EP1713827A2 - Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease - Google Patents

Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease

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Publication number
EP1713827A2
EP1713827A2 EP05726249A EP05726249A EP1713827A2 EP 1713827 A2 EP1713827 A2 EP 1713827A2 EP 05726249 A EP05726249 A EP 05726249A EP 05726249 A EP05726249 A EP 05726249A EP 1713827 A2 EP1713827 A2 EP 1713827A2
Authority
EP
European Patent Office
Prior art keywords
seq
amino acid
amino acids
sequence
homologous
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05726249A
Other languages
German (de)
French (fr)
Inventor
Yossi Cohen
Alexander Diber
Amir Toporik
Sarah Pollock
Zurit Levine
Michal Ayalon-Soffer
Gad S. Cojocaru
Amit Novik
Guy Kol
Osnat Sella-Tavor
Shira Walach
Shirley Sameah-Greenwald
Dvir Dahary
Ronen Shemesh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Compugen Ltd
Original Assignee
Compugen Ltd
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Filing date
Publication date
Application filed by Compugen Ltd filed Critical Compugen Ltd
Priority claimed from US11/043,788 external-priority patent/US20060014166A1/en
Publication of EP1713827A2 publication Critical patent/EP1713827A2/en
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6887—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from muscle, cartilage or connective tissue
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders

Definitions

  • the present invention is related to novel nucleotide and protein sequences that are diagnostic markers for cardiac disease and/or pathological conditions, including cardiac damage, and assays and methods of use thereof.
  • Cardiovascular diseases are an important cause of mortality and morbidity. Amongst all age groups considered, IHD is the most common cause of death not only in men but also in women. Coronary atherosclerosis is a chronic progressing process, associated with angina type symptoms and frequently result in Acute Myocardial Infarction (AMI). The diagnosis is achieved with a combination of patient physical examination, ECG since 1950's molecular markers play the most important role in the differential diagnosis of AMI from other conditions with similar symptoms. Early diagnosis is mandatory of the establishment of early treatment (including blood diluting agents, thrombolysis, catheterization and surgery). Early molecular markers for AMI were SGOT and LDH were proved to be of very low specificity and are hardly being used at present.
  • CPK-MB heart specific CPK-MB variant. Its specificity is better than for SGOT and LDH, it is still limited both in specificity and sensitivity which reach only 67% when used together with electrocardiogram.
  • cardiac surgery, myocarditis, and electrical cardioversion often result in elevated serum levels ofthe CPK-MB isoenryme. Small infarct with minor myocardial cell necrosis often do not increase serum CPK-MB to a detected level.
  • Myoglobin is another heart damage low molecular (17kD) protem but is even less specific to heart muscle compared with CPK-MB. Its advantage over CPK-MB is a rapid rise from the onset of symptoms - usually between 3-6 hours.
  • Cardiac troponins are currently the routine serum cardiac markers used for the diagnosis of AMI.
  • Troponin-I and Troponin-T have amino acid sequences different from those of the skeletal muscle called cTnT and cTnl (cardiac Troponin-T and I recpectively).
  • Cardiac troponins are not found in the serum of healthy individuals and rise to up to 20 times above a predefined cut-off level, therefore are very useful and sensitive in the detection of cardiac damage.
  • Cardiac troponin's sensitivity is considerably higher than CPK-MB but they suffer from a few disadvantages: 1. They are not early markers - cTnl and cTnT reach peak serum value in about 12 and 48 hours respectively after symptoms onset. 2. Levels of cTnl and cTnT remain elevated for up to 10 days and 14 days respectively after AMI, therefore cannot be used for the detection of re- infarction. 3. Other heart diseases such as Congestive Heart Failure and Myocarditis can increase troponins concentrations in the serum.
  • H-FABP Heart Fatty Acid binding protein
  • the heart specific variant H-FABP is a low molecular protein (15Kd) soluble non- enzyme protein. H-FABP concentration in the heart muscle is greater than that in skeletal muscle, and its normal baseline concentration is several fold lower than myoglobin. In addition, it reaches peak value in the urine and blood early, within 2-3 hours from AMI.
  • HFABP has higher sensitivity - up to 80% - when compared with other cardiac markers (CPK-MB and the troponins sensitivity were reported to be 64% in the first 6 hours after AMI). Yet, H-FABP still misses every 5f h patient in this time scale. H-FABP has other limitations as well, including 1. rising in the plasma after exercise 2. released from muscle in skeletal damage during the course of AMI (like from intramuscular injections) 3. reduced clearance in renal failure situations. The search for novel cardiac damage markers is ongoing. Other proteins are under trials for that purpose including glycogen phosphorylase BB, HIF and VEGF 21.
  • cardiac disease and/or pathology and/or condition and/or disorder may comprise one or more of Myocardial infarct, acute coronary syndrome, angina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure or any type of heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, assessing the size of infarct in Myocardial infarct, the differential diagnosis of heart related conditions from lung related conditions (as pulmonary embolism), the differential diagnosis of Dyspnea, and cardiac valves related conditions.
  • suitable biological samples include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, and any human organ or tissue.
  • the biological sample comprises cardiac tissue and/or a serum sample and/or a urine sample and/or any other tissue or liquid sample.
  • the sample can optionally be diluted with a suitable eluant before contacting the sample to the antibody.
  • signalpjimm 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 detennined through manual inspection of known protein localization and/or gene structure, and the use of heuristics by the individual inventor.
  • T - > C means that the SNP results in a change at the position given in the table from T to C.
  • M - > Q 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 (*).
  • 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 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.
  • 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.
  • tissue name was used as the reference to the type of chip for which expression was measured.
  • 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, CA, USA (see for example data regarding the Human Genome U133 (HG-U133) Set at www.affymeftix.com products/arrays/specific/hgul33.affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.com/products/arrays/specific/hgul33av2.affx; and Human Genome U133 Plus 2.0 Array at www.affymetrix.com/products/arrays/specific/hgul33plus.affx).
  • the probe names follow the Affymetrix naming convention.
  • ADP adipocyte
  • BM bone marrow
  • BRS mammary gland
  • CAR cartilage
  • CNS central nervous system
  • E-ADR endocrine_adrenal_gland
  • E-PAN endocrine_pancreas
  • HN head and neck
  • LN lymph node
  • PNS peripheral nervous system
  • TCELL immune T cells
  • THYM thymus
  • adipocyte "Al”; “adrenalcortex”, “A2”; “adrenalgland”, “A3”; “amygdala”, “A4"; “appendix”, “A5"; “atrioventricularnode”, “A6”; “bm_cdl 05_endothelial”, “El”; “bm_cd33_myeloid”, “Ml”;
  • testisseminiferoustubule , "S6";
  • nucleic acid sequences of the present invention 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.
  • ohgonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary ohgonucleotides may optionally be derived, and/or for any other use.
  • cardiac disease includes any type of cardiac pathology and/or disorder and/or damage, including both chronic and acute damage, as well as progression from acute to chronic damage of the heart, and also propagation of one acute event to another acute event.
  • An example of the latter may occur when an infarct is followed by another infarct in a relatively short period of time, such as within 24 hours for example.
  • An infarct may also lead to acute heart failure immediately after the infarct, as another example.
  • marker in the context of the present invention lefers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from patients having a cardiac disease, such as acute cardiac damage for example, as compared to a comparable sample taken from subjects who do not have cardiac disease.
  • a cardiac disease such as acute cardiac damage for example
  • the phrase “differentially present” refers to differences in the quantity of a marker present in a sample talcen from patients having cardiac disease as compared to a comparable sample taken from patients who do not have cardiac disease.
  • 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.
  • a marker such as a protein or fragment thereof
  • a marker could optionally be present in a blood sample from the patient, indicating the presence of damage; lack of presence of such a marker (and/or presence at a low level) would therefore optionally and preferably indicate a lack of such damage.
  • chronically damaged heart might cause a low level of the marker to be present in the blood sample, while acute damage would cause a high level to be present.
  • One of ordinary skill in the art could easily detennine such relative levels of the markers; further guidance is provided in the description of each individual marker below.
  • 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.
  • Diagnosing refers to classifying a disease or a symptom, determining a severity ofthe disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery.
  • the term “detecting” may also optionally encompass any ofthe 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.
  • 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.
  • the term "level” refers to expression levels of RNA and/or protein or to DNA copy number of a marker ofthe present invention.
  • 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 ofthe 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.
  • a “test amount” of a marker refers to an amount of a marker present in a sample being tested.
  • a test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).
  • 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 cardiac disease.
  • 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.
  • a control amount of a marker can be the amount of a marker in a patient with cardiac disease or a person without cardiac disease.
  • 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.
  • useful labels include 32 P, 35 S, 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.
  • 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. Fahr lander 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 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.
  • 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 ofthe 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 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.
  • 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 protem 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.
  • immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein.
  • solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A
  • a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.
  • a isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NO: 1
  • an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 1, 2, 3 and 4.
  • an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 281, 282, 283 and 284.
  • an isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NOs: 281, 282, 283 and 284.
  • an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 5, 6, 7, 8, 9 and 10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 5, 6, 7, 8, 9 and 10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID
  • an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93 and 94 .
  • an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93 and 94 .
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 12, 13, 14, 15, 16 and 17
  • an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112.
  • an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 292, 293, 294, 295 and 296
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 18 and 19.
  • ai isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 113, 114, 115, 116, 117, 118, 119, 120, 121 and 122.
  • an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 297 and 298.
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 20 and 21.
  • an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 123, 124, 125, 126, 127, 128 and 129.
  • an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 299 and 300.
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 26, 27, 28, 29 and 30.
  • ati isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162 and 163.
  • an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 305; 306; 307 and 308
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 31, 32, 33, 34, 35, 36 and 37.
  • an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185 and 186
  • an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 309, 310, 311 and 312.
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 38, 39, 40 and 41.
  • an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 187, 188, 189, 190, 191, 192, 193, 194, 195 and 196.
  • ⁇ isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 313, 314, 315 and 316.
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 42, 43, 44, 45, 46, 47, 48, 49 and 50.
  • an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207 and 208.
  • an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP
  • an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs:51, 52, 53, 54, 55, 56, 57, 58, 59 and 60.
  • an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 209 to 273.
  • an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 326 to 334.
  • ai isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NOs: 22-25, 353 or 386.
  • an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 130-149.
  • an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 301-304, 325, 354-356 or 387. According to prefe ⁇ ed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO.
  • a first amino acid sequence being at least 90 % homologous to amino acids 1 - 1855 of SEQ ID NO.338, which also co ⁇ esponds to amino acids 1 - 1855 of SEQ ID NO.326, 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 sequence corresponding to amino acids 1856 - 1904 of SEQ ID NO. 326, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT in SEQ ID NO. 326.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 327 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 1326 of SEQ ID NO. 339, which also co ⁇ esponds to amino acids 1 - 1326 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 1327 - 1336 of SEQ ID NO. 327, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • 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 VRPSGEGGQA in SEQ ID NO. 327.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 328 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 1508 of SEQ ID NO. 339, which also co ⁇ esponds to amino acids 1 - 1508 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 1509 - 1534 of SEQ ID NO. 328, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 329 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 1763 of SEQ ID NO. 338, which also co ⁇ esponds to amino acids 1 - 1763 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 1764 - 1788 of SEQ ID NO. 329, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 330 comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%o, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence co ⁇ esponding to amino acids 1 - 22 of SEQ ID NO.
  • 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 MGLWKPGSVLSDSLFASSPCPQ of SEQ ID NO. 330.
  • ai isolated chimeric polypeptide encoding for SEQ ID NO. 331 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 527 of SEQ ID NO. 339, which also co ⁇ esponds to amino acids 1 - 527 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 528 - 555 of SEQ ID NO. 331, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • polypeptide 331 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 VPPWPHHLCPLLCHPDKVVAESLLHPRN in SEQ ID NO. 331.
  • an isolated chimeric polypeptide encoding for SEQ ID NO.332 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 470 of SEQ ID NO.338, which also co ⁇ esponds to amino acids 1 - 470 of SEQ ID NO.332, a second amino acid sequence being at least 90 % homologous to amino acids 528 - 1855 of SEQ ID NO.338, which also co ⁇ esponds to amino acids 471 - 1798 of SEQ ID NO.332, 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 sequence co ⁇ esponding to amino acids 1799 - 1847 of SEQ ID NO.332, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in
  • an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO.332, 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 ainino 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 DP, having a structure as follows: a sequence starting from any of amino acid numbers 470-x to 470; and ending at any of amino acid numbers 471+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric plypeptide encoding for SEQ ID N0.333 comprising a first amino acid sequence being at least 90 % homologous to amino acids 165 - 1939 of SEQ ID NO. 340, which also co ⁇ esponds to amino acids 1 - 1775 of SEQ ID NO.333.
  • an isolated chimeric polypeptide encoding for SEQ ID NO.334 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1165 - 1939 of SEQ ID NO.
  • an isolated chimeric polypeptide encoding for SEQ ID N0.317 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 158 of SEQ ID NO. 341, which also co ⁇ esponds to amino acids 1 - 158 of SEQ ID N0.317.
  • an isolated chimeric polypeptide encoding for SEQ ID N0.318 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 156 of SEQ ID NO.
  • an isolated polypeptide encoding for a tail of SEQ ID NO.318, 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
  • VSVGQECGSG in SEQ ID NO.318.
  • an isolated chimeric polypeptide encoding for SEQ ID N0.319 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 156 of SEQ ID NO.
  • an isolated polypeptide encoding for a tail of SEQ ID NO.319 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY in SEQ ID NO.319 .
  • a first amino acid sequence being at least 90 % homologous to amino acids 1 - 60 of Q96NR4, which also co ⁇ esponds to amino acids 1 - 60 of SEQ ID NO. 320, 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 sequence co ⁇ esponding to amino acids 61 - 114 of SEQ ID NO. 320, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 320 comprising a first amino acid sequence being at least 90 % homologous to amino acids 97 - 156 of SEQ ID NO. 341, which also co ⁇ esponds to amino acids 1 - 60 of SEQ ID NO.
  • a second amino acid sequence bridging amino acid sequence comprising of S and a third amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 62 - 133 of SEQ ID NO. 342, which also corresponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.
  • 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies from 0 to n-2.
  • 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 sequence co ⁇ esponding to amino acids 1 - 15 of SEQ ID NO. 321, and a second amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 39 - 110 of SEQ ID NO. 343, which also co ⁇ esponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies
  • ai isolated polypeptide encoding for a tail of SEQ ID NO. 320 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY in SEQ ID NO. 320.
  • first amino acid sequence being at least 90 % homologous to conesponding to amino acids 1 - 14 of SEQ ID NO. 342, which also co ⁇ esponds to amino acids 1 - 14 of SEQ ID NO. 321, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 62 - 133 of SEQ ID NO. 342, which also co ⁇ esponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.
  • ai isolated polypeptide encoding for an edge portion of SEQ ID NO. 321, 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 VSI having a structure as follows (numbering according to SEQ ID NO.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 321, 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 sequence corresponding to amino acids 1 - 15 of SEQ ID NO.
  • 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 MRGEHNSTSYDSAVS of SEQ ID NO. 321.
  • a second amino acid sequence bridging amino acid sequence comprising of S and a third amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 158 - 229 of SEQ ID NO. 341, which also co ⁇ esponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.
  • 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 322. 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 sequence co ⁇ esponding to amino acids 1 - 23 of SEQ ID NO.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 322. comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 97 - 158 of SEQ ID NO. 341., which also co ⁇ esponds to amino acids 1 - 62 of SEQ ID NO. 322..
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 324 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 60 of SEQ ID NO. 342, which also co ⁇ esponds to amino acids 1 - 60 of SEQ ID NO. 324, 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 sequence co ⁇ esponding to amino acids 61 - 70 of SEQ ID NO.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 324 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 VSVGQECGSG in SEQ ID NO. 324.
  • 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 sequence co ⁇ esponding to amino acids 1 - 23 of SEQ ID NO. 324, a second amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 37 of SEQ ID NO. 343, which also co ⁇ esponds to amino acids 24 - 60 of SEQ ID NO.
  • 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 co ⁇ esponding to amino acids 61 - 70 of SEQ ID NO. 324, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.
  • 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 MRGEHNSTSYDSAVIYRGFWAVL of SEQ ID NO. 324.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 324 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
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 324 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 97 - 156 of SEQ ID NO. 341, which also corresponds to amino acids 1 - 60 of SEQ ID NO. 324, 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 co ⁇ esponding to amino acids 61 - 70 of SEQ ID NO.
  • a isolated polypeptide encoding for a tail of SEQ ID NO. 324 comprising a polypeptide being at least 70%o, 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 VSVGQECGSG in SEQ ID NO. 324.
  • first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 115 of SEQ ID NO. 344, which also co ⁇ esponds to amino acids 1 - 115 of SEQ ID NO. 313, and a second amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 152 - 319 of SEQ ID NO. 344, which also co ⁇ esponds to amino acids 116 - 283 of SEQ ID NO. 313, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 313, of cluster Z36249 comprising a first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 -
  • 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 sequence co ⁇ esponding to amino acids 185 - 197 of SEQ ID NO. 314, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • 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 IY, having a structure as follows: a sequence starting from any of amino acid numbers 115-x to 115; and ending at any of amino acid numbers 116+ ((n-2) - x), in which x varies from 0 to n-2.
  • first amino acid sequence being at least 90 % homologous to co ⁇ esponding to amino acids 1 - 151 of SEQ ID NO. 344, which also co ⁇ esponds to amino acids 1 - 151 of SEQ ID NO. 315
  • 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 sequence co ⁇ esponding to amino acids 152 - 177 of SEQ ID NO. 315, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 315 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 VRLMQSTAKSSSLILCFLCFTPVLLI in SEQ ID NO. 315.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 315 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 70 of SEQ ID NO.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 315 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 VRLMQSTAKSSSLILCFLCFTPVLLI in SEQ ID NO. 315.
  • 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 EL, having a structure as follows: a sequence starting from any of amino acid numbers 151-x to 151; and ending at any of amino acid numbers 152+ ((n-2) - x), in which x varies from 0 to n-2.
  • 316 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 70 of SEQ ID NO. 345, which also co ⁇ esponds to amino acids 1 - 70 of SEQ ID NO. 316, a bridging amino acid K conesponding to amino acid 71 of SEQ ID NO. 316, a second amino acid sequence being at least 90 % homologous to amino acids 72 - 151 of SEQ ID NO. 345, which also conesponds to amino acids 72 - 151 of SEQ ID NO. 316, and a third amino acid sequence being at least 90 % homologous to amino acids 185 - 319 of SEQ ID NO.
  • cluster Z36249 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 EL, having a structure as follows: a sequence starting from any of amino acid numbers 151-x to 151; and ending at any of amino acid numbers 152+ ((n-2) - x), in which x varies from 0 to n-2.
  • a third amino acid sequence being at least 70%, optionally at least 80%o, preferably at least 85%, more preferably at least 90%> and most preferably at least 95%> homologous to a polypeptide sequence co ⁇ esponding to amino acids
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 309 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 VRPHLTLKAPLGLRMHRDPLRTPSPKSWPLTQPLTPDATLTPQAILTPTLT in SEQ ID NO. 309.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 310 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 42 of SEQ ID NO. 346, which also conesponds to amino acids 1 - 42 of SEQ ID NO. 310, a bridging amino acid N co ⁇ esponding to amino acid 43 of SEQ ID NO. 310, a second amino acid sequence being at least 90 % homologous to amino acids 44 - 676 of SEQ ID NO. 346, which also co ⁇ esponds to amino acids 44 - 676 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 677 - 685 of SEQ ID NO. 310, 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.
  • a second amino acid sequence being at least 90 %> homologous to amino acids 44 - 657 of SEQ ID NO. 346, which also conesponds to amino acids 44 - 657 of SEQ ID NO. 311, 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 sequence co ⁇ esponding to amino acids 658 - 696 of SEQ ID NO. 311, 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.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 311 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 GPGRHAGNAGTLTQSLDCDAGVPPPAFQPLSTSYIYFSE in SEQ ID NO. 311.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 312 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 42 of SEQ ID NO.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 305 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 381 of SEQ ID NO. 347, which also co ⁇ esponds to amino acids 1 - 381 of SEQ ID NO.
  • a second amino acid sequence being at least 10%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence co ⁇ esponding to amino acids 382 - 387 of SEQ ID NO. 305, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 306 comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 338 of SEQ ID NO. 347, which also co ⁇ esponds to amino acids 1 - 338 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 339 - 346 of SEQ ID NO. 306, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 307 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 223 of SEQ ID NO. 347, which also co ⁇ esponds to amino acids 1 - 223 of SEQ ID NO.
  • 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% homobgous to a polypeptide sequence co ⁇ esponding to amino acids 117 - 215 of SEQ ID NO. 281, wherein said firstand second amino acid sequences are contiguous and in a sequential order.
  • 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRWSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL in SEQ ID NO. 281.
  • 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRWSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL in SEQ ID NO. 281.
  • 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 sequence co ⁇ esponding to amino acids 1 - 116 of FABH HUMAN, which also co ⁇ esponds to amino acids 1 - 116 of SEQ ID NO. 282, 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 sequence conesponding to amino acids 117 - 178 of SEQ ID NO. 282, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 282 comprismg 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 DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in SEQ ID NO. 282.
