:781)
HSMUC1A_PEA_1_T47 565 573
(SEQ ID NO:782)

Segment cluster HSMUC1A_PEA—1_node—5 (SEQ ID NO:791) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 574 600
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 574 600
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 574 600
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 601 627
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 574 600
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 574 600
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 574 600
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 601 627
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 574 600
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 574 600
(SEQ ID NO: 778)
HSMUC1A_PEA_1_T40 601 627
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 574 600
(SEQ ID NO: 780)
HSMUC1A_PEA_1_T43 601 627
(SEQ ID NO: 781)
HSMUC1A_PEA_1_T47 574 600
(SEQ ID NO: 782)

Segment cluster HSMUC1A_PEA—1_node—6 (SEQ ID NO:792) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 601 638
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 601 638
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 601 638
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 628 665
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 601 638
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 601 638
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 601 638
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 628 665
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 601 638
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 601 638
(SEQ ID NO: 778)
HSMUC1A_PEA_1_T40 628 665
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 601 638
(SEQ ID NO: 780)
HSMUC1A_PEA_1_T43 628 665
(SEQ ID NO: 781)
HSMUC1A_PEA_1_T47 601 638
(SEQ ID NO: 782)

Segment cluster HSMUC1A_PEA—1_node—7 (SEQ ID NO:793) according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780) and HSMUC1A_PEA—1_T43 (SEQ ID NO:781). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 639 665
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 639 665
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 639 665
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 666 692
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 639 665
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 639 665
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 639 665
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 666 692
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 639 665
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 639 665
(SEQ ID NO: 778)
HSMUC1A_PEA_1_T40 666 692
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 639 665
(SEQ ID NO: 780)
HSMUC1A_PEA_1_T43 666 692
(SEQ ID NO: 781)

Segment cluster HSMUC1A_PEA—1_node—17 (SEQ ID NO:794) according to the present invention can be found in the following transcript(s): HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T33 (SEQ ID NO:775) and HSMUC1A_PEA—1_T40 (SEQ ID NO:779). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T28 666 684
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T33 666 684
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T40 693 711
(SEQ ID NO: 779)

Segment cluster HSMUC1A_PEA—1_node—18 (SEQ ID NO:795) according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T40 (SEQ ID NO:779) and HSMUC1A_PEA—1_T42 (SEQ ID NO:780). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 842 891
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 666 715
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 685 734
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 693 742
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 666 715
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T33 685 734
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T35 666 715
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T40 712 761
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 666 715
(SEQ ID NO: 780)

Segment cluster HSMUC1A_PEA—1_node—20 (SEQ ID NO:796) according to the present invention can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T35 (SEQ ID NO:777) and HSMUC1A_PEA—1_T42 (SEQ ID NO:780). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 892 900
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 716 724
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 735 743
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T33 735 743
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T35 716 724
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T42 716 724
(SEQ ID NO: 780)

Segment cluster HSMUC1A_PEA—1_node—21 (SEQ ID NO:797) according to the present invention is supported by 97 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T35 (SEQ ID NO:777) and HSMUC1A_PEA—1_T42 (SEQ ID NO:780). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 901 947
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 725 771
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 744 790
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T33 744 790
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T35 725 771
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T42 725 771
(SEQ ID NO: 780)

Segment cluster HSMUC1A_PEA—1_node—23 (SEQ ID NO:798) according to the present invention can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 948 952
(SEQ ID NO: 769)

Segment cluster HSMUC1A_PEA—1_node—26 (SEQ ID NO:799) according to the present invention is supported by 129 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773) and HSMUC1A_PEA—1_T31 (SEQ ID NO:774). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1085 1116
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 772 803
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 791 822
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 743 774
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 716 747
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 666 697
(SEQ ID NO: 774)

Segment cluster HSMUC1A_PEA—1_node—27 (SEQ ID NO:800) according to the present invention is supported by 140 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777) and HSMUC1A_PEA—1_T36 (SEQ ID NO:778). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1117 1206
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 804 893
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 823 912
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 775 864
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 748 837
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 698 787
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 791 880
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 693 782
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 772 861
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 666 755
(SEQ ID NO: 778)