  • a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also co ⁇ esponds to amino acids 1 - 116 of SEQ ID NO. 282, 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%o homologous to a polypeptide sequence conesponding to amino acids 117 - 178 of SEQ ID NO. 282, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • polypeptide being at least 70%
  • a polypeptide being at least 70%
  • most preferably at least about 95% > homologous to the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG According to prefened embodiments of the present invention, there is provided ai isolated chimeric polypeptide encoding for SEQ ID NO.
  • 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 amino acids 1 - 116 of FABHJHUMAN, which also conesponds to amino acids 1 - 116 of SEQ ID NO. 283, 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 sequence co ⁇ esponding to amino acids 117 - 126 of SEQ ID NO. 283, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 283, 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 MEKLQLRNVK in SEQ ID NO. 283.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 283, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also co ⁇ esponds to amino acids SEQ ID NO.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 283, comprising a polypeptide being at least 70%o, 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
  • a third amino acid sequence being at least 90 % homologous to amino acids 25 - 133 of FABH HUMAN, which also co ⁇ esponds to amino acids 36 - 144 of SEQ ID NO. 284, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.
  • 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 sequence co ⁇ esponding to amino acids 25 - 35 of SEQ ID NO. 284, and a third amino acid sequence being at least 90 % homologous to amino acids 25 - 133 of AAP35373, which also co ⁇ esponds to amino acids 36 - 144 of SEQ ID NO. 284, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • 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 sequence co ⁇ esponding to amino acids 204 - 240 of SEQ ID NO. 285, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • 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 sequence conesponding to amino acids 79 - 125 of SEQ ID NO. 286, and a third amino acid sequence being at least 90 % homologous to amino acids 79 - 399 of SEQ ID NO. 349, which also co ⁇ esponds to amino acids 126 - 446 of SEQ ID NO. 286, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for an edge portion of SEQ ID NO. 286, 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
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 287 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 140 of SEQ ID NO. 349, which also co ⁇ esponds to amino acids 1 - 140 of SEQ ID NO. 287, and a second amino acid sequence being at least 90 % homologous to amino acids 203 - 399 of SEQ ID NO. 349, which also conesponds to amino acids 141 - 337 of SEQ ID NO.
  • an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 287 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 DV, having a structure as follows: a sequence starting from any of amino acid numbers 140-x to 140; and ending at any of amino acid numbers 141+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encodmg for SEQ ID NO. 288, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%o, more preferably at least 90% > and most preferably at least 95% homologous to a polypeptide sequence co ⁇ esponding to amino acids 1 - 10 of SEQ ID NO. 288, second amino acid sequence being at least 90 % homologous to amino acids 18 - 106 of SEQ ID NO. 349, which also co ⁇ esponds to amino acids 11 - 99 of SEQ ID NO.
  • a third (bridging) amino acid sequence comprising D, and a fourth amino acid sequence being at least 90 % homologous to amino acids 179 - 399 of SEQ ID NO. 349, which also conesponds to amino acids 101 - 321 of SEQ ID NO. 288, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.
  • polypeptide 288, comprising a polypeptide being at least 10%), 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 NETEAEQSYV ofSEQ ID NO. 288.
  • a polypeptide being at least 10%
  • 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 LDY having a structure as follows (numbering according to SEQ ID NO. 288): a sequence starting from any of amino acid numbers 99-x to 99; and ending at any of amino acid numbers 101 + ((n-2) - x), in which x varies from 0 to n-2.
  • 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 sequence co ⁇ esponding to amino acids 1 - 15 of SEQ ID NO. 289, and a second amino acid sequence being at least 90 %> homologous to co ⁇ esponding to amino acids 203 - 399 of SEQ ID NO. 349, which also co ⁇ esponds to amino acids 16 - 212 of SEQ ID NO. 289, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a head of SEQ ID NO. 289 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% homobgous to the sequence MSSWLSAGSPSSLSV of SEQ ID NO. 289.
  • 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 sequence co ⁇ esponding to amino acids 1 - 13 of SEQ ID NO. 290, and a second amino acid sequence being at least 90 % homologous to amino acids 280 - 399 of SEQ ID NO. 349, which also co ⁇ esponds to amino acids 14 - 133 of SEQ ID NO. 290, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • a isolated polypeptide encoding for a head of SEQ ID NO. 290 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
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 291 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%o and most preferably at least about 95% homologous to the sequence SRNWTQ in SEQ ID NO. 291.
  • 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 sequence co ⁇ esponding to amino acids 1 - 10 of SEQ ID NO. 292, second amino acid sequence being at least 90 % homologous to amino acids 26 - 276 of Q96NF5, which also co ⁇ esponds to amino acids 11 - 261 of SEQ ID NO. 292, followed by A, and a third amino acid sequence being at least 90 %> homologous to amino acids 278 - 466 of Q96NF5, which also co ⁇ esponds to amino acids 263 - 451 of SEQ ID NO.
  • an isolated polypeptide encoding for a head of SEQ ID NO. 292 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 MEISLVKCSE of SEQ ID NO. 292
  • 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 EE, having a structure as follows: a sequence starting from any of amino acid numbers 372-x to 372; and ending at any of amino acid numbers 373+ ((n-2) - x), in which x varies from 0 to n-2.
  • a first amino acid sequence being at least 90 % homologous to amino acids 1 - 276 of Q96NF5, which also conesponds to amino acids 1 - 276 of SEQ ID NO. 294, followed by A, a second amino acid sequence being at least 90 % homologous to amino acids 278 - 401 of Q96NF5, which also co ⁇ esponds to amino acids 278 - 401 of SEQ ID NO. 294, 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 sequence co ⁇ esponding to amino acids 402 - 407 of SEQ ID NO.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 295 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 276 of Q96NF5, which also conesponds to amino acids 1 - 276 of SEQ ID NO. 295, followed by A, a second amino acid sequence being at least 90 %> homologous to amino acids 278 - 374 of Q96NF5, which also conesponds to amino acids 278 - 374 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 375 - 390 of SEQ ID NO. 295, wherein said first, A, second and third amino acid sequences are contiguous and in a sequential order.
  • a polypeptide being at least 70%
  • a second amino acid sequence comprising A, and a third amino acid sequence being at least 90 % homologous to amino acids 263 - 451 of Q96NF5, which also co ⁇ esponds to amino acids 263 - 451 of SEQ ID NO. 296, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 297 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 132 of Q9NPI5, which also co ⁇ esponds to amino acids 1 - 132 of SEQ ID NO.
  • a second amino acid sequence being at least 70%o, optionally at least 80%>, preferably at least 85%, more preferably at least 90%) and most preferably at least 95% homologous to a polypeptide sequence conesponding to amino acids 133 - 145 of SEQ ID NO. 297, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 297 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 109 of Q9NZK3, which also co ⁇ esponds to amino acids 1 - 109 of SEQ ID NO.
  • 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 sequence co ⁇ esponding to amino acids 110 - 145 of SEQ ID NO. 297, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • 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 LVDLYSRRYFLTVPYEECKWRRSLPGRHEVPRGALP in SEQ ID NO. 297.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 298, 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
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 298, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 107 of Q9NZK3, which also conesponds to amino acids 1 - 107 of SEQ ID NO. 298, 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 sequence conesponding to amino acids 108 - 121 of SEQ ID NO.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 298, 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 NLPGRHEVPRGALP in SEQ ID NO. 298.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 300 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 MSSFSTTT co ⁇ esponding to amino acids 1 - 8 of SEQ ID NO.
  • an isolated polypeptide encoding for a head of SEQ ID NO. 300 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 MSSFSTTT of SEQ ID NO. 300.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 301 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 124 of TRIC_HUMAN, which also conesponds to amino acids 1 - 124 of SEQ ID NO. 301, 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 sequence conesponding to amino acids 125- 137 of SEQ ID NO. 301, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 301 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 VGRMGSSGTFGVG in SEQ ID NO. 301.
  • first amino acid sequence being at least 90 %> homologous to amino acids 1 - 8 of TRIC HUMAN, which also conesponds to amino acids 1 - 8 of SEQ ID NO. 302, 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 sequence conesponding to amino acids 36 - 209 of TRIC_HUMAN, which also conesponding to amino acids 9 - 182 of SEQ ID NO. 302, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 302, 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 AK, having a structure as follows: a sequence starting from any of amino acid numbers 8-x to 8; and ending at any of amino acid numbers 9+ ((n-2) - x), in which x varies from 0 to n-2.
  • an isolated chimeric polypeptide encoding for SEQ ID NO. 303 comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 36 of TRICJHUMA , which also co ⁇ esponds to amino acids 1 - 36 of SEQ ID NO. 303, 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 sequence conesponding to amino acids 37- 86 of SEQ ID NO. 303, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an isolated polypeptide encoding for a tail of SEQ ID NO. 303 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 VGRGFLGAEYRRRRDPRPWEWGEEPGLRRGRGLRGGASGAEFCRGSCSDW in SEQ ID NO. 303.
  • a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 8 of TPJC_HUMAN, which also conesponds to amino acids 1 - 8 of SEQ ID NO. 304, 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 sequence co ⁇ esponding to amino acids 9- 13 of SEQ ID NO. 304, wherein said first and second amino acid sequences are contiguous and in a sequential order.
  • an antibody capable of specifically binding to an epitope of an amino acid sequence in any one of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK,
  • kits for detecting heart disorders comprising a kit detecting overexpression of a splice variant.
  • the kit comprises a NAT-based technology.
  • the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence in any one of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK, H88495, Z36249, FLJ26352, HSACMHCP.
  • the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence in any one of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK, H88495, Z36249, FLJ26352, HSACMHCP.
  • kit comprises an antibody as described herein.
  • the kit further comprises at least one reagent for performing an ELISA or a Western blot.
  • at least one reagent for performing an ELISA or a Western blot comprising detecting overexpression of a splice variant of any of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK,
  • detecting overexpression is performed with a NAT-based technology.
  • detecting overexpression is performed with an immunoassay.
  • the immunoassay comprises an antibody as described herein.
  • a biomarker capable of detecting heart disorders comprising any of the above nucleic acid sequences or a fragment thereof, or amino acid sequences or a fragment thereof.
  • a method for screening for heart disorders comprising detecting cardiac disease cells or tissue with a biomarker or an antibody.
  • a method for diagnosing heart disorders comprising detecting heart cells or tissue with a biomarker or an antibody.
  • a method for monitoring disease progression, or treatment efficacy, or relapse of heart disorders, or any combination thereof comprising detecting heart cells or tissue with a biomarker or an antibody or a method or assay as described herein.
  • a method of selecting a therapy for heart disorders comprising detecting heart disorder cells with a biomarker or an antibody or a method or assay as described herein and selecting a therapy according to the detection.
  • a heart disorder and/or cardiac disease and/or cardiac pathology optionally comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, assessing the size of infarct in Myocardial infarct.
  • 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.
  • 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), ohgonucleotides (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.
  • Figure 1 shows a schematic summary of quantitative real-time PCR analysis.
  • Figure 2 is a histogram showing expression of ESTs in each category, as "parts per million”.
  • Figures 3 & 4 are histograms showing expression of ohgonucleotides in various tissues, prob 205738_s_at & prob 214285_at.
  • Figure 5A is a histogram showing specific expression of variant FABH_HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues.
  • Figure 5B is a histogram showing specific expression of variant FABH_HUMAN protein transcripts.
  • Figure 6 is a histrogram showing expression of FABH HUMAN known protein transcripts.
  • Figure 7 is a histogram showing expression of the number of heart tissue-specific clones in libraries/sequences.
  • Figure 8 is a histogram showing the actual expression of ohgonucleotides in various tissues, including heart tissue, prob 207317_s_at.
  • Figure 9 is a histogram showing specific expression of the above- indicated Calsequestrin, cardiac muscle isoform transcripts in sequence N56180, heart tissue samples.
  • Figure 10 is a histogram showing specific expression of the above -indicated
  • Calsequestrin cardiac muscle isoform transcripts in heart tissue samples as opposed to other tissues.
  • Figure 11 is a histogram showing expression of concerning the number of heart tissue- specific clones in libraries/sequences.
  • Figure 12 is a histogram showing specific expression of Q96NF5 transcripts in sequence
  • FIG. 13 is a histogram showing specific expression of the Q96NF5 transcripts in sequence T10377 junc29-33 heart tissue samples.
  • Figure 14 is a histogram showing specific expression of the above- indicated Q96NF5 transcripts T10377 seg2-3 in heart tissue samples.
  • Figure 15 is a histogram concerning the expression of the number of heart-specific clones in libraries/sequences.
  • Figure 16 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 221051_s_at, including heart.
  • Figure 17A is a histogram concerning the expressions of ESTs in number of heart tissue- specific clones in libraries/sequences;
  • Figure 17B is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 209957_s-at, including heart tissue.
  • Figure 18 is a histogram showing expression of known protein transcript for HUMCDDANF_T4.
  • Figure 19 is a histogram concerning expression of ESTs, the number of heart tissue- specific clones in libraries/sequences
  • Figure 20 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 205742_at, including heart tissue.
  • Figure 21A is a histogram showing specific expression of the above- indicated TRIC_HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts in sequence HUMTROPIA seglO in heart tissue.
  • Figure 21 A is a histogram showing specific expression of the TRIC_HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts in sequence HUMTROPIA seg22 in heart tissue.
  • Figure 22 is a histogram showing specific expression ofthe HUMTROPIA known protein sequence in heart tissue.
  • Figure 23 is a histogram showing ESTs concerning the number of heart tissue -specific clones in libraries/sequences
  • Figure 24 is a histogram concerning the actual expression of ohgonucleotides in various tissues, pob 205295_at, including heart tissue.
  • Figure 25 is a histogram showing ESTs concerning the number of heart tissue -specific clones in libraries/sequences
  • Figure 26 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 207066_at, including heart tissue.
  • Figure 27 is a histogram showing ESTs concerning the number of heart- specific clones in libraries/sequences.
  • Figure 28 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 206029_at, including heart tissue.
  • Figure 29 is a histogram concerning expression of ESTs in the number of heart tissue - specific clones in libraries/sequences.
  • Figure 30 is a histogram concerning the expression of ESTs in number of heart tissue- specific clones in libraries/sequences;
  • Figure 31 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 204737_s_at, including heart tissue.
  • Figure 32 is a histogram concerning the actual expression of oligonucleotides in various tissues, prob 216265_x_at, including heart tissue.
  • Figure 33 shows a diagram of a troponin I variant, HUMTROPIA_T7, with regard to introducing a mutation to block an additional ORF.
  • Figure 34 shows Troponin PCR product after second amplification reaction: Lane 1: 1Kb MW marker (GibcoBRL Cat# 15615-016) and Lane 2: PCR product.
  • Figure 35 shows Troponin PCR product sequence.
  • Figure 36 plasmid map of His Troponin T7 pRSET A.
  • Figure 37 shows the complete sequence ofthe plasmid shown in Figure 36.
  • Figure 38 shows the protein sequence of Troponin variant HUMTROPIA_PEA_2 T7, with the HIS-tag marked.
  • Figure 39a shows Coomassie staining analysis of SDS-PAGE containing recombinant HisTroponin; lane 1: Molecular weight marker (ProSieve color, Cambrex, Cat #50550); lane 2: HisTroponinT7 pRSETA TO; lane 3: pRSET A T3; lane 4: pRSET empty vector TO (negative control); lane 5: pRSET empty vector T3 (negative control).
  • Figure 39b shows a Western blot analysis of recombinant HisTroponin: lane 1: His positive control protein; lane 2: HisTro ⁇ oninT7 pRSETA TO; lane 3: HisTroponinT7 pRSETA T3; lane 4: pRSET empty vector TO (negative control); lane 5: pRSET empty vector T3
  • the present invention is of novel markers for cardiac disease that are both sensitive and accurate. 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, and/or are otherwise expressed at a much higher level and/or specifically expressed in heart.
  • the method of the present invention identifies clusters (genes) which are characterized in that the transcripts are differentially expressed in heart muscle tissue compared with other normal tissues, preferably in comparison to skeletal muscle tissue.
  • clusters genes which are characterized in that the transcripts are differentially expressed in heart muscle tissue compared with other normal tissues, preferably in comparison to skeletal muscle tissue.
  • hypoxia with or without necrosis
  • intracellular proteins that are not normally secreted can leak through the cell membrane to the extracellular space. Therefore, heart muscle tissue differentially expressed proteins, as through analysis of EST expression, are potential acute heart damage markers. Leakage of intracellular content can also occur in chronic damage to the heart muscle, therefore proteins selected according to this method are potential markers for chronic heart conditions.
  • BNP brain natriuretic peptide
  • ANF atrial natriuretic factor
  • the markers described herein are overexpressed in heart as opposed to muscle, as described in greater detail below.
  • the measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can co ⁇ elate with a probable diagnosis of cardiac disease and/or cardiac pathology, including but not limited to cardiac damage.
  • the present invention therefore also relates to diagnostic assays for cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, and methods of use of such markers for detection of cardiac disease and/or cardiac pathology, including but not limited to cardiac damage (alone or in combination), optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample.
  • the present invention therefore also relates to diagnostic assays for cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, and methods of use of such markers for detection of cardiac disease and/or cardiac pathology, including but not limited to cardiac damage (alorie or in combination), optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample.
  • 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.
  • 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 ofthe splice variant is typically highly homologous (often 100% identical) to a portion of the conesponding known protein, while at least a second portion of the variant comprises the tail.
  • 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.
  • 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 ofthe conesponding known protein.
  • 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.
  • the "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.
  • 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.
  • bridges are described with regard ⁇ o a sliding window in certain contexts below.
  • a bridge between two edges may optionally be described as follows: a bridge portion of CONTIG-NAME_Pl (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_Pl): 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) -
  • 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 co ⁇ esponding known protein (such known proteins are discussed with regard to their splice variants in the Examples below).
  • 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.
  • 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.
  • this invention provides an oligonucleotide of at least about 12 nucleotides, specifically hybridizable with the nucleic acid molecules of this invention.
  • this invention provides vectors, cells, liposomes and compositions comprising the isolated nucleic acids of this invention.
  • 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 co ⁇ esponding 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 co ⁇ elates with the presence of a splice variant in the biological sample.
  • 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 co ⁇ elates with the presence of a splice variant nucleic acid sequence in the biological sample.
  • the splice variants described herein are non-limiting examples of markers for diagnosing cardiac disease and/or cardiac pathology, including but not limited to cardiac damage.
  • 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage.
  • 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.
  • 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.
  • the known marker comprises the "known protein" as described in greater detail below with regard to each cluster or gene.
  • 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, such that a biomarker may optionally comprise any of the above.
  • the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence co ⁇ esponding 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, conesponding to a splice variant ofthe 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 occu ⁇ ing 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 %, at 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 occu ⁇ ing 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.
  • 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 ofthe 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 ofthe above).
  • cDNA complementary polynucleotide sequence
  • genomic polynucleotide sequence e.g., a combination ofthe above.
  • composite polynucleotide sequences e.g., a combination ofthe above.
  • 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.
  • genomic polynucleotide sequence refers to a sequence derived (isolated) from a chromosome and thus it represents a contiguous portion of a chromosome.
  • 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.
  • Prefe ⁇ ed 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).
  • 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.
  • 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.
  • 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 bio markers ofthe present invention.
  • the oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3' to 5' phosphodiester linkage.
  • oligonucleotides are those modified at one or more of the backbone, internucleoside linkages or bases, as is broadly described hereinunder.
  • Specific examples of prefe ⁇ ed 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.
  • Prefe ⁇ ed modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'.
  • 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.
  • morpholino linkages formed in part from the sugar portion of a nucleoside
  • siloxane backbones sulfide, sulfoxide and sulfone backbones
  • fo ⁇ uacetyl and thioformacetyl backbones methylene fonnacetyl and thioformacetyl backbones
  • alkene containing backbones sulfamate backbones
  • sulfonate and sulfonamide backbones amide backbones
  • others having mixed N, O, S and CEfe component parts, as disclosed in U.S. Pat. Nos.
  • 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).
  • PNA peptide nucleic acid
  • United States 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.
  • Oligonucleotides of the present invention may also include base modifications or substitutions.
  • "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-thio alkyl, 8-hydroxyl and other 8- substituted adenines and guanines, 5- halo particularly 5-bromo, 5-trifluoromethyl and other 5- substituted uracils and
  • 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 0-6 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 prefe ⁇ ed base substitutions, even more particularly when combined with 2'-0-methoxyethyl sugar modifications.
  • 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.
  • 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 palmity
  • 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.
  • 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.
  • 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.
  • the promoter utilized by the nucleic acid construct of the present invention is active in the specific cell population transformed.
  • 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.
  • 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.
  • the nucleic acid construct utilized is a shuttle vector, which can propagate both in E.
  • 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.
  • 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).
  • retroviral vector and packaging systems are those sold by Clontech, San Diego, Calif, rncludingRetro-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 5'LTR promoter.
  • Cu ⁇ ently prefened 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.
  • lipids for lipid- mediated transfer of the gene are, for example, DOTMA, DOPE, and DC-Choi [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)].
  • the most prefe ⁇ ed 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 aheady present in the viral construct.
  • a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed.
  • the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the polypeptide variants of the present invention.
  • the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence.
  • such constructs will typically include a 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' 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, Cu ⁇ ent Opin. Biotechnol. 10:71-75).
  • kits containing probes on a dipstick setup and the like 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.
  • 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 NaCI, 1 %> SDS and 5 x 10 ⁇ cpm 32 P labeled probe, at 65 °C, with a final wash solution of 0.2 x 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 NaCI, 1 % SDS and 5 x 10 6 cpm 32 P labeled probe, at 65 °C, with a final wash solution of 1 x SSC and 0.1 % SDS and final wash at 50 °C.
  • a hybridization solution such as containing 10 % dextrane sulfate, 1 M NaCI, 1 %> SDS and 5 x 10 ⁇ cpm 32 P labeled probe, at 65 °C
  • moderate hybridization is effected using a hybrid
  • hybridization of short nucleic acids can be effected using the following exemplary hybridization protocols which can be modified according to the desired stringency;
  • hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected.
  • 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.
  • detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies.
  • 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.
  • oligonucleotide probes 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.
  • probes can be labeled according to numerous well known methods.
  • radioactive nucleotides can be incorporated into probes of the invention by several methods.
  • Non- limiting examples of radioactive labels include 3 H, 14 C, 32 P, and 35 S.
  • Probes of the invention can be utilized with naturally occuning 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.
  • RNA ribonucleic acid
  • DNA deoxyribonucleic acid
  • NAT-based 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).
  • a "primer" defines an oligonucleotide which is capable of annealing to
  • 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. Natl. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTeclmology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol, 28:253-260; and Sambrook et al., 1989, supra).
  • PCR polymerase chain reaction
  • LCR ligase chain reaction
  • SDA strand displacement amplification
  • amplification 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.
  • amplification processes include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based amplification, as explained in greater detail below.
  • the oligos are designed to bind to a complementary sequence under selected conditions.
  • 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.
  • RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA.
  • the amplification of the differentially expressed nucleic acids is ca ⁇ ied 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.
  • 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.
  • 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 Cu ⁇ ent 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.
  • PCR 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 ⁇ /., 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.
  • 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.
  • Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes refe ⁇ ed to as “Ligase Amplification Reaction” (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids.
  • 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.
  • ligase will covalently link each set of hybridized molecules.
  • 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 Al (1990).
  • 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 unifo ⁇ n 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 5' end of the sequence of interest.
  • 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 (Q ⁇ ) Replicase In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for Q ⁇ replicase.
  • 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.
  • 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.
  • 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.
  • 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.
  • any background products that amplify with a better mean efficiency than the intended target will become the dominant products.
  • PCR has yet to penetrate the clinical market in a significant way.
  • LCR LCR must also be optimized to use different oligonucleotide sequences for each target sequence.
  • both methods require expensive equipment, capable of precise temperature cycling.
  • 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 3' 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 ofthe 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 3'-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the the ⁇ nostable ligase, but LCR still has the drawback of target- independent background ligation products initiating the amplification.
  • the direct detection method may be, for example a cycling probe reaction (CPR) or a branched DNA analysis.
  • CPR cycling probe reaction
  • branched DNA analysis e.g., a method that does not amplify the signal exponentially is more amenable to quantitative analysis.
  • CPR Cycling probe reaction
  • 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 canied through sample preparation.
  • Branched DNA 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 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).
  • RFLP analysis restriction fragment length polymorphism
  • ASO allele specific oligonucleotide
  • DGGE/TGGE Denaturing/Temperature Gradient Gel Electrophoresis
  • SSCP Single-Strand Conformation Polymorphism
  • ddF Dideoxy fingerprinting
  • test sample e.g., a bacterial isolate
  • amplified material e.g., PCR reaction products
  • This avoids the time and expense associated with cloning the segment of interest.
  • 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.
  • 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 ofthe 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.
  • a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis).
  • RFLP restriction fragment length polymorphism
  • 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).
  • MCC Mismatch Chemical Cleavage
  • RFLP analysis suffers from low sensitivity and requires a large amount of sample.
  • 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.
  • 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.
  • Allele specific oligonucleotide 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 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.
  • DGGE/TGGE Denaturing/Temperature Gradient Gel Electrophoresis
  • the fragments to be analyzed are "clamped" at one end by a long stretch of GC base pahs (30-80) to allow complete denaturation ofthe 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.
  • DGGE constant denaturant gel electrophoresis
  • 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.
  • 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.
  • 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).
  • all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed.
  • 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.
  • 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.
  • 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.
  • the step of searching for any ofthe 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, Q ⁇ -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.
  • any suitable technique including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, Q ⁇ -Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific oligonucleotides, denaturing
  • 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.
  • the identity ofthe 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.
  • polypeptide amino acid sequences and peptides
  • polypeptide amino acid sequences and peptides
  • polypeptide polypeptide
  • peptide amino acid residues
  • protein 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 co ⁇ esponding 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.
  • polypeptide polypeptide
  • polypeptide polypeptide
  • 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 Monow 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.
  • 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.
  • NCBI National Center of Biotechnology Information
  • nucleic acid sequence homology is determined 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.
  • NBI National Center of Biotechnology Information
  • 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 occu ⁇ ing or artificially induced, either randomly or in a targeted fashion.
  • 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.
  • Trp, Tyr and Phe may be substituted for synthetic non- natural acid such as Phenylglycme, TIC, naphthylelanine (Nol), ring- methylated derivatives of Phe, halogenated derivatives of Phe or o- methyl- Tyr.
  • 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 ) .
  • 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.
  • amino acid includes bothD- and L- amino acids.
  • 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.
  • Antibodies 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., Fab' and F(ab)' 2 fragments.
  • antibody 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, CHI, CH2 and CH3, but does not include the heavy chain variable region.
  • Fab the fragment which contains a monovalent antigen-binding fragment of an antibody molecule
  • Fab' 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 Fab' fragments are obtained per antibody molecule
  • (Fab')2 the fragment ofthe antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction
  • F(ab')2 is a dimer of two Fab' fragments held together by two disulfide bonds
  • 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
  • SCA Single chain antibody
  • Antibody fragments according to the present invention can be prepared by proteolytic hydrolysis ofthe 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(ab')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 Fab' monovalent fragments.
  • a thiol reducing agent optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages
  • an enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly.
  • 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].
  • the variable chains can be linked by an intermolecular disulfide bond or cross- linked by chemicals such as glutaraldehyde.
  • the Fv fragments comprise VH and VL chains connected by a peptide linker.
  • sFv single- chain antigen binding proteins
  • sFv single-chain antigen binding proteins
  • 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 etal., Science 242:423-426 (1988); Pack et al., Bio/Technology 11:1271-77 (1993); and U.S.
  • CDR complementarity- dete ⁇ nining region
  • Another form of an antibody fragment is a peptide coding for a single complementarity- dete ⁇ nining 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, Fab', F(ab') 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.
  • CDR complementary determining region
  • Fv framework residues of the human immunoglobulin are replaced by co ⁇ esponding 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.
  • 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 conespond 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, Cu ⁇ . Op. Struct. Biol., 2:593-596 (1992)].
  • Fc immunoglobulin constant region
  • Methods for humanizing non-human antibodies are well known in the art.
  • 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 refened 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 co ⁇ esponding 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 co ⁇ esponding sequence from a non-human species.
  • 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.
  • human antibodies can be made by introduction of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes ha ⁇ e been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rea ⁇ angement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos.
  • the antibody of this aspect of the present invention specifically binds at least one epitope of the polypeptide variants of the present invention.
  • 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.
  • 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.
  • 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 ofthe antibody bound to the marker in the sample.
  • 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.
  • EIA enzyme immune assay
  • ELISA enzyme- linked immunosorbent assay
  • RIA radioimmune assay
  • Western blot assay e.g., Western blot assay, or a slot blot assay see, e.g., U.S. Pat. Nos.
  • a sample obtained from a subject can be contacted with the antibody that specifically binds the marker.
  • 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.
  • 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.
  • 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.
  • 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.
  • the immunoassay can be used to determine a test amount of a marker in a sample from a subject.
  • 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.
  • 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.
  • antibodies which specifically interact with the polypeptides of the present invention and not with wild type proteins or other isofo ⁇ ns 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.
  • Prefe ⁇ ed embodiments of antibodies according to the present invention are described in greater detail with regard to the section entitled "Antibodies”.
  • Radio -immunoassay In one version, this method involves precipitation of the desired substrate and in the methods detailed hereinbelow, with a specific antibody and 125 radiolabelled antibody binding protein (e.g., protein A labeled with f ) immobilized on a precipitable carrier such as agarose beads. The number of counts in the precipitated pellet is proportional to the amount of substrate.
  • 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 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 ofthe 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 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 ofthe present invention.
  • display vehicles such as phages, viruses or bacteria
  • 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); US patent No: 6,625,545; and U.S. Pat. Appl. 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.
  • 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.
  • sequence information particularly of spliced sequences
  • chromosomal information particularly of spliced sequences
  • 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.
  • the potential markers were identified by a computational process mat was designed to find genes and/or their splice variants that are specifically expressed in cardiac tissue, as opposed to other types of tissues and also particularly as opposed to muscle tissue, by using databases of expressed sequences.
  • 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 specifically expressed in heart tissue is described hereinbelow.
  • EST analysis ESTs were taken from the following main sources: libraries contained in Genbank version 136 (June 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gbl36.release.notes) and Genbank version 139 (December 2003); and from the LifeSeq library of Incyte Corporation (ESTs only; Wilmington, DE, USA). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section were used. Library annotation - EST libraries were manually classified according to: 1. Tissue origin 2.
  • Biological source - Examples of frequently used biological sources for construction of EST libraries include cancer cell- lines; normal tissues; cancer tissues; foetal 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.
  • 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 (described in the annotation available in Genbank). It will be appreciated that at times the protocol of library construction is not indicated in the information available about that library. The following rules were followed: EST libraries originating from identical biological samples were 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.
  • heart tissue libraries/sequences were compared to the total number of libraries/sequences in the cluster and in Genebank, and to the relevant numbers for muscle tissue libraries/sequences.
  • Statistical tools were employed to identify clusters that were heart tissue specific, both as compared to all other tissues and also in comparison to muscle 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
  • This ratio was preferably set to be at least about 4, although optionally the ratio could be set to be at least about 2.
  • P- values were computed for weighted clone counts to check that the counts are statistically significant according to the following function: F(t,T,n,N) which is the probability of a cluster actually being overexpressed in heart tissue, as compared to its overall level of expression.
  • the P-value was preferably set to be less than about le-5, although optionally it could be set to be less than about le-3.
  • RNA preparation - RNA was obtained from Clontech (Franklin Lakes, NJ USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com), ABS (Wilmington, DE 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, TX 78744 USA, http://www.ambion.com).
  • 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 DNasel (Ambion) and purified using RNeasy columns (Qiagen).
  • RT PCR - Purified RNA (1 ⁇ g) was mixed with 150 ng Random Hexamer primers (Invitrogen) and 500 ⁇ M dNTP in a total volume of 15.6 ⁇ l. The mixture was incubated for 5 min at 65 °C and then quickly chilled on ice. Thereafter, 5 ⁇ l of 5X Superscriptll first strand buffer (Invitrogen), 2.4 ⁇ l 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.
  • 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 no ⁇ nalized to the geometric mean of the relative quantities of several housekeeping (HSKP) genes.
  • RT reverse transcription
  • HSKP housekeeping
  • RPL19 Forward primer TGGCAAGAAGAAGGTCTGGTTAG
  • Reverse primer TGATCAGCCCATCTTTGATGAG
  • RPL19 -amplicon
  • TATA box (GenBank Accession No. NM_003194), TATA box Forward primer : CGGTTTGCTGCGGTAATCAT TATA box Reverse primer: TTTCTTGCTGCCAGTCTGGAC
  • Ubiquitin (GenBank Accession No. BC000449)
  • Ubiquitin Forward primer ATTTGGGTCGCGGTTCTTG
  • Ubiquitin Reverse primer TGCCTTGACATTCTCGATGGT
  • Ubiquitin -amplicon
  • SDHA (GenBank Accession No. NM_004168) SDHA Forward primer: TGGGAACAAGAGGGCATCTG
  • SDHA Reverse primer CCACCACTGCATCAAATTCATG SDHA- amplicon : TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT AGTGGATCATGAATTTGATGCAGTGGTGG
  • Cluster S67314 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.
  • Protein Fatty acid-binding protein, heart is known or believed to have the following funct ⁇ on(s): FABP are thought to play a role in the intracellular transport of long- chain fatty acids and their acyl-CoA esters.
  • the sequence for protein Fatty acid-binding protein, heart is given at the end of the application, as "Fatty acid-binding protein, heart amino acid sequence" (SEQ ID NO:348). Known polymorphisms for this sequence are as shown in Table 4.
  • Protein Fatty acid-binding protein, heart localization is believed to be Cytoplasmic.
  • the following GO Annotation(s) apply to the previously known protein.
  • the following annotation(s) were found: negative control of cell proliferation, which are annotation(s) related to Biological Process; and lipid 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/>.
  • the heart-selective diagnostic marker prediction engine provided the following results with regard to cluster S67314. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods.
  • the numbers on the y-axis of Figure 2 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).
  • the histogram in Figure 2 concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figures 3 - 4, concerning the actual expression of oligonucleotides in various tissues, including heart.
  • This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 13.8; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 2.6; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be l.lOE-25.
  • cluster S67314 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Fatty acid- binding protein, heart.
  • Variant protein S67314_PEA_1_P4 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T4.
  • An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end ofthe 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 l O i follows:
  • Comparison report between S67314JPEA_1_P4 and FABH_HUMAN l.An isolated chimeric polypeptide encoding for S67314JPEA_1_P4, comprising a first amino acid sequence being at least 70%>, optionally at least 80%, preferably at least 85%o, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence
  • Comparison report between S67314_PEA_1_P4 and AAP35373 l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P4, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSrVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL conesponding to amino acids 1 - 116 of AAP35373, which also co ⁇ esponds to amino acids 1 - 116 of S67314_PEA_1_P4, and a second amino acid sequence being at least 70%, optionally at least 80%o, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRWATLELYLIGYYYCSFSQACSKKPSPP
  • polypeptide encoding for a tail of S67314_PEA_1_P4, 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGTNNTNLVGLLGSL in S67314_PEA_1_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: intracellularly.
  • the protein bcalization is believed to be intracellular 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 S67314_PEA_1_P4 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 S67314_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein S67314JPEA_1_P4 is encoded by the following transcript(s): S67314JPEA_1_T4, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript S67314_PEA_1_T4 is shown in bold; this coding portion starts at position 925 and ends at position 1569.
  • 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 S67314JPEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs
  • Variant protein S67314_PEA_1_P5 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T5.
  • An alignment is given to the known protein (Fatty acid-binding protein, heart) 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.
  • polypeptide encoding for a tail of S67314_PEA_1_P5, 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 DVLTAWPSIYPvRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in S67314 PEA 1 P5.
  • 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.
  • variant protein S67314_PEA_1_P5 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 S67314_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein accordmg to the present invention).
  • Table 7 - Amino acid mutations Single Nucleotide Polymorphisms
  • Variant protein S67314_PEA_1_P5 is encoded by the following transcript(s): S67314_PEA_1_T5, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript S67314_PEA_1_T5 is shown in bold; this coding portion starts at position 925 and ends at position 1458.
  • the transcript also has the following SNPs as listed in Tabte 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 S67314_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs
  • Variant protein S67314_PEA_1_P6 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T6.
  • An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end ofthe 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 S67314_PEA_1_P6 and FABHJHUMAN l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P6, 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 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL co ⁇ esponding to amino acids 1 - 116 of FABH_HUMAN, which also co ⁇ esponds to amino acids 1 - 116 of S67314_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at
  • polypeptide encoding for a tail of S67314_PEA_1_P6, 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 MEKLQLRNVK in S67314_PEA_1_P6.
  • the location of the variant protein was detennined 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: mtracellularly.
  • variant protein S67314_PEA_1_P6 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 S67314_PEA_1_P6 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 amino acid(s) Previously known SNP? sequence 53 K -> R Yes
  • Variant protein S67314_PEA_1_P6 is encoded by the following xranscript(s): S67314__PEA_1_T6, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript S67314_PEA_1_T6 is shown in bold; this coding portion starts at position 925 and ends at position 1302.
  • 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 S67314_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein S67314_PEA_1_P7 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T7.
  • An alignment is given to the known protein (Fatty acid -binding protein, heart) at the end ofthe 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 S67314_PEA_1_P7 and FABHJHUMAN l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSL co ⁇ esponding to amino acids 1 - 24 of FABH_HUMAN, which also co ⁇ esponds to amino acids 1 - 24 of S67314_PEA_1_P7, 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 AHILITFPLPS conesponding to amino acids 25 - 35 of S67314_PEA_1_P7, and a third amino acid sequence being at least 90 %> homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTE
  • an isolated polypeptide encoding for an edge portion of S67314_PEA_1_P7 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 AHILITFPLPS, co ⁇ esponding to S67314_PEA_1_P7.
  • Comparison report between S67314_PEA_1 JP7 and AAP35373 l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to
  • MVDAFLGTWKLVDSKNFDDYMKSL co ⁇ esponding to amino acids 1 - 24 of AAP35373, which also conesponds to amino acids 1 - 24 of S67314_PEA_1_P7, 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
  • AHILITFPLPS co ⁇ esponding to amino acids 25 - 35 of S67314_PEA_1_P7, and a third amino acid sequence being at least 90 % homologous to
  • VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA co ⁇ esponding to amino acids 25 - 133 of AAP35373, which also co ⁇ esponds to amino acids 36 - 144 of
  • S67314_PEA_1_P7 wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
  • An isolated polypeptide encoding for an edge portion of S67314_PEA_1_P7 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 AHILITFPLPS, co ⁇ esponding to S67314_PEA_1_P7.
  • the location of the variant protein was detennined 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 intracellular 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 S67314_PEA_1_P7 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 S67314_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 11 - Amino acid mutations Single Nucleotide Polymorphisms
  • Variant protein S67314_PEA_1_P7 is encoded by the following transcript(s): S67314_PEA_1_T7, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript S67314_PEA_1_T7 is shown in bold; this coding portion starts at position 925 and ends at position 1356.
  • 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 S67314_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • cluster S67314 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 S67314_PEA_l_node_0 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): S67314_PEA_1_T4, S67314_PEA_1_T5, S67314_PEA_1_T6 and S67314_ PEA_1_T7. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts
  • Segment cluster S67314_PEA_l_node_l l is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T4. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts
  • Segment cluster S67314_PEA_l_node_13 is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T7. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts
  • Segment cluster S67314_PEA_l_node_15 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
  • Segment cluster S67314_PEA_l_node_17 is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T6. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts
  • Segment cluster S67314JPEA_l_node_4 is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T4, S67314_PEA_1_T5, S67314_PEA_1_T6 and S67314_PEA_1_T7. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts
  • segment cluster S67314_PEA_l_node_10 is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T4, S67314_PEA_1_T5, S67314_PEA_1_T6 and S67314_PEA_1_T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
  • Segment cluster S67314_PEA_l_node_3 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T7. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
  • FABH_HUMAN Fatty acid-binding protein transcripts which are detectable by amplicon as depicted in sequence name S67314 specifically in heart tissue. Expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by or according to segll, S67314 amplicon(s) and S67314 segl lF and S67314 segllR primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No.
  • FABH HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues.
  • the expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non heart tissue sample Nos. 1-11,13-21,23-26,28-43, 47-74, 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: S67314 segl lF forward primer; and S67314 segl IR 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: S67314 segl l.
  • S67314 segl lF (SEQ ID NO:61): TCCCCTGAGAGCTGTAGAAGCT S67314 segl IR (SEQ ID NO:62): CGGCCTGTGTGAGTCCAAA S67314 segl 1(SEQ ID NO:63):
  • FIG. 5B is a histogram showing specific expression of the above -indicated FABH_HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 5B, the expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non-heart tissue sample Nos. 1-9, 11-21, 23-26, 28-43, 47-74 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: S67314 segl5F forward primer; and S67314 segl5R 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: S67314 segl5.
  • FIG. 44-46 Table 1, above
  • Figure 6 is a histogram showing relative expression of the above-indicated FABH_HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 6, the expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in the other samples (Sample Nos. 44-46 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: S67314seg4F forward primer; and S67314seg4R 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: S67314seg4.
  • Cluster N56180 features 7 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
  • Calsequestrin is a high- capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. The release of calcium bound to calsequestrin through a calcium release channel triggers muscle contraction.
  • the protein binds 40 to 50 moles of calcium.
  • 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/proj ects/LocusLink/>.
  • the heart- selective diagnostic marker prediction engine provided the following results with regard to cluster N56180. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods.
  • the numbers on the y-axis of Figure 7 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).
  • the histogram in Figure 7 concerning the number of heart-specific clones in libraries/sequences; as well as with regard to the histogram in Figure 8, concerning the actual expression of oligonucleotides in various tissues, including heart.
  • This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs was found to be 11; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs was found to be 2.4; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 4.70E-14.
  • One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non- heart ESTs as described above.
  • cluster N56180 features 7 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Calsequestrin, cardiac muscle isoform precursor. A description of each variant protein according to the present invention is now provided.
  • Variant protein N56180_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T1. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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:
  • N56180_P2 and CAQ2_HUMAN l.An isolated chimeric polypeptide encoding for N56180_P2, comprising a first amino acid sequence being at least 90 % homologous to MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEP VSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYIL KGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAFERIEDYIKLIGFFKSEDSEYY KAFEEAAEHFQPYIKFFATFDKGV conesponding to amino acids 1 - 203 of CAQ2 HUMAN, which also co ⁇ esponds to amino acids 1 - 203 of N56180_P2, and a second amino acid sequence being at least 70%>, optionally at least 80%, preferably at least 85%, more preferably at least
  • N56180_P2 An isolated polypeptide encoding for a tail of N56180_P2, 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 LWLTPVIPTLWEADGGGLHEPWSWRPAWATWLQRNYL in N56180JP2.