Segment cluster HSMUC1A_PEA—1_node—31 (SEQ ID NO:801) according to the present invention can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780) and HSMUC1A_PEA—1_T43 (SEQ ID NO:781). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1347 1356
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 1034 1043
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 1053 1062
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 1005 1014
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 978 987
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 928 937
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 1021 1030
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 923 932
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 1002 1011
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 896 905
(SEQ ID NO: 778)
HSMUC1A_PEA_1_T40 902 911
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 912 921
(SEQ ID NO: 780)
HSMUC1A_PEA_1_T43 833 842
(SEQ ID NO: 781)

Segment cluster HSMUC1A_PEA—1_node—34 (SEQ ID NO:802) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T47 639 665
(SEQ ID NO: 782)

Segment cluster HSMUC1A_PEA—1_node—36 (SEQ ID NO:803) according to the present invention is supported by 135 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1357 1388
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 1044 1075
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 1063 1094
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 1015 1046
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 988 1019
(SEQ ID NO: 773)
HSMUC1A_PEA_1_T31 938 969
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 1031 1062
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 933 964
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 1012 1043
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 906 937
(SEQ ID NO: 778)
HSMUC1A_PEA_1_T40 912 943
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 922 953
(SEQ ID NO: 780)
HSMUC1A_PEA_1_T43 843 874
(SEQ ID NO: 781)
HSMUC1A_PEA_1_T47 1190 1221
(SEQ ID NO: 782)

Segment cluster HSMUC1A_PEA—1_node—37 (SEQ ID NO:804) according to the present invention is supported by 146 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSMUC1A_PEA—1_T12 (SEQ ID NO:769), HSMUC1A_PEA—1_T26 (SEQ ID NO:770), HSMUC1A_PEA—1_T28 (SEQ ID NO:771), HSMUC1A_PEA—1_T29 (SEQ ID NO:772), HSMUC1A_PEA—1_T30 (SEQ ID NO:773), HSMUC1A_PEA—1_T31 (SEQ ID NO:774), HSMUC1A_PEA—1_T33 (SEQ ID NO:775), HSMUC1A_PEA—1_T34 (SEQ ID NO:776), HSMUC1A_PEA—1_T35 (SEQ ID NO:777), HSMUC1A_PEA—1_T36 (SEQ ID NO:778), HSMUC1A_PEA—1_T40 (SEQ ID NO:779), HSMUC1A_PEA—1_T42 (SEQ ID NO:780), HSMUC1A_PEA—1_T43 (SEQ ID NO:781) and HSMUC1A_PEA—1_T47 (SEQ ID NO:782). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSMUC1A_PEA_1_T12 1389 1487
(SEQ ID NO: 769)
HSMUC1A_PEA_1_T26 1076 1174
(SEQ ID NO: 770)
HSMUC1A_PEA_1_T28 1095 1193
(SEQ ID NO: 771)
HSMUC1A_PEA_1_T29 1047 1145
(SEQ ID NO: 772)
HSMUC1A_PEA_1_T30 1020 1118
(SEQ ID NO: 773)
HSMUCIA_PEA_1_T31 970 1068
(SEQ ID NO: 774)
HSMUC1A_PEA_1_T33 1063 1161
(SEQ ID NO: 775)
HSMUC1A_PEA_1_T34 965 1063
(SEQ ID NO: 776)
HSMUC1A_PEA_1_T35 1044 1142
(SEQ ID NO: 777)
HSMUC1A_PEA_1_T36 938 1036
(SEQ ID NO: 778)
HSMUC1A_PEA_1_T40 944 1042
(SEQ ID NO: 779)
HSMUC1A_PEA_1_T42 954 1052
(SEQ ID NO: 780)
HSMUC1A_PEA_1_T43 875 973
(SEQ ID NO: 781)
HSMUC1A_PEA_1_T47 1222 1320
(SEQ ID NO: 782)

Variant protein alignment to the previously known protein:

Sequence name: MUC1_HUMAN (SEQ ID NO:805)

Sequence documentation:

Alignment of: HSMUC1A_PEA—1_P63 (SEQ ID NO:819)×MUC1_HUMAN (SEQ ID NO:805).