  • 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 or localized in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein.
  • 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 N56180_P2 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 N56180_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • SNPs Single Nucleotide Polymorphisms
  • Variant protein N56180JP2 is encoded by the following transcript(s): N56180_T1, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript N56180_T1 is shown in bold; this coding portion starts at position 242 and ends at position 961.
  • 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 N56180_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P4 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T3. An alignment is given to the l ⁇ iown protein (Calsequestrin, cardiac muscle isoform 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.
  • Comparison report between N56180_P4 and CAQ2_HUMAN l.An isolated chimeric polypeptide encoding for N56180_P4, comprising a first amino acid sequence being at least 90 % homologous to MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEP VSSDKVTQKQFQLKEIVLE co ⁇ esponding to amino acids 1 - 78 of CAQ2JTUMAN, which also co ⁇ esponds to amino acids 1 - 78 of N56180_P4, 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 HWQISQWWLHFQTPREEGKMKLLELSESADGAAWKRWGGNSNT
  • N56180_P4 An isolated polypeptide encoding for an edge portion of N56180_P4, 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 HWQISQWWLHFQTPREEGKMKLLELSESADGAAWKRWGGNSNTHRIQ, co ⁇ esponding to N56180_P4.
  • the location of the variant protein was detennined 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 or localized in the sarcoplasmic reticulum's terminal cistemae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein.
  • the protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protem has a signal peptide, and neither trans -membrane region prediction program predicts that this protein has a trans- membrane region..
  • Variant protein N56180_P4 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 N56180_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 9 - Amino acid mutations
  • Variant protein N56180_P4 is encoded by the following transcript(s): N56180_T3, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript N56180_T3 is shown in bold; this coding portion starts at position 242 and ends at position 1579.
  • 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 N56180_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P5 has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) N56180 T4.
  • An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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 N56180_P5 and CAQ2 HUMAN: l.An isolated chimeric polypeptide encoding for N56180_P5, comprising a first amino acid sequence being at least 90 % homologous to
  • chimeric polypeptide encoding for an edge portion of N56180_P5, 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 DV, having a structure as follows: a sequence starting from any of amino acid numbers 140-x to 140; and ending at any of amino acid numbers 141+ ((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 or localized in the sarcoplasmic reticulum's terminal cistemae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein.
  • 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 N56180_P5 also has the following non- silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 N56180_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 11 - Amino acid mutations Single Nucleotide Polymo ⁇ hisms
  • Variant protein N56180 P5 B encoded by the following transcript(s): N56180_T4, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript N56180_T4 is shown in bold; this coding portion starts at position 242 and ends at position 1252.
  • 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 N56180_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180_T5. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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.
  • Comparison report between N56180_P6 and CAQ2_HUMAN l.An isolated chimeric polypeptide encoding for N56180_P6, 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 NETEAEQSYV co ⁇ esponding to amino acids 1 - 10 of N56180_P6, second amino acid sequence being at least 90 % homologous to RAEEGLNFPTYDGKDRWSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEI VLELVAQVLEFIKAJGFVMVDAKKEAKLAKKL co ⁇ esponding to amino acids 18 - 106 of CAQ2_HUMAN, which also co ⁇ esponds to amino acids 11 - 99
  • polypeptide encoding for a head of N56180_P6, 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 NETEAEQSYV of N56180_P6.
  • N56180_P6 3.An isolated polypeptide encoding for an edge portion of N56180_P6, 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 LDY having a structure as follows (numbering according to N56180_P6): a sequence starting from any of amino acid numbers 99-x to 99; and ending at any of amino acid numbers 101 + ((n-2) - x), in which x varies from 0 to n-2.
  • Variant protein N56180_P6 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 N56180_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 13 -Amino acid mutations Single Nucleotide Polymo ⁇ hisms
  • Variant protein N56180_P6 is encoded by the following transcript(s): N56180_T5, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript N56180_T5 is shown in bold; this coding portion starts at position 1 and ends at position 964.
  • 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 N56180_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P7 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T6.
  • An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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.
  • Comparison report between N56180_P7 and CAQ2JHUMAN l.An isolated chimeric polypeptide encoding for N56180_P7, 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 MSSWLSAGSPSSLSV co ⁇ esponding to amino acids 1 - 15 of N56180_P7, and a second amino acid sequence being at least 90 % homologous to
  • DDDNSDEEDNDDSDDDDDE co ⁇ esponding to amino acids 203 - 399 of CAQ2_HUMAN, which also co ⁇ esponds to amino acids 16 - 212 of N56180_P7, wherein said first and second amino acid sequences 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: intracellularly.
  • the protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans -membrane region for this protein.
  • both signal-peptide prediction programs predict that this protein is a non-secreted protein..
  • Variant protein N56180_P7 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 N56180_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P7 is encoded by the following transcript(s): N56180_T6, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript N56180_T6 is shown in bold; this coding portion starts at position 71 and ends at position 706.
  • 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 N56180_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P8 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180_T7.
  • An alignment is given to the known protein (Calsequestrin, cardiac muscle isofonn 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:
  • N56180JP8 Comparison report between N56180JP8 and CAQ2JHUMAN: l.An isolated chimeric polypeptide encoding for N56180_P8, 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 MCRGYSTLLNPVS conesponding to amino acids 1 - 13 of N56180_P8, and a second amino acid sequence being at least 90 % > homologous to DGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTD ADSVWMEIPDDDDLPTAEELEDWIEDVLSGKLNTEDDDEDDDDDDNSDEEDNDDSDD DDDE co ⁇ esponding to amino acids 280 - 399 of CAQ2JHUMAN, which also co ⁇ esponds to amino acids 14 - 133 of N56
  • polypeptide encoding for a head of N56180_P8, 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 MCRGYSTLLNPVS of N56180_P8.
  • variant protein N56180_P8 is encoded by the following transcript(s): N56180_T7, for which the sequence(s) is/are given at the end ofthe application. The coding portion of transcript N56180 T7 is shown in bold; this coding portion starts at position 97 and ends at position 495.
  • 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 N56180_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 17 - Nucleic acid SNPs are 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 N56180_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein N56180_P9 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T8.
  • An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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:
  • An isolated polypeptide encoding for a tail of N56180_P9 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 SRNWTQ in N56180_P9.
  • 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 or localized in the sarcoplasmic reticulum's terminal cistemae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein.
  • the protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protem has a signal peptide, and neither trans -membrane region prediction program predicts that this protein has a trans- membrane region..
  • Variant protein N56180_P9 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 N56180JP9 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 18 -Amino acid mutations Single Nucleotide Polymo ⁇ hisms
  • Variant protein N56180_P9 is encoded by the following transcript(s): N56180_T8, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript N56180_T8 is shown in bold; this coding portion starts at position 242 and ends at position 997.
  • 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 l ⁇ iown or not; the presence of known SNPs in variant protein N56180_P9 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • cluster N56180 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 N56180_node_2 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): N56180_T1, N56180_T3, N56180 T4 and N56180JT8. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
  • Segment cluster N56180_node_20 is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T1, N56180JT3, N56180 T4, N56180 T5, N56180_T6 and N56180_T8. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
  • Segment cluster N56180_node_22 is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T8. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
  • Segment cluster N56180_node_28 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T7. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position [ Segment ending position N56180 T7 1 136
  • Segment cluster N56180_node_34 is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180 T3, N56180 T4, N56180_T5, N56180 T6 and N56180_T7. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts
  • Segment cluster N56180_node_36 is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T1, N56180JT3, N56180 T4, N56180 T5, N56180 T6 and N56180_T7. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts
  • Segment cluster N56180_node_4 is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180 T3, N56180 T4, N56180 T5 and N56180_T8. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts
  • Segment cluster N56180_node_6 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T3. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts
  • 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 N56180_node_0 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T5. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts
  • Segment cluster N56180_node_ 10 is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180 T1, N56180JT3, N56180 T4 and N56180_T8. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts
  • Segment cluster N56180_node__12 is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180JT3 and N56180_T8. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts
  • Segment cluster N56180_node_14 is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180_T3, N56180_T5 and N56180_T8. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts
  • Segment cluster N56180_node_16 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts
  • Segment cluster N56180_node_18 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T6. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts
  • Segment cluster N56180_node_24 is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180 T3, N56180 T4, N56180 T5 and N56180_T6. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts
  • Segment cluster N56180_node_26 is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180 T3, N56180 T4, N56180_T5 and N56180 T6. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts
  • Segment cluster N56180_node_29 is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180JT3, N56180JT4, N56180 T5, N56180 T6 and N56180 I7. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts
  • Segment cluster N56180_node_3 is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180 T3, N56180JT4 and N56180_T8. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts
  • Segment cluster N56180_node_31 is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180_T3, N56180_T4, N56180_T5, N56180_T6 and N56180_T7. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts
  • Segment cluster N56180_node_33 is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180 T3, N56180 T4, N56180JT5, N56180_T6 and N56180_T7. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts
  • Segment cluster N56180_node_35 can be found in the following transcript(s): N56180 T1, N56180 T3, N56180 T4, N56180JT5, N56180 T6 and N56180_T7. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts
  • Segment cluster N56180_node_8 is supported by 25 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180_T3, N56180 T4, N56180_T5 and N56180_T8. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts
  • Alignment segment 1/1 Quality: 3202.00 Escore: 0 Matching length: 337 Total length: 399 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 84.46 Total Percent Identity: 84.46 Gaps : 1
  • Alignment segment 1/1 Quality: 2955.00 Escore: 0 Matching length: 314 Total length: 385 Matching Percent Similarity: 99.04 Matching Percent Identity: 99.04 Total Percent Similarity: 80.78 Total Percent Identity: 80.78 Gaps : 1
  • Alignment segment 1/1 Quality: 1959.00 Escore: 0
  • cardiac muscle isofo ⁇ n transcripts which are detectable by amplicon as depicted in sequence name N56180 specifically in heart tissue
  • cardiac muscle isofo ⁇ n transcripts detectable by or according to seg6, N56180 amplicon(s) and N56180 seg6F and N56180 seg6R primers was measured by real time PCR.
  • 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: N56180 seg6F forward primer; and N56180 seg ⁇ R 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: N56180 seg6.
  • N56180 seg6F (SEQ ID NO:279): ATATCCCAGTGGTGGTTGCATT N56180 seg6R (SEQ ID NO:280): CCCTCCCCAGCGTTTCC N56180 seg6 (SEQ ID NO:335):
  • Calsequestrin cardiac muscle isoform transcripts detectable by or according to seg node(s), N56180 amplicon(s) and N56180 seg F and N56180 seg R primers was measured by real time PCR.
  • FIG. 10 is a histogram showing specific expression of the above -indicated Calsequestrin, cardiac muscle isoform transcripts in heart tissue samples as opposed to other tissues.
  • 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: N56180 seg .
  • N56180 seg F SEQ ID NO:336): TTGATACCACTTAGTGTAGCTCCAGC N56180 seg R (SEQ ID NO:337): TCAAGTAGTTGCTACAGACGCCA N56180 seg (SEQ ID NO:361): TTGATACCACTTAGTGTAGCTCCAGCATGGATCAGCAAACTTTTTCTGTAAAGAACA AAATGGTAAATATTTCAGGTTCTGTGGGCCAGATGGCGTCTGTAGCAACTACTTGA
  • the heart- selective diagnostic marker prediction engine provided the following results with regard to cluster T10377. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods.
  • the numbers on the y-axis of Figure 11 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 histogram in
  • Figure 11 concerning the number of heart- specific clones in libraries/sequences.
  • This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 10.9. The expression level of this gene in muscle was negligible; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 8.60E-15.
  • One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle.
  • cluster T10377 features 6 transcript(s), which were listed in Table 1 above.
  • T10377_P2 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10377_T1 and T10377_T2.
  • transcript(s) T10377_T1 and T10377_T2 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 protem according to the present invention to each such aligned protein is as follows:
  • T10377_P2 Comparison report between T10377_P2 and Q96NF5 (SEQ ID NO:362): 1.
  • An isolated polypeptide encoding for a head of T10377_P2 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 MEISLVKCSE of T10377_P2.
  • 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 intracellular because neither of the trans- membrane region prediction programs predicted a trans- membrane region for this protein.
  • variant protein T10377_P2 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 T10377_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • SNPs Single Nucleotide Polymo ⁇ hisms
  • Variant protein T10377_P2 is encoded by the following transcript(s): T10377_T1 and S T10377_T2, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript T10377_T1 is shown in bold; this coding portion starts at position 166 and ends at position 1518.
  • 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 T10377_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • transcript T10377_T2 The coding portion of transcript T10377_T2 is shown in bold; this coding portion starts at position 270 and ends at position 1622.
  • 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 l ⁇ iown or not; the presence of known SNPs in variant protein T10377_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein T10377_P5 has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) T10377 T5.
  • transcript(s) T10377 T5 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:
  • T10377_P5 Comparison report between T10377_P5 and Q96NF5: 1.
  • the location of the variant protein was detennined 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 one of the two signal- peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide..
  • Variant protein T10377_P5 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 T10377_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein T10377_P5 is encoded by the following transcript(s): T10377 T5, for which the sequence(s) is/are given at the end ofthe application.
  • the coding portion of transcript T10377_T5 is shown in bold; this coding portion starts at position 140 and ends at position 1453.
  • 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 T10377_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein T10377_P6 has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) T10377_T6.
  • transcript(s) T10377_T6 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:
  • T10377_P6 Comparison report between T10377_P6 and Q96NF5: 1.
  • 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 one of the two signal- peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide..
  • Variant protein T10377_P6 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 T10377_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein T10377_P6 is encoded by the following transcript(s): T10377 T6, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript T10377_T6 is shown in bold; this coding portion starts at position 140 and ends at position 1360.
  • 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 l ⁇ iown or not; the presence of known SNPs in variant protein T10377_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 11 - Nucleic acid SNPs given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is l ⁇ iown or not; the presence of known SNPs in variant protein T10377_P6 sequence provides support for the deduced sequence of this variant protein according
  • Variant protein T10377_P7 has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) T10377_T7.
  • transcript(s) T10377_T7 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 protem according to the present invention to each such aligned protein is as follows:
  • T10377_P7 Comparison report between T10377_P7 and Q96NF5: 1.
  • An isolated polypeptide encoding for a tail of T10377_P7 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 MSHELFSRFSLRLFGR in T10377_P7.
  • 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 one of the two signal- peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protem has a signal peptide..
  • Variant protein T10377_P7 also has the following non-silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 T10377_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein T10377_P7 is encoded by the following transcript(s): T10377_T7, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript T10377_T7 is shown in bold; this coding portion starts at position 140 and ends at position 1309.
  • 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 l ⁇ iown SNPs in variant protein T10377_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 13 - Nucleic acid SNPs 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 l ⁇ iown SNPs in variant protein T10377_P7 sequence provides support for the deduced sequence of this variant protein
  • Protein T10377_P8 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10377_T0.
  • transcript(s) T10377_T0 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 T10377_P8 and Q96NF5 An isolated chimeric polypeptide encoding for T10377_P8, comprising a first amino acid sequence being at least 90 % homologous to
  • YSQYEEKLQEEQRKHSAEKEALLEETNSFLK co ⁇ esponding to amino acids 1 - 261 of Q96NF5, which also co ⁇ esponds to amino acids 1 - 261 of T10377_P8, a second amino acid sequence comprising A, and a third amino acid sequence being at least 90 % homologous to IEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDK ERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKI SFLEGENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREINMPSRNYTPYTR VLELTMKKTLT co ⁇ esponding to amino acids 263 - 451 of Q96NF5, which also co ⁇ esponds to amino acids 263 - 451 of T10377_P8, wherein said first, second and third
  • the location of the protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs.
  • the protein is believed to be located as follows with regard to the cell: secreted.
  • the protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM: Signal peptide,NN:NO) predicts that this protein has a signal peptide..
  • Protein T10377_P8 also has the following non- silent SNPs (Single Nucleotide Polymo ⁇ hisms) 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 protein T10377_P8 sequence provides support for the deduced sequence of this protein according to the present invention).
  • SNPs Single Nucleotide Polymo ⁇ hisms
  • Protein T10377_P8 is encoded by the following transcript(s): T10377_T0, for which the sequence(s) is/are given at the end of the application
  • the coding portion of transcript T10377_T0 is shown in bold; this coding portion starts at position 140 and ends at position 1537.
  • 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 protein T10377_P8 sequence provides support for the deduced sequence of this protein according to the present invention).
  • cluster T 10377 features 18 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 T10377_node_0 according to the present favention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377 T0, T10377_T2, T10377_T5, T10377 T6 and T10377_T7. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
  • Segment cluster T10377_node_ 17 is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377_T2, T10377_T5, T10377 T6 and T10377_T7. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts
  • Segment cluster T10377_node_19 is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377 T2, T10377_T5, T10377_T6 and T10377_T7. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts
  • Segment cluster T10377_node_21 according to the present invention s supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377 T1, T10377_T2, T10377_T5, T10377_T6 and T10377_T7. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts
  • Segment cluster T10377_node_27 is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
  • Segment cluster T10377_node_33 is supported by 103 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377JTO, T10377_T1, T10377_T2, T10377_T5 and T10377_T6. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
  • 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 T10377_node_12 is supported by 35 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377JT2, T10377_T5, T10377_T6 and T10377_T7. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
  • Segment cluster T10377_node_14 is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377 T0, T10377JT1, T10377 T2, T10377JT5, T10377 T6 and T10377_T7. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts
  • Segment cluster T10377_node_16 can be found in the following transcript(s): T10377_T0, T10377 T1, T10377 T2, T10377JT5, T10377_T6 and T10377_T7.
  • Table 24 describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts
  • Segment cluster T10377_node_2 is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T1. Table 25 below describes the starting and ending position of this segment on each trans cript. Table 25 - Segment location on transcripts
  • Segment cluster T10377_node_23 is supported by 44 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377 T0, T10377 T1, T10377 T2, T10377_T5, T10377_T6 and T10377_T7. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts
  • Segment cluster T10377_node_25 is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377_T2, T10377JT5, T10377_T6 and T10377_T7. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts
  • Segment cluster T10377_node_29 is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377_T2 and T10377_T6. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts
  • Segment cluster T10377_node_3 is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T1 and T10377_T2. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts
  • Segment cluster T10377_node_31 is supported by 52 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377 T1, T10377_T2 and T10377 T5. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts
  • Segment cluster T10377_node_5 is supported by 30 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377JT2, T10377 T5, T10377_T6 and T10377_T7. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts
  • Segment cluster T10377_node_8 is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377 T2, T10377_T5, T10377 T6 and T10377_T7. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts
  • Segment cluster T10377_node_9 is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377JT0, T10377_T1, T10377 T2, T10377 T5, T10377_T6 and T10377_T7. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts
  • Alignment segment 1/1 Quality: 3642.00 Escore: 0 Matching length: 376 Total length: 376 Matching Percent Similarity: 99.47 Matching Percent Identity: 99.47 Total Percent Similarity: 99.47 Total Percent Identity: 99.47 Gaps :
  • Q96NF5 transcripts which are detectable by amplicon as depicted in sequence name T10377 specifically in heart tissue. Expression of Q96NF5 transcripts detectable by or according to junc25-31 node(s),
  • T10377 amplicon(s) and T10377 junc25-31F and T10377 junc25-31R primers was measured by real time PCR.
  • FIG. 12 is a histogram showing specific expression of the above- indicated Q96NF5 transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 12, the expression of Q96NF5 transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non- heart tissue sample Nos.
  • Primer pahs 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: T10377 junc25-31F forward primer; and T10377 junc25-31R 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: T10377 junc25- 31.
  • T10377 junc25-31F (SEQ ID NO:363): AGCAGATGGTCGAGGAGAATAATG T10377 junc25-31R (SEQ ID NO:364): ATCTCTCTGGTTTCCACTTCGG T10377 junc25-31 (SEQ ID NO:365):
  • FIG. 13 is a histogram showing specific expression of the above-indicated Q96NF5 transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 13, the expression of Q96NF5 transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non-heart tissue sample Nos.
  • Primer pahs 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: T10377 junc29-33F forward primer; and T10377 junc29-33R 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: T10377 junc29- 33.
  • T10377 junc29-33F (SEQ ID NO:366): CTTTCTTAGAAGGAGAGCCAAACAG T10377 junc29-33R (SEQ ID NO:367): CCTAAGTCAGAGTTTTCTTCATGGTTAAC T10377 junc29-33 (SEQ ID NO:368):
  • FIG. 14 is a histogram showing specific expression of the above-indicated Q96NF5 transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 14, the expression of Q96NF5 transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in the skeletal muscle (non-heart tissue sample Nos. 1-9,13-26,28-43,47-74 Table 1, "Tissue samples in testing 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: T10377 seg2-3F forward primer; and T10377 seg2-3R reverse primer.
  • the present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pah; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: T10377 seg2-3.
  • T10377 seg2-3F (SEQ ID NO:369): CTTCGCATTGTGCATAACACAA T10377 seg2-3R (SEQ ID NO:370): GAAACTCGGATACACAATCTCCAGA T10377 seg2-3 (SEQ ID NO:371): CTTCGCATTGTGCATAACACAAGCCCTGAACCAGCTGCTTTGGGAACCCCTGGGAA TAAAGTGCCCTACCTGCCTTTCAGGCACTGCCAAGCCTGGGGCATCTCTGGAGATTG TGTATCCGAGTTTC
  • Cluster Z24874 features 2 transcript(s) and 10 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
  • the heart- selective diagnostic marker prediction engine provided the following results with regard to cluster Z24874. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods.
  • the numbers on the y-axis of Figure 15 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).
  • the histogram in Figure 15 concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figure 16, concerning the actual expression of oligonucleotides in various tissues, including heart.
  • This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression ofthe cluster in non-heart ESTs, which was found to be 16.7; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 2.1; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 3.20E-09.
  • One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle.
  • This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 2.1, which clearly supports specific expression in heart tissue.
  • variant protein Z24874_PEA_2_P5 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s)
  • polypeptide encoding for a tail of Z24874_PEA_2_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%o, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LPGRHEVPRGALP in Z24874_PEA_2_P5.
  • Comparison report between Z24874_PEA_2_P5 and Q9NZK3 l.An isolated chimeric polypeptide encoding for Z24874_PEA_2_P5, comprising a first amino acid sequence being at least 90 % homologous to MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLE SLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSYKP co ⁇ esponding to amino acids 1 - 109 of Q9NZK3, which also co ⁇ esponds to amino acids 1 - 109 of Z24874_PEA_2_P5, 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
  • 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.
  • both signal-peptide prediction programs predict that this protein is a non- secreted protein..
  • Variant protein Z24874_PEA_2_P5 is encoded by the following transcript(s): Z24874_PEA_2_T10, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript Z24874JPEA_2_T10 is shown in bold; this coding portion starts at position 292 and ends at position 726.
  • 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 Z24874_PEA_2_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Variant protein Z24874_PEA_2_P6 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z24874_PEA_2_T11.
  • transcript(s) Z24874_PEA_2_T11 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:
  • polypeptide encoding for a tail of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP in Z24874_PEA_2_P6.
  • Comparison report between Z24874_PEA_2_P6 and Q9NZK3 l.An isolated chimeric polypeptide encoding for Z24874_PEA_2_P6, comprising a first amino acid sequence being at least 90 % homologous to MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLE SLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSY conesponding to amino acids 1 - 107 of Q9NZK3, which also co ⁇ esponds to amino acids 1 - 107 of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP co ⁇ esponding to amino acids
  • nucleic acid sequence encoding for a tail of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP in Z24874_PEA_2_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: 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.
  • Variant protein Z24874_PEA_2_P6 is encoded by the following transcript(s): Z24874_PEA_2_T11, for which the sequence(s) is/are given at the end of the application.
  • the coding portion of transcript Z24874_PEA_2_T11 is shown in bold; this coding portion starts at position 292 and ends at position 654.
  • 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 Z24874_PEA_2_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention).
  • Table 5 - Nucleic acid SNPs are 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 Z24874_PEA_2_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention.
  • cluster Z24874 features 10 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 Z24874_PEA_2_node_21 is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 6 below describes the starting and ending position of this segment on each transcript. Table 6 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_4 is supported by 19 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 7 below describes the starting and ending position of this segment on each transcript. Table 7 - Segment location on transcripts
  • 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 Z24874_PEA_2_node_0 is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 8 below describes the starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_10 is supported by 25 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_12 is supported by 26 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_13 is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_14 is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_16 is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_3 is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts
  • Segment cluster Z24874_PEA_2_node_6 is supported by 23 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts

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Abstract

Novel markers for cardiac disease that are both sensitive and accurate. These markers are differentially and/or specifically expressed in cardiac tissue, as opposed to other types of tissues, optionally and preferably including muscle 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 cardiac disease, including pathology and/or damage, including acute and/or chronic damage. The markets of the present invention, alone or in combination, show a high degree of differential detection between cardiac disease states and non-cardiac disease states.

Description

NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS OF CARDIAC DISEASE
FIELD OF THE INVENTION The present invention is related to novel nucleotide and protein sequences that are diagnostic markers for cardiac disease and/or pathological conditions, including cardiac damage, and assays and methods of use thereof.
BACKGROUND OF THE INVENTION Cardiovascular diseases are an important cause of mortality and morbidity. Amongst all age groups considered, IHD is the most common cause of death not only in men but also in women. Coronary atherosclerosis is a chronic progressing process, associated with angina type symptoms and frequently result in Acute Myocardial Infarction (AMI). The diagnosis is achieved with a combination of patient physical examination, ECG since 1950's molecular markers play the most important role in the differential diagnosis of AMI from other conditions with similar symptoms. Early diagnosis is mandatory of the establishment of early treatment (including blood diluting agents, thrombolysis, catheterization and surgery). Early molecular markers for AMI were SGOT and LDH were proved to be of very low specificity and are hardly being used at present. These markers were replaced by CPK, and later on by the heart specific CPK-MB variant. Its specificity is better than for SGOT and LDH, it is still limited both in specificity and sensitivity which reach only 67% when used together with electrocardiogram. In addition, cardiac surgery, myocarditis, and electrical cardioversion often result in elevated serum levels ofthe CPK-MB isoenryme. Small infarct with minor myocardial cell necrosis often do not increase serum CPK-MB to a detected level. Myoglobin is another heart damage low molecular (17kD) protem but is even less specific to heart muscle compared with CPK-MB. Its advantage over CPK-MB is a rapid rise from the onset of symptoms - usually between 3-6 hours. It is considered one of the earliest indicators (together with H- FABP) but it lacks specificity due to significant expression in skeletal muscle - its concentration is approximately two -fold lower in cardiac than skeletal muscle and the leads to seriously diminished specificity. Cardiac troponins are currently the routine serum cardiac markers used for the diagnosis of AMI. Troponin-I and Troponin-T have amino acid sequences different from those of the skeletal muscle called cTnT and cTnl (cardiac Troponin-T and I recpectively). Cardiac troponins are not found in the serum of healthy individuals and rise to up to 20 times above a predefined cut-off level, therefore are very useful and sensitive in the detection of cardiac damage. They are capable of detecting very small cardiac damage - micro- infarction, it is associated with a very adverse longer term prognosis. Cardiac troponin's sensitivity is considerably higher than CPK-MB but they suffer from a few disadvantages: 1. They are not early markers - cTnl and cTnT reach peak serum value in about 12 and 48 hours respectively after symptoms onset. 2. Levels of cTnl and cTnT remain elevated for up to 10 days and 14 days respectively after AMI, therefore cannot be used for the detection of re- infarction. 3. Other heart diseases such as Congestive Heart Failure and Myocarditis can increase troponins concentrations in the serum. The lack of specificity for AMI is an advantage when there are other supporting clinical evidence directing the doctor towards another diagnosis. Troponins might have a diagnostic value in assessing myocardial damage after coronary artery perfusion, monitoring progression and prognosis of unstable angina, in the detection and prognosis of cardiac contusion after blunt trauma, detecting myocarditis. The heart specific variant H-FABP (Heart Fatty Acid binding protein) is a low molecular protein (15Kd) soluble non- enzyme protein. H-FABP concentration in the heart muscle is greater than that in skeletal muscle, and its normal baseline concentration is several fold lower than myoglobin. In addition, it reaches peak value in the urine and blood early, within 2-3 hours from AMI. Within a period of 30-210 minutes after symptoms started, HFABP has higher sensitivity - up to 80% - when compared with other cardiac markers (CPK-MB and the troponins sensitivity were reported to be 64% in the first 6 hours after AMI). Yet, H-FABP still misses every 5fh patient in this time scale. H-FABP has other limitations as well, including 1. rising in the plasma after exercise 2. released from muscle in skeletal damage during the course of AMI (like from intramuscular injections) 3. reduced clearance in renal failure situations. The search for novel cardiac damage markers is ongoing. Other proteins are under trials for that purpose including glycogen phosphorylase BB, HIF and VEGF 21. SUMMARY OF THE INVENTION Markers for the cardiac disease and/or cardiac pathology, including but not limited to cardiac damage in the prior art are not sufficiently sensitive and/or accurate, alone or in combination. The present invention overcomes these deficiencies of the background art by providing novel markers for cardiac disease and/or cardiac pathology, including but not limited to cardiac damage that are both sensitive and accurate. Optionally and preferably, these markers are detected in a biological sample. According to preferred embodiments of the present invention, cardiac disease and/or pathology and/or condition and/or disorder may comprise one or more of Myocardial infarct, acute coronary syndrome, angina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure or any type of heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, assessing the size of infarct in Myocardial infarct, the differential diagnosis of heart related conditions from lung related conditions (as pulmonary embolism), the differential diagnosis of Dyspnea, and cardiac valves related conditions. According to preferred embodiments of the present invention, examples of suitable biological samples include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, and any human organ or tissue. In a preferred embodiment, the biological sample comprises cardiac tissue and/or a serum sample and/or a urine sample and/or any other tissue or liquid sample. The sample can optionally be diluted with a suitable eluant before contacting the sample to the antibody. 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/TMFJMM/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 B informatics, 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.V/www.cbs.dtu.dk/services/SignalP/background/prediction.php) for signal peptide prediction. The terms "signalpjimm" 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 detennined 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=blosuml00 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, CA, USA (see for example data regarding the Human Genome U133 (HG-U133) Set at www.affymeftix.com products/arrays/specific/hgul33.affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.com/products/arrays/specific/hgul33av2.affx; and Human Genome U133 Plus 2.0 Array at www.affymetrix.com/products/arrays/specific/hgul33plus.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. 1 207-210). The dataset (including results) is available from www.ncbi.nlm.nih.gov/geo/query/acc. cgi?acc=GSEl 133 for the Series GSE1133 database (published on March 2004); a reference to these results is as follows: Su et al (Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7. Epub 2004 Apr 09). Oligonucleotide probes for use with arrays designed by the present inventors: >S67314_0_0_741 (SEQ ID NO 392)
CACAGAGCCAGGATGTTCTTCTGACCTCAGTATCTACTCCAGCTCCAGCT >S67314_0_0_744 (SEQ ID NO 393) TGGCATGCTGGAACATGGACTCTAGCTAGCAAGAAGGGCTCAAGGAGGTG
In the heart specific clusters, a first set of abbreviations is used for the first histogram
ADP = adipocyte
BLD = blood
BLDR = bladder BRN = brain
BONE = bone
BM = bone marrow
BRS = mammary gland
CAR = cartilage CNS = central nervous system
COL = colon
E-ADR = endocrine_adrenal_gland
E-PAN = endocrine_pancreas
E-PT = endocrine_parathyroid_thyroid ENDO = endocrine_unchar
EPID = epididymis GI = gastrointestinal tract
GU = genitourinary
HN = head and neck
HRT = heart KD = kidney
LI = liver
LUNG = lung
LN = lymph node
MUS = muscle OV = ovary
PNS = peripheral nervous system
PRO = prostate
SKIN = skin
SPL = spleen SYN = synovial membrane
TCELL = immune T cells
THYM = thymus
TST = testes
UTER = cervix- uterus VAS = vascular
In the second histogram(s) of the heart paragraph, the oligo-probe names are abbreviated/enumerated as follows:
"adipocyte", "Al"; "adrenalcortex", "A2"; "adrenalgland", "A3"; "amygdala", "A4"; "appendix", "A5"; "atrioventricularnode", "A6"; "bm_cdl 05_endothelial", "El"; "bm_cd33_myeloid", "Ml";
"bm_cd34_", "Bl";
"bm_cd7 l_earlyerythroid", "El";
"bonemarrow", "B2";
"bronchialepithehalcells", "B3";
"cardiacmyocytes", "Cl";
"caudatenucleus", "C2";
"cerebellum", "C3";
"cerebellumpeduncles", "C4";
"ciliaryganglion", "C5";
"cingulatecortex", "C6";
"globuspallidus", "GI";
"heart", "HI";
"hypothalamus", "H2";
"kidney", "Kl";
"liver", "Ll";
"lung", "L2";
"lymphnode", "L3";
"medullaoblongata", "Ml";
"occipitallobe", "01";
"olfactorybulb", "02";
"ovary", "03";
"pancreas", "PI";
"pancreaticislets", "P2";
"parietallobe", "P3";
"pb_bdca4_dentritic_cells", "P4";
"pb_cdl4_monocytes", "P5";
"pb_cdl9_bcells", "P6";
"pb_cd4_tcells", "P7";
"pb_cd56_nkcells", "P8";
"ρb_cd8_tcells", "P9"; "pituitary", "Pa";
"placenta", "Pb";
"pons", "Pc";
"prefrontalcortex", "Pd";
"prostate", "Pe";
"salivarygland", "SI";
"skeletalmuscle", "S2";
"skin", "S3";
"smoothmuscle", "S4";
"spinalcord", "S5";
"subthalamicnucleus", "S6";
"superiorcervicalganglion", "S7";
"temporallobe", "TI";
"testis", "T2";
"testisgermcell", "T3";
"testisinterstitial", "T4";
"testisleydigcell", "T5";
"testisseminiferoustubule" , "S6";
"thalamus", "T7";
"thymus", "T8";
"thyroid", "T9";
"tonsil", "Ta";
"trachea", "Tb";
"trigeminalganglion", "Tc";
"uterus", "Ul";
"uteruscorpus", "U2";
"wholeblood", "Wl";
"wholebrain", "W2";
It should be noted that the terms "segment", "seg" and "node" are used interchangeablyence 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 ohgonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary ohgonucleotides may optionally be derived, and/or for any other use. As used herein the phrase "cardiac disease" includes any type of cardiac pathology and/or disorder and/or damage, including both chronic and acute damage, as well as progression from acute to chronic damage of the heart, and also propagation of one acute event to another acute event. An example of the latter may occur when an infarct is followed by another infarct in a relatively short period of time, such as within 24 hours for example. An infarct may also lead to acute heart failure immediately after the infarct, as another example. These non- limiting examples are intended to demonstrate that cardiac disease may also comprise a plurality of acute events. The term "marker" in the context of the present invention lefers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from patients having a cardiac disease, such as acute cardiac damage for example, as compared to a comparable sample taken from subjects who do not have cardiac disease. As used herein the phrase "differentially present" refers to differences in the quantity of a marker present in a sample talcen from patients having cardiac disease as compared to a comparable sample taken from patients who do not have cardiac disease. 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. For example, in the case of acute cardiac damage, it is possible that a marker (such as a protein or fragment thereof) could optionally be present in a blood sample from the patient, indicating the presence of damage; lack of presence of such a marker (and/or presence at a low level) would therefore optionally and preferably indicate a lack of such damage. Alternatively, chronically damaged heart might cause a low level of the marker to be present in the blood sample, while acute damage would cause a high level to be present. One of ordinary skill in the art could easily detennine such relative levels of the markers; further guidance is provided in the description of each individual marker below.
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 ofthe disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery. The term "detecting" may also optionally encompass any ofthe 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 ofthe 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 ofthe 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, ofthe variant as opposed to the normal tissues. A "test amount" of a marker refers to an amount of a marker present in a sample being tested. A test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals). 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 cardiac disease. 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 cardiac disease or a person without cardiac disease. 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. Fahr lander 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 ofthe 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 protem 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 biologies. 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 protem 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 a isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID
NOs: 1, 2, 3 and 4. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID
NOs: 65, 66, 67, 68, 69, 70, 71 and 72. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 281, 282, 283 and 284. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID
NOs: 5, 6, 7, 8, 9 and 10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID
NOs: 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93 and 94 . According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID
NOs: 285, 286, 287, 288, 289, 290 and 291 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 12, 13, 14, 15, 16 and 17 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 292, 293, 294, 295 and 296 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 18 and 19. According to preferred embodiments of the present invention, there is provided ai isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 113, 114, 115, 116, 117, 118, 119, 120, 121 and 122. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 297 and 298. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 20 and 21. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 123, 124, 125, 126, 127, 128 and 129. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 299 and 300. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 26, 27, 28, 29 and 30. According to preferred embodiments of the present invention, there is provided ati isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162 and 163. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 305; 306; 307 and 308 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 31, 32, 33, 34, 35, 36 and 37. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185 and 186 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 309, 310, 311 and 312. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 38, 39, 40 and 41. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 187, 188, 189, 190, 191, 192, 193, 194, 195 and 196. According to preferred embodiments of the present invention, there is provided ε isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 313, 314, 315 and 316. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 42, 43, 44, 45, 46, 47, 48, 49 and 50. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207 and 208. π According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant SELECTED FROM THE GROUP
CONSISTING OF SEQ ID NOs: 317, 318, 319, 320, 321, 322, 323, 324 and 325. According to prefeπed embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs:51, 52, 53, 54, 55, 56, 57, 58, 59 and 60. According to prefeπed embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SELECTED FROM THE GROUP CONSISTING OF SEQ ID NOs: 209 to 273. According to prefened embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 326 to 334. According to prefeπed embodiments of the present invention, there is provided ai isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NOs: 22-25, 353 or 386. According to prefeπed embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 130-149. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 301-304, 325, 354-356 or 387. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 326, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 1855 of SEQ ID NO.338, which also coπesponds to amino acids 1 - 1855 of SEQ ID NO.326, 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 sequence corresponding to amino acids 1856 - 1904 of SEQ ID NO. 326, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 326, 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT in SEQ ID NO. 326. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 327, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 1326 of SEQ ID NO. 339, which also coπesponds to amino acids 1 - 1326 of SEQ ID NO. 327, 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 sequence coπesponding to amino acids 1327 - 1336 of SEQ ID NO. 327, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided ai isolated polypeptide encoding for a tail of SEQ ID NO. 327, 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 VRPSGEGGQA in SEQ ID NO. 327. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 328, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 1508 of SEQ ID NO. 339, which also coπesponds to amino acids 1 - 1508 of SEQ ID NO. 328, 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 sequence coπesponding to amino acids 1509 - 1534 of SEQ ID NO. 328, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 328, 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 GVLGVQEARDELVGGRAMQGQGEHRL in SEQ ID NO. 328. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 329, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 1763 of SEQ ID NO. 338, which also coπesponds to amino acids 1 - 1763 of SEQ ID NO. 329, 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 sequence coπesponding to amino acids 1764 - 1788 of SEQ ID NO. 329, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 329, 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 VSDRPPSASPKDRNKALGPGQATVL in SEQ ID NO. 329. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 330, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%o, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence coπesponding to amino acids 1 - 22 of SEQ ID NO. 330, and a second amino acid sequence being at least 90 % homologous to amino acids 528 - 1939 of SEQ ID NO. 340, which also coπesponds to amino acids 23 - 1434 of SEQ ID NO. 330, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 330, 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 MGLWKPGSVLSDSLFASSPCPQ of SEQ ID NO. 330. According to prefeπed embodiments of the present invention, there is provided ai isolated chimeric polypeptide encoding for SEQ ID NO. 331, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 527 of SEQ ID NO. 339, which also coπesponds to amino acids 1 - 527 of SEQ ID NO. 331, 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 sequence coπesponding to amino acids 528 - 555 of SEQ ID NO. 331, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 331, 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 VPPWPHHLCPLLCHPDKVVAESLLHPRN in SEQ ID NO. 331. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO.332, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 470 of SEQ ID NO.338, which also coπesponds to amino acids 1 - 470 of SEQ ID NO.332, a second amino acid sequence being at least 90 % homologous to amino acids 528 - 1855 of SEQ ID NO.338, which also coπesponds to amino acids 471 - 1798 of SEQ ID NO.332, 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 sequence coπesponding to amino acids 1799 - 1847 of SEQ ID NO.332, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO.332, 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 ainino 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 DP, having a structure as follows: a sequence starting from any of amino acid numbers 470-x to 470; and ending at any of amino acid numbers 471+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 332, 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT in SEQ ID NO.332. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric plypeptide encoding for SEQ ID N0.333, comprising a first amino acid sequence being at least 90 % homologous to amino acids 165 - 1939 of SEQ ID NO. 340, which also coπesponds to amino acids 1 - 1775 of SEQ ID NO.333. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO.334, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1165 - 1939 of SEQ ID NO. 340, which also coπesponds to amino acids 1 - 775 of SEQ ID N0.334-. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID N0.317, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 158 of SEQ ID NO. 341, which also coπesponds to amino acids 1 - 158 of SEQ ID N0.317. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID N0.318, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 156 of SEQ ID NO. 341, which also coπesponds to amino acids 1 - 156 of SEQ ID NO.318, 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 sequence coπesponding to amino acids 157 - 166 of SEQ ID NO.318, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO.318, 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
VSVGQECGSG in SEQ ID NO.318. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID N0.319, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 156 of SEQ ID NO. 341, which also coπesponds to amino acids 1 - 156 of SEQ ID NO.319, 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 sequence coπesponding to amino acids 157 - 210 of SEQ ID NO.319, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.