Alignment segment 1/1:

Quality: 429.00
Escore: 0
Matching length: 59 Total length: 59
Matching Percent 86.44 Matching Percent Identity: 81.36
Similarity:
Total Percent Similarity: 86.44 Total Percent Identity: 81.36
Gaps: 0

Alignment:

         .         .         .         .         .
1 MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSVEEEVS 50
|||||||||||||||||||||||||||||||||||||||||||||
1 MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSVPSSTE 50
51 ADQVSVGAS 59
 : ||: :|
51 KNAVSMTSS 59

Combined Expression of 8 Sequences (T10888seg11-17 (SEQ ID NO: 832), HUMGR5E junc3-7 (SEQ ID NO: 857), HSSTROL3seg24 (SEQ ID NO: 869), T94936 Seg 14 (SEQ ID NO: 861), Z21368 seg39 (SEQ ID NO: 844), Z21368 junc17-21 (SEQ ID NO: 847), T59832 jun6-25-26 (SEQ ID NO: 854) and M85491seg24 (SEQ ID NO: 866)) in Normal and Cancerous Breast Tissues

Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6, GRP_HUMAN—gastrin-releasing peptide, Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3), Homo sapiens breast cancer membran protein 11 (BCMP11), SUL1_HUMAN, Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3 and gamma-interferon inducible lysosomal thiol recductase (GILT) transcripts detectable by or according to T10888seg11-17 (SEQ ID NO: 832), HUMGR5E junc3-7 (SEQ ID NO: 857), HSSTROL3seg24 (SEQ ID NO: 869), T94936 Seq 14 (SEQ ID NO: 861), Z21368 seg39 (SEQ ID NO: 844), Z21368 junc17-21 (SEQ ID NO: 874), T58832 jun6-25-26 (SEQ ID NO: 854) and M85491seg24 (SEQ ID NO: 866) amplicons and T10888seg11-17F (SEQ ID NO: 830), T10888seg11-17R (SEQ ID NO: 831), HUMGR5E junc3-7F(SEQ ID NO: 855), HUMGR5E junc3-7F (SEQ ID NO: 856), HSSTROL3seg24F (SEQ ID NO:867), HSSTROL3seg24R (SEQ ID NO: 868), T94936seg14F (SEQ ID NO: 859), T94936seg14R (SEQ ID NO: 860), Z21368 seg39F (SEQ ID NO: 842), Z21368 seg39R (SEQ ID NO: 843), Z21368junc17-21F (SEQ ID NO: 845), Z21368junc17-21R (SEQ ID NO: 846), T59832 jun6-25-26F (SEQ ID NO: 852), T59832 jun6-25-26F (SEQ ID NO: 853), M85491seg24F (SEQ ID NO: 864) and M85491seg24R (SEQ ID NO: 865) primers was measured by real time PCR. In parallel the expression of four housekeeping genes—PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon—PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM—000194 (SEQ ID NO:930); amplicon—HPRT1-amplicon (SEQ ID NO:933 ), G6PD (GenBank Accession No. NM—000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) and SDHA (GenBank Accession No. NM—004168 (SEQ ID NO:922); amplicon—SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicons was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample of each amplicon was then divided by the median of the quantities of the normal post-mortem (PM) samples detected for the same amplicon (Sample Nos. 56-60, 63-67 Table 1, “Tissue samples in testing panel” above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIGS. 44-47 are histograms showing differential expression of the above-indicated transcripts in cancerous breast samples relative to the normal samples, in different combinations. The number and percentage of samples that exhibit at least 5 fold differential of at least one of the sequences, out of the total number of samples tested is indicated in the bottom.

As is evident from FIGS. 44-47, differential expression of at least 5 fold in at least one of the sequences was found in 25 out of 28 adenocarcinoma samples in all different combinations.

Statistical analysis was applied to verify the significance of these results, as described below. Threshold of 5 fold differential expression of at least one of the amplicons was found to differentiate between cancer and normal samples.

The above values demonstrate statistical significance of the results.

Description for Cluster HSU33147

Cluster HSU33147 features 2 transcript(s) and 5 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1
Transcripts of interest
Transcript Name Sequence ID No.
HSU33147_PEA_1_T1 820
HSU33147_PEA_1_T2 821

TABLE 2
Segments of interest
Segment Name Sequence ID No.
HSU33147_PEA_1_node_0 822
HSU33147_PEA_1_node_2 823
HSU33147_PEA_1_node_4 824
HSU33147_PEA_1_node_7 825
HSU33147_PEA_1_node_3 826

TABLE 3
Proteins of interest
Sequence ID Corresponding
Protein Name No. Transcript(s)
HSU33147_PEA_1_P5 828 HSU33147_PEA_1_T1;
(SEQ ID NO: 820)
HSU33147_PEA_1_T2
(SEQ ID NO: 821)

These sequences are variants of the known protein Mammaglobin A precursor (SwissProt accession identifier MGBA_HUMAN; known also according to the synonyms Mammaglobin 1; Secretoglobin family 2A member 2), SEQ ID NO: 827, referred to herein as the previously known protein.