According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO.319, 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY in SEQ ID NO.319 . According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 320, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 60 of Q96NR4, which also coπesponds to amino acids 1 - 60 of SEQ ID NO. 320, 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 sequence coπesponding to amino acids 61 - 114 of SEQ ID NO. 320, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 320, 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 DGISSLCYSSLSKSLLSQPLRETSSALNDISLLQALMPLLGWTSHWTCITVGLY in SEQ ID NO. 320. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 320, comprising a first amino acid sequence being at least 90 % homologous to amino acids 97 - 156 of SEQ ID NO. 341, which also coπesponds to amino acids 1 - 60 of SEQ ID NO. 320, 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 sequence coπesponding to amino acids 61 - 114 of SEQ ID NO. 320, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 321, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 14 of SEQ ID NO. 342, which also coπesponds to amino acids 1 - 14 of SEQ ID NO. 321, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to coπesponding to amino acids 62 - 133 of SEQ ID NO. 342, which also corresponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 321, 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((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 SEQ ID NO. 321, 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 sequence coπesponding to amino acids 1 - 15 of SEQ ID NO. 321, and a second amino acid sequence being at least 90 % homologous to coπesponding to amino acids 39 - 110 of SEQ ID NO. 343, which also coπesponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 321, 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
MRGEHNSTSYDSAVS of SEQ ID NO. 321. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 321, comprising a first amino acid sequence being at least 90 %> homologous to coπesponding to amino acids 97 - 110 of SEQ ID
NO. 341, which also coπesponds to amino acids 1 - 14 of SEQ ID NO. 321, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to coπesponding to amino acids 158 - 229 of SEQ ID NO. 341, which also coπesponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 321, 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies
According to prefeπed embodiments of the present invention, there is provided ai isolated polypeptide encoding for a tail of SEQ ID NO. 320, 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY in SEQ ID NO. 320. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 321, comprising a first amino acid sequence being at least 90 % homologous to conesponding to amino acids 1 - 14 of SEQ ID NO. 342, which also coπesponds to amino acids 1 - 14 of SEQ ID NO. 321, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to coπesponding to amino acids 62 - 133 of SEQ ID NO. 342, which also coπesponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided ai isolated polypeptide encoding for an edge portion of SEQ ID NO. 321, 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321 : a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies from 0 to n-2. ; According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 321, 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 sequence corresponding to amino acids 1 - 15 of SEQ ID NO. 321, and a second amino acid sequence being at least 90 % homologous to coπesponding to amino acids 39 - 110 of SEQ ID NO. 343, which also coπesponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 321, 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 MRGEHNSTSYDSAVS of SEQ ID NO. 321. According to prefeπed embodiments of the present invention, there is provided ai isolated chimeric polypeptide encoding for SEQ ID NO. 321, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 97 - 110 of SEQ ID NO. 341, which also coπesponds to amino acids 1 - 14 of SEQ ID NO. 321, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to coπesponding to amino acids 158 - 229 of SEQ ID NO. 341, which also coπesponds to amino acids 16 - 87 of SEQ ID NO. 321, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 321, 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 VSI having a structure as follows (numbering according to SEQ ID NO. 321): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 322, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 62 of SEQ ID NO. 342, which also coπesponds to amino acids 1 - 62 of SEQ ID NO. 322. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 322., 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 sequence coπesponding to amino acids 1 - 23 of SEQ ID NO. 322., and a second amino acid sequence being at least 90 % homologous to conesponding to amino acids 1 - 39 of SEQ ID NO. 343., which also coπesponds to amino acids 24 - 62 of SEQ ID NO. 322., wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 322., 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 MRGEHNSTSYDSAVIYRGFWAVL of SEQ ID NO. 322.. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 322., comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 97 - 158 of SEQ ID NO. 341., which also coπesponds to amino acids 1 - 62 of SEQ ID NO. 322.. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 324, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 60 of SEQ ID NO. 342, which also coπesponds to amino acids 1 - 60 of SEQ ID NO. 324, 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 sequence coπesponding to amino acids 61 - 70 of SEQ ID NO. 324, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 324, 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 VSVGQECGSG in SEQ ID NO. 324. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 324, 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 sequence coπesponding to amino acids 1 - 23 of SEQ ID NO. 324, a second amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 37 of SEQ ID NO. 343, which also coπesponds to amino acids 24 - 60 of SEQ ID NO. 324, 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 coπesponding to amino acids 61 - 70 of SEQ ID NO. 324, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 324, 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 MRGEHNSTSYDSAVIYRGFWAVL of SEQ ID NO. 324. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 324, 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
VSVGQECGSG in SEQ ID NO. 324. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 324, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 97 - 156 of SEQ ID NO. 341, which also corresponds to amino acids 1 - 60 of SEQ ID NO. 324, 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 coπesponding to amino acids 61 - 70 of SEQ ID NO. 324, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided a isolated polypeptide encoding for a tail of SEQ ID NO. 324, comprising a polypeptide being at least 70%o, 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 VSVGQECGSG in SEQ ID NO. 324. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 313, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 115 of SEQ ID NO. 344, which also coπesponds to amino acids 1 - 115 of SEQ ID NO. 313, and a second amino acid sequence being at least 90 % homologous to coπesponding to amino acids 152 - 319 of SEQ ID NO. 344, which also coπesponds to amino acids 116 - 283 of SEQ ID NO. 313, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. Accordmg to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 313, 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 IY, having a structure as follows: a sequence starting from any of amino acid numbers 115-x to 115; and ending at any of amino acid numbers 116+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 313, of cluster Z36249 comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 -
70 of SEQ ID NO. 345, which also coπesponds to amino acids 1 - 70 of SEQ ID NO. 313, a bridging amino acid K coπesponding to amino acid 71 of SEQ ID NO. 313, a second amino acid sequence being at least 90 % homologous to coπesponding to amino acids 72 - 115 of SEQ ID NO. 345, which also coπesponds to amino acids 72 - 115 of SEQ ID NO. 313, and a third amino acid sequence being at least 90 %> homologous to coπesponding to amino acids 152 - 319 of SEQ ID NO. 345, which also coπesponds to amino acids 116 - 283 of SEQ ID NO. 313, 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 prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 314, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 184 of SEQ ID NO. 344, which also coπesponds to amino acids 1 - 184 of SEQ ID NO. 314, 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 sequence coπesponding to amino acids 185 - 197 of SEQ ID NO. 314, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 314, 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 VNIFLCLGMSQKK in SEQ ID NO. 314. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 314, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 70 of SEQ ID NO. 345, which also coπesponds to amino acids 1 - 70 of SEQ ID NO. 314, a bridging amino acid K coπesponding to amino acid 71 of SEQ ID NO. 314, a second amino acid sequence being at least 90 % homologous to coπesponding to amino acids 72 - 184 of SEQ ID NO. 345, which also coπesponds to amino acids 72 - 184 of SEQ ID NO. 314, 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 conesponding to amino acids 185 - 197 of SEQ ID NO. 314, 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 prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 314, 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 VNIFLCLGMSQKK in SEQ ID NO. 314. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 313, 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 IY, having a structure as follows: a sequence starting from any of amino acid numbers 115-x to 115; and ending at any of amino acid numbers 116+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 315, comprising a first amino acid sequence being at least 90 % homologous to coπesponding to amino acids 1 - 151 of SEQ ID NO. 344, which also coπesponds to amino acids 1 - 151 of SEQ ID NO. 315, 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 sequence coπesponding to amino acids 152 - 177 of SEQ ID NO. 315, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 315, 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 VRLMQSTAKSSSLILCFLCFTPVLLI in SEQ ID NO. 315. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 315, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 70 of SEQ ID NO. 345, which also coπesponds to amino acids 1 - 70 of SEQ ID NO. 315, a bridging amino acid K coπesponding to amino acid 71 of SEQ ID NO. 315, a second amino acid sequence being at least 90 % homologous to amino acids 72 - 151 of SEQ ID NO. 345, which also coπesponds to amino acids 72 - 151 of SEQ ID NO. 315, 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 sequence coπesponding to amino acids 152 - 177 of SEQ ID NO. 315, 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 prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 315, 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 VRLMQSTAKSSSLILCFLCFTPVLLI in SEQ ID NO. 315. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 316, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 151 of SEQ ID NO. 344, which also coπesponds to amino acids 1 - 151 of SEQ ID NO. 316, and a second amino acid sequence being at least 90 % homologous to amino acids 185 - 319 of SEQ ID NO. 344, which also coπesponds to amino acids 152 - 286 of SEQ ID NO. 316, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 316, comprising a polypeptide having a length "n", wherein nis 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 EL, having a structure as follows: a sequence starting from any of amino acid numbers 151-x to 151; and ending at any of amino acid numbers 152+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 316, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 70 of SEQ ID NO. 345, which also coπesponds to amino acids 1 - 70 of SEQ ID NO. 316, a bridging amino acid K conesponding to amino acid 71 of SEQ ID NO. 316, a second amino acid sequence being at least 90 % homologous to amino acids 72 - 151 of SEQ ID NO. 345, which also conesponds to amino acids 72 - 151 of SEQ ID NO. 316, and a third amino acid sequence being at least 90 % homologous to amino acids 185 - 319 of SEQ ID NO. 345, which also coπesponds to amino acids 152 - 286 of SEQ ID NO. 316, 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 prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 316, of cluster Z36249 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 EL, having a structure as follows: a sequence starting from any of amino acid numbers 151-x to 151; and ending at any of amino acid numbers 152+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 309, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 42 of SEQ ID NO. 346, which also coπesponds to amino acids 1 - 42 of SEQ ID NO. 309, a bridging amino acid N coπesponding to amino acid 43 of SEQ ID NO. 309, a second amino acid sequence being at least 90 % homologous to amino acids 44 - 657 of SEQ ID NO. 346, which also coπesponds to amino acids 44 - 657 of SEQ ID NO. 309, and a third amino acid sequence being at least 70%, optionally at least 80%o, preferably at least 85%, more preferably at least 90%> and most preferably at least 95%> homologous to a polypeptide sequence coπesponding to amino acids
658 - 708 of SEQ ID NO. 309, 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 prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 309, 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 VRPHLTLKAPLGLRMHRDPLRTPSPKSWPLTQPLTPDATLTPQAILTPTLT in SEQ ID NO. 309. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 310, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 42 of SEQ ID NO. 346, which also conesponds to amino acids 1 - 42 of SEQ ID NO. 310, a bridging amino acid N coπesponding to amino acid 43 of SEQ ID NO. 310, a second amino acid sequence being at least 90 % homologous to amino acids 44 - 676 of SEQ ID NO. 346, which also coπesponds to amino acids 44 - 676 of SEQ ID NO. 310, 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 sequence coπesponding to amino acids 677 - 685 of SEQ ID NO. 310, 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 prefeπed embodiments of the present invention, there is provided ai isolated polypeptide encoding for a tail of SEQ ID NO. 310, 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 EHGRGPGKT in SEQ ID NO. 310. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 311, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 42 of SEQ ID NO. 346, which also coπesponds to amino acids 1 - 42 of SEQ ID NO. 311, a bridging amino acid N coπesponding to amino acid 43 of SEQ ID NO. 311, a second amino acid sequence being at least 90 %> homologous to amino acids 44 - 657 of SEQ ID NO. 346, which also conesponds to amino acids 44 - 657 of SEQ ID NO. 311, 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 sequence coπesponding to amino acids 658 - 696 of SEQ ID NO. 311, 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 prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 311, 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 GPGRHAGNAGTLTQSLDCDAGVPPPAFQPLSTSYIYFSE in SEQ ID NO. 311. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 312, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 42 of SEQ ID NO. 346, which also coπesponds to amino acids 1 - 42 of SEQ ID NO. 312, a bridging amino acid N coπesponding to amino acid 43 of SEQ ID NO. 312, a second amino acid sequence being at least 90 % homologous to amino acids 44 - 610 of SEQ ID NO. 346, which also conesponds to amino acids 44 - 610 of SEQ ID NO. 312, 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 AMH coπesponding to amino acids 611 - 613 of SEQ ID NO. 312, 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 prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 305, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 381 of SEQ ID NO. 347, which also coπesponds to amino acids 1 - 381 of SEQ ID NO. 305, and a second amino acid sequence being at least 10%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence coπesponding to amino acids 382 - 387 of SEQ ID NO. 305, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 305, 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 TSLSLS in SEQ ID NO. 305. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 306, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 338 of SEQ ID NO. 347, which also coπesponds to amino acids 1 - 338 of SEQ ID NO. 306, 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 sequence coπesponding to amino acids 339 - 346 of SEQ ID NO. 306, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 306, 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 VLLCAQWP in SEQ ID NO. 306. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 307, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 223 of SEQ ID NO. 347, which also coπesponds to amino acids 1 - 223 of SEQ ID NO. 307, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90%o and most preferably at least 95%> homologous to a polypeptide having the sequence A coπesponding to amino acids 224 - 224 of SEQ ID NO. 307, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 308, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 294 of SEQ ID NO. 347, which also conesponds to amino acids 1 - 294 of SEQ ID NO. 308, 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 sequence conesponding to amino acids 295 - 304 of SEQ ID NO. 308, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 308, 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 RCYLRFLDIY in SEQ ID NO. 308. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 281, 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 amino acids 1 - 116 of FABH_HUMAN, which also coπesponds to amino acids 1 - 116 of 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% homobgous to a polypeptide sequence coπesponding to amino acids 117 - 215 of SEQ ID NO. 281, wherein said firstand second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRWSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL in SEQ ID NO. 281. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 281, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also conesponds to amino acids 1 - 116 of 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 sequence coπesponding to amino acids 117 - 215 of SEQ ID NO. 281, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL in SEQ ID NO. 281. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 282, 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 sequence coπesponding to amino acids 1 - 116 of FABH HUMAN, which also coπesponds to amino acids 1 - 116 of SEQ ID NO. 282, 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 sequence conesponding to amino acids 117 - 178 of SEQ ID NO. 282, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 282, comprismg 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 DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in SEQ ID NO. 282. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 282, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also coπesponds to amino acids 1 - 116 of SEQ ID NO. 282, 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%o homologous to a polypeptide sequence conesponding to amino acids 117 - 178 of SEQ ID NO. 282, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided ai isolated polypeptide encoding for a tail of SEQ ID NO. 282, 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 DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG According to prefened embodiments of the present invention, there is provided ai isolated chimeric polypeptide encoding for SEQ ID NO. 283, 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 amino acids 1 - 116 of FABHJHUMAN, which also conesponds to amino acids 1 - 116 of SEQ ID NO. 283, 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 sequence coπesponding to amino acids 117 - 126 of SEQ ID NO. 283, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 283, 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 MEKLQLRNVK in SEQ ID NO. 283. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 283, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also coπesponds to amino acids SEQ ID NO. 283, 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 sequence conesponding to amino acids 117 - 126 of SEQ ID NO. 283, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 283, comprising a polypeptide being at least 70%o, 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
MEKLQLRNVK in SEQ ID NO. 283. According to prefeπed embodiments of tie present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 284, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 24 of FABHJHUMAN, which also coπesponds to amino acids 1 - 24 of SEQ ID NO. 284, 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 sequence coπesponding to amino acids 25 - 35 of SEQ ID NO. 284, and a third amino acid sequence being at least 90 % homologous to amino acids 25 - 133 of FABH HUMAN, which also coπesponds to amino acids 36 - 144 of SEQ ID NO. 284, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 284, 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 AHILITFPLPS, coπesponding to SEQ ID NO. 284. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 284, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 24 of AAP35373, which also conesponds to amino acids 1 - 24 of SEQ ID NO. 284, 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 sequence coπesponding to amino acids 25 - 35 of SEQ ID NO. 284, and a third amino acid sequence being at least 90 % homologous to amino acids 25 - 133 of AAP35373, which also coπesponds to amino acids 36 - 144 of SEQ ID NO. 284, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 284, comprising an amino acid sequence being at least 10%, 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 AHILITFPLPS, coπesponding to SEQ ID NO. 284. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 285, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 203 of SEQ ID NO. 349, which also coπesponds to amino acids 1 - 203 of SEQ ID NO. 285, 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 sequence coπesponding to amino acids 204 - 240 of SEQ ID NO. 285, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided ai isolated polypeptide encoding for a tail of SEQ ID NO. 285, 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 LWLTPVIPTLWEADGGGLHEPWSWRPAWATWLQRNYL in SEQ ID NO. 285. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 286, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 78 of SEQ ID NO. 349, which also coπesponds to amino acids 1 - 78 of SEQ ID NO. 286, 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 sequence conesponding to amino acids 79 - 125 of SEQ ID NO. 286, and a third amino acid sequence being at least 90 % homologous to amino acids 79 - 399 of SEQ ID NO. 349, which also coπesponds to amino acids 126 - 446 of SEQ ID NO. 286, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 286, 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
HWQISQWWLHFQTPREEGKMKLLELSESADGAAWKRWGGNSNTHRIQ, conesponding to SEQ ID NO. 286. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 287, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 140 of SEQ ID NO. 349, which also coπesponds to amino acids 1 - 140 of SEQ ID NO. 287, and a second amino acid sequence being at least 90 % homologous to amino acids 203 - 399 of SEQ ID NO. 349, which also conesponds to amino acids 141 - 337 of SEQ ID NO. 287, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 287, 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 DV, having a structure as follows: a sequence starting from any of amino acid numbers 140-x to 140; and ending at any of amino acid numbers 141+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encodmg for SEQ ID NO. 288, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%o, more preferably at least 90%> and most preferably at least 95% homologous to a polypeptide sequence coπesponding to amino acids 1 - 10 of SEQ ID NO. 288, second amino acid sequence being at least 90 % homologous to amino acids 18 - 106 of SEQ ID NO. 349, which also coπesponds to amino acids 11 - 99 of SEQ ID NO. 288, a third (bridging) amino acid sequence comprising D, and a fourth amino acid sequence being at least 90 % homologous to amino acids 179 - 399 of SEQ ID NO. 349, which also conesponds to amino acids 101 - 321 of SEQ ID NO. 288, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 288, comprising a polypeptide being at least 10%), 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 NETEAEQSYV ofSEQ ID NO. 288. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 288, 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 LDY having a structure as follows (numbering according to SEQ ID NO. 288): a sequence starting from any of amino acid numbers 99-x to 99; and ending at any of amino acid numbers 101 + ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 289, 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 sequence coπesponding to amino acids 1 - 15 of SEQ ID NO. 289, and a second amino acid sequence being at least 90 %> homologous to coπesponding to amino acids 203 - 399 of SEQ ID NO. 349, which also coπesponds to amino acids 16 - 212 of SEQ ID NO. 289, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 289, 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% homobgous to the sequence MSSWLSAGSPSSLSV of SEQ ID NO. 289. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 290, 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 sequence coπesponding to amino acids 1 - 13 of SEQ ID NO. 290, and a second amino acid sequence being at least 90 % homologous to amino acids 280 - 399 of SEQ ID NO. 349, which also coπesponds to amino acids 14 - 133 of SEQ ID NO. 290, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided a isolated polypeptide encoding for a head of SEQ ID NO. 290, 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
MCRGYSTLLNPVS of SEQ ID NO. 290. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 291, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 246 of SEQ ID NO. 349, which also conesponds to amino acids 1 - 246 of SEQ ID NO. 291, 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 sequence conesponding to amino acids 247 - 252 of SEQ ID NO. 291, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 291, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90%o and most preferably at least about 95% homologous to the sequence SRNWTQ in SEQ ID NO. 291. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 292, 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 sequence coπesponding to amino acids 1 - 10 of SEQ ID NO. 292, second amino acid sequence being at least 90 % homologous to amino acids 26 - 276 of Q96NF5, which also coπesponds to amino acids 11 - 261 of SEQ ID NO. 292, followed by A, and a third amino acid sequence being at least 90 %> homologous to amino acids 278 - 466 of Q96NF5, which also coπesponds to amino acids 263 - 451 of SEQ ID NO. 292, wherein said first, second, A, and third amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 292, 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 MEISLVKCSE of SEQ ID NO. 292 According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 293, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 276 of Q96NF5, which also coπesponds to amino acids 1 - 276 of SEQ ID NO. 293, followed by A, a second amino acid sequence being at least 90 % homologous to amino acids 278 - 372 of Q96NF5, which also coπesponds to amino acids 278 - 372 of SEQ ID NO. 293, and a third amino acid sequence being at least 90 % homologous to amino acids 401 - 466 of Q96NF5, which also coπesponds to amino acids 373 - 438 of SEQ ID NO. 293, wherein said first, A, second, and third amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 293, 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 EE, having a structure as follows: a sequence starting from any of amino acid numbers 372-x to 372; and ending at any of amino acid numbers 373+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 294, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 276 of Q96NF5, which also conesponds to amino acids 1 - 276 of SEQ ID NO. 294, followed by A, a second amino acid sequence being at least 90 % homologous to amino acids 278 - 401 of Q96NF5, which also coπesponds to amino acids 278 - 401 of SEQ ID NO. 294, 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 sequence coπesponding to amino acids 402 - 407 of SEQ ID NO. 294, wherein said first, A, second and third amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 294, 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 PNRQDS in
SEQ ID NO. 294. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 295, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 276 of Q96NF5, which also conesponds to amino acids 1 - 276 of SEQ ID NO. 295, followed by A, a second amino acid sequence being at least 90 %> homologous to amino acids 278 - 374 of Q96NF5, which also conesponds to amino acids 278 - 374 of SEQ ID NO. 295, 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 sequence coπesponding to amino acids 375 - 390 of SEQ ID NO. 295, wherein said first, A, second and third amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 295, 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 MSHELFSRFSLRLFGR in SEQ ID NO. 295. According to prefeπed embodiments of the present invention, there is provided ai isolated chimeric polypeptide encoding for SEQ ID NO. 296, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 261 of Q96NF5, which also coπesponds to amino acids 1 - 261 of SEQ ID NO. 296, a second amino acid sequence comprising A, and a third amino acid sequence being at least 90 % homologous to amino acids 263 - 451 of Q96NF5, which also coπesponds to amino acids 263 - 451 of SEQ ID NO. 296, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 297, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 132 of Q9NPI5, which also coπesponds to amino acids 1 - 132 of SEQ ID NO. 297, and a second amino acid sequence being at least 70%o, optionally at least 80%>, preferably at least 85%, more preferably at least 90%) and most preferably at least 95% homologous to a polypeptide sequence conesponding to amino acids 133 - 145 of SEQ ID NO. 297, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 297, comprising a polypeptide being at least 70%o, 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 LPGRHEVPRGALP in SEQ ID NO. 297. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 297, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 109 of Q9NZK3, which also coπesponds to amino acids 1 - 109 of SEQ ID NO. 297, 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 sequence coπesponding to amino acids 110 - 145 of SEQ ID NO. 297, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 297, 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 LVDLYSRRYFLTVPYEECKWRRSLPGRHEVPRGALP in SEQ ID NO. 297. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 298, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 107 of Q9NPI5, which also coπesponds to amino acids 1 - 107 of SEQ ID NO. 298, 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 sequence coπesponding to amino acids 108 - 121 of SEQ ID NO. 298, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefened embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 298, 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
NLPGRHEVPRGALP in SEQ ID NO. 298. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 298, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 107 of Q9NZK3, which also conesponds to amino acids 1 - 107 of SEQ ID NO. 298, 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 sequence conesponding to amino acids 108 - 121 of SEQ ID NO. 298, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 298, 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 NLPGRHEVPRGALP in SEQ ID NO. 298. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 299, comprising a first amino acid sequence being at least 90 % homologous to amino acids 51 - 151 of SEQ ID NO. 350, which also coπesponds to amino acids 1 - 101 of SEQ ID NO. 299. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 300, 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 MSSFSTTT coπesponding to amino acids 1 - 8 of SEQ ID NO. 300, and a second amino acid sequence being at least 90 %> homologous to amino acids 42 - 151 of SEQ ID NO. 350, which also coπesponds to amino acids 9 - 118 of SEQ ID NO. 300, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 300, 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 MSSFSTTT of SEQ ID NO. 300. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 301, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 124 of TRIC_HUMAN, which also conesponds to amino acids 1 - 124 of SEQ ID NO. 301, 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 sequence conesponding to amino acids 125- 137 of SEQ ID NO. 301, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 301, 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 VGRMGSSGTFGVG in SEQ ID NO. 301. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 302, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 8 of TRIC HUMAN, which also conesponds to amino acids 1 - 8 of SEQ ID NO. 302, 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 sequence conesponding to amino acids 36 - 209 of TRIC_HUMAN, which also conesponding to amino acids 9 - 182 of SEQ ID NO. 302, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 302, 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 AK, having a structure as follows: a sequence starting from any of amino acid numbers 8-x to 8; and ending at any of amino acid numbers 9+ ((n-2) - x), in which x varies from 0 to n-2. According to prefeπed embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 303, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 36 of TRICJHUMA , which also coπesponds to amino acids 1 - 36 of SEQ ID NO. 303, 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 sequence conesponding to amino acids 37- 86 of SEQ ID NO. 303, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 303, 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 VGRGFLGAEYRRRRDPRPWEWGEEPGLRRGRGLRGGASGAEFCRGSCSDW in SEQ ID NO. 303. According to prefened embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 304, comprising a first amino acid sequence being at least 90 %> homologous to amino acids 1 - 8 of TPJC_HUMAN, which also conesponds to amino acids 1 - 8 of SEQ ID NO. 304, 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 sequence coπesponding to amino acids 9- 13 of SEQ ID NO. 304, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to prefeπed embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 304, 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 VRAAG in SEQ ID NO. 304. According to prefeπed embodiments of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence in any one of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK,
H88495, Z36249, FLJ26352, HSACMHCP. Preferably, the amino acid sequence coπesponds to any insertion, including a bridge, edge portion, tail, or head as described herein. Preferably, the antibody is capable of differentiating between a splice variant having the epitope and a coπesponding known protein. According to prefeπed embodiments of the present invention, there is provided a kit for detecting heart disorders, comprising a kit detecting overexpression of a splice variant. 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 in any one of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK, H88495, Z36249, FLJ26352, HSACMHCP. Optionally, the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence in any one of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK, H88495, Z36249, FLJ26352, HSACMHCP. Optionally, 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 prefeπed embodiments ofthe present invention, there is provided a method for detecting heart disorders, comprising detecting overexpression of a splice variant of any of cluster S67314, N56180, T10377, Z24874, HUMCDDANF, HUMTROPIA, HUMSMCK,
H88495, Z36249, FLJ26352, HSACMHCP. Optionally, detecting overexpression is performed with a NAT-based technology. Also optionally, detecting overexpression is performed with an immunoassay. Preferably, the immunoassay comprises an antibody as described herein. According to prefeπed embodiments of the present invention, there is provided a biomarker capable of detecting heart disorders, comprising any of the above nucleic acid sequences or a fragment thereof, or amino acid sequences or a fragment thereof. According to prefeπed embodiments of the present invention, there is provided a method for screening for heart disorders, comprising detecting cardiac disease cells or tissue with a biomarker or an antibody. According to prefeπed embodiments of the present invention, there is provided a method for diagnosing heart disorders, comprising detecting heart cells or tissue with a biomarker or an antibody. According to preferred embodiments of the present invention, there is provided a method for monitoring disease progression, or treatment efficacy, or relapse of heart disorders, or any combination thereof, comprising detecting heart cells or tissue with a biomarker or an antibody or a method or assay as described herein. According to prefeπed embodiments of the present invention, there is provided a method of selecting a therapy for heart disorders, comprising detecting heart disorder cells with a biomarker or an antibody or a method or assay as described herein and selecting a therapy according to the detection. A heart disorder and/or cardiac disease and/or cardiac pathology optionally comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, assessing the size of infarct in Myocardial infarct. According to prefeπed 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. 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), ohgonucleotides (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 Figure 1 shows a schematic summary of quantitative real-time PCR analysis. Figure 2 is a histogram showing expression of ESTs in each category, as "parts per million". Figures 3 & 4 are histograms showing expression of ohgonucleotides in various tissues, prob 205738_s_at & prob 214285_at. Figure 5A is a histogram showing specific expression of variant FABH_HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues. Figure 5B is a histogram showing specific expression of variant FABH_HUMAN protein transcripts. Figure 6 is a histrogram showing expression of FABH HUMAN known protein transcripts. Figure 7 is a histogram showing expression of the number of heart tissue-specific clones in libraries/sequences. Figure 8 is a histogram showing the actual expression of ohgonucleotides in various tissues, including heart tissue, prob 207317_s_at. Figure 9 is a histogram showing specific expression of the above- indicated Calsequestrin, cardiac muscle isoform transcripts in sequence N56180, heart tissue samples. Figure 10 is a histogram showing specific expression of the above -indicated
Calsequestrin, cardiac muscle isoform transcripts in heart tissue samples as opposed to other tissues. Figure 11 is a histogram showing expression of concerning the number of heart tissue- specific clones in libraries/sequences. Figure 12 is a histogram showing specific expression of Q96NF5 transcripts in sequence
T 10377 in heart tissue samples. Figure 13 is a histogram showing specific expression of the Q96NF5 transcripts in sequence T10377 junc29-33 heart tissue samples. Figure 14 is a histogram showing specific expression of the above- indicated Q96NF5 transcripts T10377 seg2-3 in heart tissue samples. Figure 15 is a histogram concerning the expression of the number of heart-specific clones in libraries/sequences. Figure 16 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 221051_s_at, including heart. Figure 17A is a histogram concerning the expressions of ESTs in number of heart tissue- specific clones in libraries/sequences; Figure 17B is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 209957_s-at, including heart tissue. Figure 18 is a histogram showing expression of known protein transcript for HUMCDDANF_T4. Figure 19 is a histogram concerning expression of ESTs, the number of heart tissue- specific clones in libraries/sequences Figure 20 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 205742_at, including heart tissue. Figure 21A is a histogram showing specific expression of the above- indicated TRIC_HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts in sequence HUMTROPIA seglO in heart tissue. Figure 21 A is a histogram showing specific expression of the TRIC_HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts in sequence HUMTROPIA seg22 in heart tissue. Figure 22 is a histogram showing specific expression ofthe HUMTROPIA known protein sequence in heart tissue. Figure 23 is a histogram showing ESTs concerning the number of heart tissue -specific clones in libraries/sequences Figure 24 is a histogram concerning the actual expression of ohgonucleotides in various tissues, pob 205295_at, including heart tissue. Figure 25 is a histogram showing ESTs concerning the number of heart tissue -specific clones in libraries/sequences Figure 26 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 207066_at, including heart tissue. Figure 27 is a histogram showing ESTs concerning the number of heart- specific clones in libraries/sequences. Figure 28 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 206029_at, including heart tissue. Figure 29 is a histogram concerning expression of ESTs in the number of heart tissue - specific clones in libraries/sequences. Figure 30 is a histogram concerning the expression of ESTs in number of heart tissue- specific clones in libraries/sequences; Figure 31 is a histogram concerning the actual expression of ohgonucleotides in various tissues, prob 204737_s_at, including heart tissue. Figure 32 is a histogram concerning the actual expression of oligonucleotides in various tissues, prob 216265_x_at, including heart tissue. Figure 33 shows a diagram of a troponin I variant, HUMTROPIA_T7, with regard to introducing a mutation to block an additional ORF. Figure 34 shows Troponin PCR product after second amplification reaction: Lane 1: 1Kb MW marker (GibcoBRL Cat# 15615-016) and Lane 2: PCR product. Figure 35 shows Troponin PCR product sequence. Figure 36: plasmid map of His Troponin T7 pRSET A. Figure 37 shows the complete sequence ofthe plasmid shown in Figure 36. Figure 38 shows the protein sequence of Troponin variant HUMTROPIA_PEA_2 T7, with the HIS-tag marked. Figure 39a shows Coomassie staining analysis of SDS-PAGE containing recombinant HisTroponin; lane 1: Molecular weight marker (ProSieve color, Cambrex, Cat #50550); lane 2: HisTroponinT7 pRSETA TO; lane 3: pRSET A T3; lane 4: pRSET empty vector TO (negative control); lane 5: pRSET empty vector T3 (negative control). Figure 39b shows a Western blot analysis of recombinant HisTroponin: lane 1: His positive control protein; lane 2: HisTroρoninT7 pRSETA TO; lane 3: HisTroponinT7 pRSETA T3; lane 4: pRSET empty vector TO (negative control); lane 5: pRSET empty vector T3
(negative control) and lane 6: molecular weight marker (ProSieve color, Cambrex, Cat #50550). DESCRIPTION OF PREFERRED EMBODIMENTS The present invention is of novel markers for cardiac disease that are both sensitive and accurate. 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, and/or are otherwise expressed at a much higher level and/or specifically expressed in heart. The method of the present invention identifies clusters (genes) which are characterized in that the transcripts are differentially expressed in heart muscle tissue compared with other normal tissues, preferably in comparison to skeletal muscle tissue. In acute conditions under which heart muscle tissue experiences hypoxia (with or without necrosis), intracellular proteins that are not normally secreted can leak through the cell membrane to the extracellular space. Therefore, heart muscle tissue differentially expressed proteins, as through analysis of EST expression, are potential acute heart damage markers. Leakage of intracellular content can also occur in chronic damage to the heart muscle, therefore proteins selected according to this method are potential markers for chronic heart conditions. When a protein that is differentially expressed in heart muscle is secreted, it is even more likely to be useful as a chronic heart damage marker, since secretion implies that the protein has a physiological role exterior to the cell, and therefore may be used by the heart muscle to respond to the chronic damage. This rationale is empirically supported by the non- limiting examples of the proteins BNP (brain natriuretic peptide) and ANF (atrial natriuretic factor), which are differentially expressed heart muscle proteins that are secreted and which were shown to be markers for congestive heart failure. In addition, BNP and ANF are not only differentially expressed in heart tissue, they are also overexpressed dramatically (hundreds of times greater expression) when heart failure occurs. Other heart specific secreted proteins might
" present similar overexpression in chronic damage. Optionally and preferably, the markers described herein are overexpressed in heart as opposed to muscle, as described in greater detail below. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can coπelate with a probable diagnosis of cardiac disease and/or cardiac pathology, including but not limited to cardiac damage. The present invention therefore also relates to diagnostic assays for cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, and methods of use of such markers for detection of cardiac disease and/or cardiac pathology, including but not limited to cardiac damage (alone or in combination), optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample. The present invention therefore also relates to diagnostic assays for cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, and methods of use of such markers for detection of cardiac disease and/or cardiac pathology, including but not limited to cardiac damage (alorie or in combination), optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample. 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 ofthe splice variant is typically highly homologous (often 100% identical) to a portion of the conesponding 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 ofthe conesponding 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 Λo 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_Pl (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_Pl): 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 coπesponding 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 coπesponding 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 coπelates 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 coπelates 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage. 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage. According to optional but prefened 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 prefeπed 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 cardiac disease and/or cardiac pathology, including but not limited to cardiac damage, such that a biomarker may optionally comprise any of the above. According to still other prefeπed embodiments, the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence coπesponding 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, conesponding to a splice variant ofthe 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 occuπing 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 %, at 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 occuπing 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 ofthe 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 ofthe 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. Prefeπed 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); "Cunent Protocols in Molecular Biology" Volumes I- III Ausubel, R. M., ed. (1994); Ausubel et al., "Cunent Protocols in Molecular Biology", John Wiley and Sons, Baltimore, Maryland (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 bio markers ofthe present invention. The oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3' to 5' 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 prefeπed 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. Prefeπed modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid forms can 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; foπuacetyl and thioformacetyl backbones; methylene fonnacetyl 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 CEfe 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). United States 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-thio alkyl, 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 0-6 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 prefeπed base substitutions, even more particularly when combined with 2'-0-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, rncludingRetro-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 5'LTR promoter. Cuπently prefened 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-Choi [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most prefeπed 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 aheady 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 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' 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, Cuπent 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 NaCI, 1 %> SDS and 5 x 10^ cpm 32P labeled probe, at 65 °C, with a final wash solution of 0.2 x 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 NaCI, 1 % SDS and 5 x 106 cpm 32P labeled probe, at 65 °C, with a final wash solution of 1 x 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 x 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 μg/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 x 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 μg/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 x SSC, and final wash at 22 °C; (iii) hybridization solution of 6 x 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 μg/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 occuning 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. Natl. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTeclmology 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 prefeπed 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 prefeπed embodiment, the amplification of the differentially expressed nucleic acids is caπied 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 Cuπent 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 α/., 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 ofthe target sequence become the dominant sequences (in teπns of concentration) in the mixture, they are said to be "PCR- amplified." Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes refeπed 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 Al (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 unifoπn 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 5' 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 (Qβ) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for Qβ 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 Qβ 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 cuπently 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 3' 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 ofthe 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 3'-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the theπnostable 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 prefeπed 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 coπelation 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 canied 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 prefeπed 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 ofthe 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-pah 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 conesponding changes in their electrophoretic mobilities. The fragments to be analyzed, usually PCR products, are "clamped" at one end by a long stretch of GC base pahs (30-80) to allow complete denaturation ofthe 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 prefeπed embodiment of the present invention the step of searching for any ofthe 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, Qβ-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 ofthe 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 coπesponding 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 Monow 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 Viπ, 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. Optionally and preferably, nucleic acid sequence homology (identity) is determined 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. 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 occuπing or artificially induced, either randomly or in a targeted fashion. 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-SO, 0=C-NH, CH2-0, 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-0-0-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 Phenylglycme, 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 bothD- and L- amino acids.
Table 1 non-conventional or modified amino acids which can be used with the present invention.
Table 1
Table 1 Cont.
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., Fab' and F(ab)'2 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, CHI, CH2 and CH3, but does not include the heavy chain variable region. The functional fragments of antibodies, such as Fab, F(ab')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) Fab', 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 Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the fragment ofthe antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab')2 is a dimer of two Fab' 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 o 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 ofthe 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(ab')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 Fab' monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab' 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 etal., 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- deteπnining 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, Fab', F(ab') 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 coπesponding 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 conespond 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, Cuπ. 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 refened 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 coπesponding 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 coπesponding 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(l):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 ha\e been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene reaπangement, 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 ofthe 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 isofoπns 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. Prefeπed 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 125 radiolabelled antibody binding protein (e.g., protein A labeled with f ) 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 ofthe 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 ofthe 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 ofthe present invention. Methods of constructing such display libraries are well known in the art. Such methods are described in, for example, Young AC, et al, "The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neofonnans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes" J Mol Biol 1997 Dec 12;274(4):622-34; Giebel LB et al. "Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities" Biochemistry 1995 Nov 28;34(47): 15430-5; Davies EL et al., "Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes" J Immunol Methods 1995 Oct 12;186(l):125-35; Jones C RT al. "Cuπent trends in molecular recognition and bioseparation" J Chromatogr A 1995 Jul 14;707(l):3-22; Deng SJ et al. "Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries" Proc Natl Acad Sci U S A 1995 May 23;92(l l):4992-6; and Deng SJ et al. "Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display" J Bbl Chem 1994 Apr l;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). It should be noted that Table numbering is restarted within each 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 (June 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gbl36.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 Oct 2003); and RefSeq sequences from December 2003. 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); US patent No: 6,625,545; and U.S. Pat. Appl. 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 be 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 mat was designed to find genes and/or their splice variants that are specifically expressed in cardiac tissue, as opposed to other types of tissues and also particularly as opposed to muscle tissue, by using databases of expressed sequences. Various parameters related to the information in the EST libraries, determined according to classification by library annotation, were used to assist in locating genes and/or splice variants thereof that are specifically and/or differentially expressed in heart tissues. The detailed description of the selection method and of these parameters is presented in Example 1 below.
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 specifically expressed in heart tissue is described hereinbelow.
EST analysis ESTs were taken from the following main sources: libraries contained in Genbank version 136 (June 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gbl36.release.notes) and Genbank version 139 (December 2003); and from the LifeSeq library of Incyte Corporation (ESTs only; Wilmington, DE, USA). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section were used. Library annotation - EST libraries were manually classified according to: 1. Tissue origin 2. Biological source - Examples of frequently used biological sources for construction of EST libraries include cancer cell- lines; normal tissues; cancer tissues; foetal 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.
3. 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 (described in the annotation available in Genbank). It will be appreciated that at times the protocol of library construction is not indicated in the information available about that library. The following rules were followed: EST libraries originating from identical biological samples were 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 heart tissue specific genes
For detection of heart tissue specific clusters, heart tissue libraries/sequences were compared to the total number of libraries/sequences in the cluster and in Genebank, and to the relevant numbers for muscle tissue libraries/sequences. Statistical tools were employed to identify clusters that were heart tissue specific, both as compared to all other tissues and also in comparison to muscle 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; 2. The following equation was then used to determine heart tissue -specific expression t I n — t — as compared to expression in all tissue types for a particular cluster: — / in which n TI N-T- M is the total number of ESTs available for a cluster, while N is the total number of ESTs available in all of the libraries considered in the analysis (effectively all ESTs in Genbank, except for those that were rejected as belonging to contaminated libraries). This ratio was preferably set to be at least about 8, although optionally the ratio could be set to be at least about 5. 3. The following equation was then used to determine heart tissue-specific expression ΛS.
expression in skeletal muscle tissue for a particular cluster: in which t represents the number of heart tissue-specific ESTs for the cluster, while T is the number of all heart tissue- specific ESTs in the analysis; m is the number of skeletal muscle tissue -specific ESTs for the cluster, while M is the number of all skeletal muscle tissue-specific ESTs in the analysis. This ratio was preferably set to be at least about 4, although optionally the ratio could be set to be at least about 2. 4. Fisher exact test P- values were computed for weighted clone counts to check that the counts are statistically significant according to the following function: F(t,T,n,N) which is the probability of a cluster actually being overexpressed in heart tissue, as compared to its overall level of expression. The P-value was preferably set to be less than about le-5, although optionally it could be set to be less than about le-3.
The results obtained are explained in greater detail for each marker below.
Actual Marker Examples The following examples relate to specific actual marker examples. It should be noted that Table numbering is restarted within each example related to a particular Cluster, as indicated by the titles below.
EXAMPLES SECTION This Section relates to Examples of sequences according to the present invention, including 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 heart and non- heart tissue samples. 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). A description ofthe samples used in the panel is provided in Table 1 below. Tests were then performed as described in the Examples below.