The sequence for protein Mammaglobin A precursor (SEQ ID NO:827) is given at the end of the application, as “Mammaglobin A precursor (SEQ ID NO:827) amino acid sequence”.

It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Immunostimulant. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anticancer.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: steroid binding, which are annotation(s) related to Molecular Function.

The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster HSU33147 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of FIG. 48 refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 48 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues.

TABLE 4
Normal tissue distribution
Name of Tissue Number
epithelial 6
general 2
lung 0
breast 131

TABLE 5
P values and ratios for expression in cancerous tissue
Name of Tissue P1 P2 SP1 R3 SP2 R4
epithelial 4.1e−02 6.4e−02 1.5e−12 2.6 2.2e−06 1.5
general 1.6e−02 1.1e−02 1.2e−22 4.4 7.2e−13 2.4
lung 1 6.3e−01 1 1.0 6.2e−01 1.6
breast 8.6e−02 1.1e−01 3.4e−07 1.7 2.6e−03 1.0

As noted above, cluster HSU33147 features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Mammaglobin A precursor (SEQ ID NO:827). A description of each variant protein according to the present invention is now provided.

Variant protein HSU33147_PEA—1_P5 (SEQ ID NO:828) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSU33147_PEA—1_T1 (SEQ ID NO:820). An alignment is given to the known protein (Mammaglobin A precursor (SEQ ID NO:827) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison report between HSU33147_PEA—1_P5 (SEQ ID NO:828) and MGBA_HUMAN (SEQ ID NO:827):

1.An isolated chimeric polypeptide encoding for HSU33147_PEA—1_P5 (SEQ ID NO:828), comprising a first amino acid sequence being at least 90% homologous to MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFIDDNATTNAI DELKECFLNQTDETLSNVE corresponding to amino acids 1-78 of MGBA_HUMAN (SEQ ID NO:827), which also corresponds to amino acids 1-78 of HSU33147_PEA—1_P5 (SEQ ID NO:828), and a second amino acid sequence being at least 90% homologous to QLIYDSSLCDLF corresponding to amino acids 82-93 of MGBA_HUMAN (SEQ ID NO:827) which also corresponds to amino acids 79-90 of HSU33147_PEA—1_P5 (SEQ ID NO:828), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2.An isolated chimeric polypeptide encoding for an edge portion of HSU33147_PEA—1_P5 (SEQ ID NO:828), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EQ, having a structure as follows: a sequence starting from any of amino acid numbers 78−x to 78; and ending at any of amino acid numbers 79+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

The glycosylation sites of variant protein HSU33147_PEA—1_P5 (SEQ ID NO:828), as compared to the known protein Mammaglobin A precursor (SEQ ID NO:827), are described in Table 6 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 6
Glycosylation site(s)
Position(s) on known amino Present in
acid sequence variant protein? Position in variant protein?
68 yes 68
53 yes 53

Variant protein HSU33147_PEA—1_P5 (SEQ ID NO:828) is encoded by the following transcript(s): HSU33147_PEA—1_T1 (SEQ ID NO:820), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSU33147_PEA—1_T1 (SEQ ID NO:820) is shown in bold; this coding portion starts at position 72 and ends at position 341. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSU33147_PEA—1_P5 (SEQ ID NO:828) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7
Nucleic acid SNPs
SNP position on Alternative Previously
nucleotide sequence nucleic acid known SNP?
84 A -> C No
124 C -> No
396 A -> G No

As noted above, cluster HSU33147 features 5 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSU33147_PEA—1_node—0 (SEQ ID NO:822) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSU33147_PEA—1_T1 (SEQ ID NO:820) and HSU33147_PEA—1_T2 (SEQ ID NO:821). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSU33147_PEA_1_T1 1 126
(SEQ ID NO: 820)
HSU33147_PEA_1_T2 1 126
(SEQ ID NO: 821)

Segment cluster HSU33147_PEA—1_node—2 (SEQ ID NO:823) according to the present invention is supported by 44 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSU33147_PEA—1_T1 (SEQ ID NO:820) and HSU33147_PEA—1_T2 (SEQ ID NO:821). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSU33147_PEA_1_T1 127 305
(SEQ ID NO: 820)
HSU33147_PEA_1_T2 127 305
(SEQ ID NO: 821)

Segment cluster HSU33147_PEA—1_node—4 (SEQ ID NO:824) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSU33147_PEA—1_T2 (SEQ ID NO:821). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSU33147_PEA_1_T2 315 907
(SEQ ID NO: 821)

Segment cluster HSU33147_PEA—1_node—7 (SEQ ID NO:825) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSU33147_PEA—1_T1 (SEQ ID NO:820). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSU33147_PEA_1_T1 306 516
(SEQ ID NO: 820)

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster HSU33147_PEA—1_node—3 (SEQ ID NO:826) according to the present invention can be found in the following transcript(s): HSU33147_PEA—1_T2 (SEQ ID NO:821) Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12
Segment location on transcripts
Segment Segment
starting ending
Transcript name position position
HSU33147_PEA_1_T2 306 314
(SEQ ID NO: 821)

Sequence name: MGBA_HUMAN (SEQ ID NO:827)

Sequence documentation:

Alignment of: HSU33147_PEA—1_P5 (SEQ ID NO:828)×MGBA_HUMAN (SEQ ID NO:827).

Alignment segment 1/1:

Quality: 776.00
Escore: 0
Matching length: 90 Total length: 93
Matching Percent 100.00 Matching Percent Identity: 100.00
Similarity:
Total Percent Similarity: 96.77 Total Percent Identity: 96.77
Gaps: 1

Alignment:

         .         .         .         .         .
1 MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFI 50
||||||||||||||||||||||||||||||||||||||||||||||||||
1 MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFI 50
         .         .         .         .
51 DDNATTNAIDELKECFLNQTDETLSNVE...QLIYDSSLCDLF 90
||||||||||||||||||||||||||||   ||||||||||||
51 DDNATTNAIDELKECFLNQTDETLSNVEVFMQLIYDSSLCDLF 93

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

Claims

1. An isolated polynucleotide comprising a polynucleotide having a sequence of R11723_PEA—1_T5 (SEQ ID NO:560).

2. The isolated polynucleotide of claim 1, comprising a node having a sequence of: R11723_PEA—1_node—13(SEQ ID NO:562).

3. An isolated polypeptide comprising a polypeptide having a sequence of: R11723_PEA—1_P13 (SEQ ID NO:591).

4. The isolated polypeptide of claim 3, comprising a chimeric polypeptide encoding for R11723_PEA—1_P13 (SEQ ID NO:591), comprising a first amino acid sequence being at least 95% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:886), which also corresponds to amino acids 1-63 of R11723_PEA—1_P13 (SEQ ID NO:591), and a second amino acid sequence being at least about 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) corresponding to amino acids 64-84 of R11723_PEA—1_P13 (SEQ ID NO:591), wherein said first and second amino acid sequences are contiguous and in a sequential order.

4. (canceled)

5. The isolated polynucleotide of claim 1, comprising an amplicon according to SEQ ID NO: 975.

6. A primer pair, comprising a pair of isolated oligonucleotides capable of amplifying said amplicon of claim 5.

7. The primer pair of claim 6, comprising a pair of isolated oligonucleotides: SEQ NOs 973 and 974.

8. An antibody capable of specifically binding to an epitope of an amino acid sequence (SEQ ID NO:591) of claim 3.

10. The antibody of claim 8, wherein said antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein PSEC (SEQ ID NO:886).

11. A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to claim 1.

12. The kit of claim 11, wherein said kit comprises a NAT-based technology.

12. (canceled)

13. (canceled)

14. (canceled)

15. The method of claim 26, wherein said detecting overexpression is performed with a NAT-based technology.

16. A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to claim 3, wherein said detecting overexpression is performed with an immunoassay.

18. A biomarker capable of detecting breast cancer, comprising a nucleic acid sequence according to claim 1 or a fragment thereof, or an amino acid sequence according to claim 3 or a fragment thereof.

19. A method for screening for breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18.

20. A method for diagnosing breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18.

21. A method for monitoring disease progression and/or treatment efficacy and/or relapse of breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18.

22. A method of selecting a therapy for breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18 and selecting a therapy according to said detection.

23. The isolated polypeptide of claim 4, comprising a tail of R11723_PEA—1_P13 (SEQ ID NO:591), comprising a polypeptide being at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) in R11723_PEA—1_P13 (SEQ ID NO:591).

24. A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to claim 3, said kit comprising an antibody according to claim 8.

25. The kit of claim 24, wherein said kit further comprises at least one reagent for performing an ELISA or a Western blot.

26. A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to claim 1.

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