Table 1: Tissue samples in testing panel
Materials and Experimental Procedures RNA preparation - RNA was obtained from Clontech (Franklin Lakes, NJ USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com), ABS (Wilmington, DE 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, TX 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 DNasel (Ambion) and purified using RNeasy columns (Qiagen). RT PCR - Purified RNA (1 μg) was mixed with 150 ng Random Hexamer primers (Invitrogen) and 500 μM dNTP in a total volume of 15.6 μl. The mixture was incubated for 5 min at 65 °C and then quickly chilled on ice. Thereafter, 5 μl of 5X Superscriptll first strand buffer (Invitrogen), 2.4μl 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 μl (200units) of Superscriptll (Invitrogen) was added and the reaction (final volume of 25μl) was incubated for 50 min at 42 °C and then inactivated at 70 °C for 15min. 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 (5μl), prepared as described above, was used as a template in ReaVTime 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 15sec, 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=efficiencyΛ"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 noπnalized to the geometric mean of the relative quantities of several housekeeping (HSKP) genes. Schematic summary of quantitative real-time PCR analysis is presented in Figure 1. As shown, the x-axis shows the cycle number. The Gr = 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 products 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 normal tissue samples panel were as follows: RPL19 (GenBank Accession No. NM_000981),
RPL19 Forward primer: TGGCAAGAAGAAGGTCTGGTTAG RPL19 Reverse primer: TGATCAGCCCATCTTTGATGAG RPL19 -amplicon:
TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCAATGCCA ACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA TATA box (GenBank Accession No. NM_003194), TATA box Forward primer : CGGTTTGCTGCGGTAATCAT TATA box Reverse primer: TTTCTTGCTGCCAGTCTGGAC
TATA box ~ -amplicon:
CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACTGATTTT CAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAGTCCAGACTG GCAGCAAGAAA Ubiquitin (GenBank Accession No. BC000449) Ubiquitin Forward primer: ATTTGGGTCGCGGTTCTTG Ubiquitin Reverse primer: TGCCTTGACATTCTCGATGGT Ubiquitin -amplicon:
ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAATGCAGAT CTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA
SDHA (GenBank Accession No. NM_004168) SDHA Forward primer: TGGGAACAAGAGGGCATCTG
SDHA Reverse primer: CCACCACTGCATCAAATTCATG SDHA- amplicon : TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT AGTGGATCATGAATTTGATGCAGTGGTGG
DESCRIPTION FOR CLUSTER S67314
Cluster S67314 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
These sequences are variants of the known protein Fatty acid-binding protein, heart (SwissProt accession identifier FABH_HUMAN; known also according to the synonyms H- FABP; Muscle fatty acid-binding protein; M-FABP; Mammary- derived growth inhibitor; MDGI), refened to herein as the previously known protein. Protein Fatty acid-binding protein, heart is known or believed to have the following functιon(s): FABP are thought to play a role in the intracellular transport of long- chain fatty acids and their acyl-CoA esters. The sequence for protein Fatty acid-binding protein, heart is given at the end of the application, as "Fatty acid-binding protein, heart amino acid sequence" (SEQ ID NO:348). Known polymorphisms for this sequence are as shown in Table 4.
Table 4 - Amino acid mutations for Known Protein
Protein Fatty acid-binding protein, heart localization is believed to be Cytoplasmic.
The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: negative control of cell proliferation, which are annotation(s) related to Biological Process; and lipid 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/>.
The heart-selective diagnostic marker prediction engine provided the following results with regard to cluster S67314. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 2 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 histogram in Figure 2, concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figures 3 - 4, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 13.8; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 2.6; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be l.lOE-25.
One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 2.6, which clearly supports specific expression in heart tissue. As noted above, cluster S67314 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Fatty acid- binding protein, heart. A description of each variant protein according to the present invention is now provided. Variant protein S67314_PEA_1_P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T4. An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end ofthe 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 l O i follows:
Comparison report between S67314JPEA_1_P4 and FABH_HUMAN: l.An isolated chimeric polypeptide encoding for S67314JPEA_1_P4, comprising a first amino acid sequence being at least 70%>, optionally at least 80%, preferably at least 85%o, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence
MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL coπesponding to amino acids 1 - 116 of FABH HUMAN, which also coπesponds to amino acids 1 - 116 of S67314_PEA_1_P4, 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL coπesponding to amino acids 117 - 215 of S67314_PEA_1_P4, wherein said firstand second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1_P4, 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
VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRWSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL in S67314_PEA_1_P4. Comparison report between S67314_PEA_1_P4 and AAP35373 : l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P4, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSrVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL conesponding to amino acids 1 - 116 of AAP35373, which also coπesponds to amino acids 1 - 116 of S67314_PEA_1_P4, and a second amino acid sequence being at least 70%, optionally at least 80%o, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGLNNTNLVGLLGSL coπesponding to amino acids 117 - 215 of S67314_PEA_1_P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1_P4, 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 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGTNNTNLVGLLGSL in S67314_PEA_1_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: intracellularly. The protein bcalization is believed to be intracellular 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 S67314_PEA_1_P4 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 S67314_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Amino acid mutations
Variant protein S67314JPEA_1_P4 is encoded by the following transcript(s): S67314JPEA_1_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_1_T4 is shown in bold; this coding portion starts at position 925 and ends at position 1569. 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 S67314JPEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs
Variant protein S67314_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T5. An alignment is given to the known protein (Fatty acid-binding protein, heart) 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 S67314_PEA_1_P5 and FABH ΪUMAN: l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P5, 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 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL coπesponding to amino acids 1 - 116 of FABH_HUMAN, which also coπesponds to amino acids 1 - 116 of S67314_PEA_1JP5, 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 DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV coπesponding to amino acids 117 - 178 of S67314_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1_P5, 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
DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in S67314_PEA_1_P5. Comparison report between S67314_PEA_1_P5 and AAP35373: l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P5, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL coπesponding to amino acids 1 - 116 of AAP35373, which also conesponds to amino acids 1 - 116 of S67314_PEA_1_P5, 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
DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV coπesponding to amino acids 117 - 178 of S67314_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1_P5, 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 DVLTAWPSIYPvRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in S67314 PEA 1 P5. 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 intracellular 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 S67314_PEA_1_P5 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 S67314_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein accordmg to the present invention). Table 7 - Amino acid mutations
Variant protein S67314_PEA_1_P5 is encoded by the following transcript(s): S67314_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_1_T5 is shown in bold; this coding portion starts at position 925 and ends at position 1458. The transcript also has the following SNPs as listed in Tabte 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 S67314_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs
Variant protein S67314_PEA_1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T6. An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end ofthe 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 S67314_PEA_1_P6 and FABHJHUMAN: l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P6, 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 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL coπesponding to amino acids 1 - 116 of FABH_HUMAN, which also coπesponds to amino acids 1 - 116 of S67314_PEA_1_P6, 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 MEKLQLRNVK conesponding to amino acids 117 - 126 of S67314_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1_P6, 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 MEKLQLRNVK in S67314_PEA_1_P6. Comparison report between S67314_PEA_1_P6 and AAP35373: l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL coπesponding to amino acids 1 - 116 of AAP35373, which also coπesponds to amino acids 1 - 116 of S67314_PEA_1_P6, 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 MEKLQLRNVK coπesponding to amino acids 117 - 126 of S67314_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1_P6, 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 MEKLQLRNVK in S67314_PEA_1_P6. The location of the variant protein was detennined 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: mtracellularly. The protein localization is believed to be intracellular 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 S67314_PEA_1_P6 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 S67314_PEA_1_P6 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 amino acid(s) Previously known SNP? sequence 53 K -> R Yes
Variant protein S67314_PEA_1_P6 is encoded by the following xranscript(s): S67314__PEA_1_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_1_T6 is shown in bold; this coding portion starts at position 925 and ends at position 1302. 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 S67314_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs
Variant protein S67314_PEA_1_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T7. An alignment is given to the known protein (Fatty acid -binding protein, heart) at the end ofthe 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 S67314_PEA_1_P7 and FABHJHUMAN: l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSL coπesponding to amino acids 1 - 24 of FABH_HUMAN, which also coπesponds to amino acids 1 - 24 of S67314_PEA_1_P7, 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 AHILITFPLPS conesponding to amino acids 25 - 35 of S67314_PEA_1_P7, and a third amino acid sequence being at least 90 %> homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSI VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA coπesponding to amino acids 25 - 133 of FABH HUMAN, which also coπesponds to amino acids 36 - 144 of S67314_PEA_1_P7, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of S67314_PEA_1_P7, 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 AHILITFPLPS, coπesponding to S67314_PEA_1_P7.
Comparison report between S67314_PEA_1 JP7 and AAP35373: l.An isolated chimeric polypeptide encoding for S67314_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to
MVDAFLGTWKLVDSKNFDDYMKSL coπesponding to amino acids 1 - 24 of AAP35373, which also conesponds to amino acids 1 - 24 of S67314_PEA_1_P7, 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
AHILITFPLPS coπesponding to amino acids 25 - 35 of S67314_PEA_1_P7, and a third amino acid sequence being at least 90 % homologous to
GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSI
VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA coπesponding to amino acids 25 - 133 of AAP35373, which also coπesponds to amino acids 36 - 144 of
S67314_PEA_1_P7, 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 S67314_PEA_1_P7, 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 AHILITFPLPS, coπesponding to S67314_PEA_1_P7. The location of the variant protein was detennined 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 intracellular 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 S67314_PEA_1_P7 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 S67314_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations
Variant protein S67314_PEA_1_P7 is encoded by the following transcript(s): S67314_PEA_1_T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_1_T7 is shown in bold; this coding portion starts at position 925 and ends at position 1356. 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 S67314_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs
As noted abo-ve, cluster S67314 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 S67314_PEA_l_node_0 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): S67314_PEA_1_T4, S67314_PEA_1_T5, S67314_PEA_1_T6 and S67314_ PEA_1_T7. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts
Segment cluster S67314_PEA_l_node_l l 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): S67314_PEA_1_T4. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts
Segment cluster S67314_PEA_l_node_13 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): S67314_PEA_1_T7. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts
Segment cluster S67314_PEA_l_node_15 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): S67314_PEA_1_T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
Segment cluster S67314_PEA_l_node_17 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): S67314_PEA_1_T6. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts
Segment cluster S67314JPEA_l_node_4 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): S67314_PEA_1_T4, S67314_PEA_1_T5, S67314_PEA_1_T6 and S67314_PEA_1_T7. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts
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 S67314_PEA_l_node_10 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): S67314_PEA_1_T4, S67314_PEA_1_T5, S67314_PEA_1_T6 and S67314_PEA_1_T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster S67314_PEA_l_node_3 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): S67314_PEA_1_T7. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: /tmp/EQ0nMn6tqU/R73CUVKUk5 :FABH_HUMAN
Sequence documentation: Alignment of: S67314_PEA_1_P4 x FABH_HUMAN
Alignment segment 1/1:
Quality: 1095.00 Escore: 0 Matching length: 115 Total length: 115 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
2 VDAF GT KLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDI T 51 I I I I 11 I I I I I III I I I I I I I 11 I I I 1 I 1 I I I I II 11111 I I I I I I I I I I 1 VDAFLGTWKLVDSKNFDDYMKS GVGFATRQVASMTKPTTIIEKNGDILT 50
52 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVH QK DGQ 101
51 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 100
102 ETTLVRELIDGKLIL 116 I I I I I I I I I 1 I I I I I 101 ETTLVRELIDGKLIL 115
Sequence name: /tmp/EQ0nMn6tqU/R73CUVKUk5 :AAP35373
Sequence documentation:
Alignment of: S6731 _PEA_1_P4 x AAP35373
Alignment segment 1/1:
Quality: 1107.00 Escore: 0 Matching length: 116 Total length: 116 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0 Alignment :
1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 1 I I I I I I I I I I I I I I 1 I I I I I II I I I I I I I 1 I 1111 I I I I I 1 I I I I 1 I I I 1 MVDAFLGT KLVDSKNFDDYMKS GVGFATRQVASMTKPTTI1EKNGDIL 50
51 T KTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100 I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I ! 1 I 1 I I I I I I 1 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100
101 QETTLVRE IDGKLIL 116 I I I 11 I I I I I I I 1 I I I 101 QETTLVRELIDGKLIL 116
Sequence name: /tmp/ql4YPIBbdQ/SeofJfCmJW: FABH_HUMAN
Sequence documentation:
Alignment of: S6731 _PEA_1_P5 x FABH_HUMAN
Alignment segment 1/1:
Quality: 1095.00 Escore: 0 Matching length: 115 Total length: 115 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment:
2 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 51 I I I I I I I I I I I I I I I I 1 I I II 11 I II I I II I I I I I I I I I I I I I I I II II I 1 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 50 . . . . . 52 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQK DGQ 101 I 11 I I I I I I I I II I I 11 I I I I I I I II I II I I I 1 I II I I I I I I I I I I I I 11 51 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQK DGQ 100 102 ETTLVRELIDGKLIL 116
101 ETTLVRELIDGKLIL 115
Sequence name: /tmp/ql4YPIBbdQ/SeofJfCmJW:AAP35373
Sequence documentation:
Alignment of: S67314_PEA_1_P5 x AAP35373
Alignment segment 1/1:
Quality: 1107.00 Escore: 0 Matching length: 116 Total length: 116 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment:
1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 1 I I II I I I I I I I I I I I I I I I 1 II I 1 I II I I 1 I I I I I I I I I I I II I I 1 I I I 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50
51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100 I I I II 111 I I 111 I I I I I I I I II I I I II I I I I 11 I I I 1 I I I I II I I I I I 1 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100
101 QETTLVRELIDGKLIL 116 I I I I I II I I I 1 I I I I I 101 QETTLVRELIDGKLIL 116
Sequence name: /tmp/PXra2DxLlv/Q8GTrzNMVX:FABH_HUMAN
Sequence documentation : Alignment of : S 67314__PEA_1_P6 x FABH_HUMAN
Alignment segment 1/1:
Quality: 1095.00 Escore 0 Matching length: 115 Total length 115 Matching Percent Similarity: 100.00 Matching Percent Identity 100.00 Total Percent Similarity: 100.00 Total Percent Identity 100.00 Gaps : 0
Alignment :
2 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 51 I I I II 11 I I I I I I I 11 I 11 I I 11 I I 1 I III I I I I I I I I I I I I I I I I I I I 1 1 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 50
52 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 101 I I I I I I 1 I I I I I 1 I 1 I I II I I II I I I 1 I I I 1 I I II I I I I I II I I 1 I I I I I 51 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQK DGQ 100
102 ETTLVRELIDGKLIL 116 1 I I I 1 I I I 11 I 1 I I I 101 ETTLVRELIDGKLIL 115
Sequence name: /tmp/PXra2DxLlv/Q8GTrzNMVX: AAP35373
Sequence documentation:
Alignment of: S67314_PEA 1_P6 x AAP35373
Alignment segment 1/1:
Quality: 1107.00 Escore: 0 Matching length: 116 Total length: 116 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0 Al ignment :
1 MVDAFLGT KLVDSKNFDDYMKSLGVGFATRQVASMTKPTTI IEKNGDIL 50 1 I I I I I I I I I I I I I I I I 1 I I I I I 1 I I I I I I I I I I I I I I I I I I I I I 11 I I I 1 MVDAFLGT KLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50
51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100
51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKS1VTLDGGKLVHLQKWDG 100
101 QETTLVRELIDGKLIL 116 I 11 I I I I I I I II I I I I 101 QETTLVRELIDGKLIL 116
Sequence name: /tmp/xYz yViDom/t Du3T69pd:FABH_HUMAN
Sequence documentation:
Alignment of: S67314_PEA_1_P7 x FABH_HUMAN
Alignment segment 1/1:
Quality: 1160.00 Escore: 0 Matching length: 132 Total length: 143 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 92.31 Total Percent Identity: 92.31 Gaps : 1
Alignment:
2 VDAFLGT KLVDSKNFDDYMKSLAHILITFPLPSGVGFATRQVASMTKPT 51
1 VDAFLGTWKLVDSKNFDDYMKSL GVGFATRQVASMTKPT 39
52 TIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGG 101 1 I I II I I I I I II II I I I I I I I I I I I I I I I 1 I II I I II I I I I I I I I I I I I I 40 TIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGG 89 102 KLVHLQK DGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 144 I 1 I I I I I I I I I I I I I I I I 1 I I 1 I I I I I I I I I I I I I I I I I I I I 1 90 KLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 132
Sequence name: /tmp/xYzWyViDom/twDu3T69pd:AAP35373
Sequence documentation:
Alignment of: S67314_PEA_1_P7 x AAP35373
Alignment segment 1/1:
Quality: 1172.00 Escore: 0 Matching length: 133 Total length: 144 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 92.36 Total Percent Identity: 92.36 Gaps : 1
Alignment :
1 MVDAFLGT KLVDSKNFDDYMKSLAHILITFPLPSGVGFATRQVASMTKP 50 I I I I 1 I I I I I I 1 I I I I I I I I I I I I I I I 1 I I I I I I I I I I I 1 MVDAFLGTWKLVDSKNFDDYMKSL GVGFATRQVASMTKP 39 51 TTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDG 100 I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 40 TTI IEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDG 89
101 GKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 144 I I I I I I I I I I I I I I I I 1 1 I I I I 1 I I I I I I I I I I I I I I I I I I I I I 90 GKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 133
Expression of FABH_HUMAN Fatty acid-binding protein transcripts which are detectable by amplicon as depicted in sequence name S67314 specifically in heart tissue. Expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by or according to segll, S67314 amplicon(s) and S67314 segl lF and S67314 segllR primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin- amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA- amplicon) 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 was then divided by the median of the quantities of the heart samples (Sample Nos. 44, 45, 46, Table 1, "Tissue samples in testing panel", above), to obtain a value of fold up-regulation for each sample relative to median of the heart. Figure 5 A is a histogram showing specific expression of the above -indicated
FABH HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 5A, the expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non heart tissue sample Nos. 1-11,13-21,23-26,28-43, 47-74, 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: S67314 segl lF forward primer; and S67314 segl IR 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: S67314 segl l. S67314 segl lF (SEQ ID NO:61): TCCCCTGAGAGCTGTAGAAGCT S67314 segl IR (SEQ ID NO:62): CGGCCTGTGTGAGTCCAAA S67314 segl 1(SEQ ID NO:63):
TCCCCTGAGAGCTGTAGAAGCTGGGACAAGAGAGTGGTTGTGGGTCAGGGTGGTAT CAGGTGGGAATTTTCTGTGTAGTGGCTTTGGACTCACACAGGCCG Expression ofFABH_HUMAN Fatty acid-binding protein S67314 transcripts, which are detectable by amplicon as depicted in sequence name S67314 seg 15 specifically in heart tissue Expression of FABHJHUMAN Fatty acid-binding protein transcripts detectable by or according to segl5 node(s), S67314 segl5 amplicon(s) and S67314 segl5F and S67314 segl5R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin- amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA- amplicon), was measured similarly. For each RT sample, the expression of the above amplicons was normalized to the geometric mean ofthe quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median ofthe quantities of the heart samples (Sample Nos. 44-46, Table 1, above "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median ofthe heart. Figure 5B is a histogram showing specific expression of the above -indicated FABH_HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 5B, the expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non-heart tissue sample Nos. 1-9, 11-21, 23-26, 28-43, 47-74 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: S67314 segl5F forward primer; and S67314 segl5R 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: S67314 segl5. S67314 segl5F (SEQ ID NO:64) Forward primer: TTCCTTGGCATCTCCAATGG S67314 segl5R (SEQ ID NO:274) Reverse primer: GCCAACTCTCAGCTCCTCCC S67314 segl5 (SEQ ID NO:275) Amplicon: TTCCTTGGCATCTCCAATGGAGTAGAGAGAAGGCAACAAAGCTTCTCAGACCCACA TTACCGAGCTATAACAACCATGGCTGGGAGGAGCTGAGAGTTGGC Expression of FABH_HUMAN Fatty acid-binding protein S67314 transcripts which are detectable by amplicon as depicted in sequence name S67314seg4 specifically in heart tissue Expression of FABHJHUMAN Fatty acid-binding protein transcripts detectable by or according to seg4 node(s), S67314 seg4 amplicon(s) and primers S67314seg4F and S67314seg4R was measured by real time PCR (this transcript coπesponds to the known or WT protein). In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin- amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), 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 was then divided by the median of the quantities of the heart samples (Sample Nos. 44-46, Table 1, above), to obtain a value of relative expression for each sample relative to median of the heart samples. Figure 6 is a histogram showing relative expression of the above-indicated FABH_HUMAN Fatty acid-binding protein transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 6, the expression of FABH_HUMAN Fatty acid-binding protein transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in the other samples (Sample Nos. 44-46 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: S67314seg4F forward primer; and S67314seg4R 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: S67314seg4.
Forward primer S67314seg4F (SEQ ID NO:276): CCAAGCCTACCACAATCATCG Reverse primer S67314seg4R (SEQ ID NO:277): CTCCACCCCCAACTTAAAGCT Amplicon S67314seg4 (SEQ ID NO:278): CCAAGCCTACCACAATCATCGAAAAGAATGGGGACATTCTCACCCTAAAAACACAC AGCACCTTCAAGAACACAGAGATCAGCTTTAAGTTGGGGGTGGAG
DESCRIPTION FOR CLUSTER N56180
Cluster N56180 features 7 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
These sequences are variants of the known protein Calsequestrin, cardiac muscle isoform precursor (SwissProt accession identifier CAQ2_HUMAN; known also according to the synonyms Calsequestrin 2), refeπed to herein as the previously known protein. Protein Calsequestrin, cardiac muscle isoform precursor is known or believed to have the following function(s): Calsequestrin is a high- capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. The release of calcium bound to calsequestrin through a calcium release channel triggers muscle contraction. The protein binds 40 to 50 moles of calcium. The sequence for protein Calsequestrin, cardiac muscle isoform precursor is given at the end of the application, as "Calsequestrin, cardiac muscle isoform precursor amino acid sequence" (SEQ ID NO:349). Known polymoφhisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein
Protein Calsequestrin, cardiac muscle isoform precursor localization is believed to be in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: striated muscle contraction; heart development; muscle development, which are annotation(s) related to Biological Process; calcium storage, which are annotation(s) related to Molecular Function; and smooth endoplasmic reticulum, 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/proj ects/LocusLink/>.
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster N56180. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 7 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 histogram in Figure 7, concerning the number of heart-specific clones in libraries/sequences; as well as with regard to the histogram in Figure 8, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs was found to be 11; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs was found to be 2.4; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 4.70E-14. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non- heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs was found to be 2.4, which clearly supports specific expression in heart tissue.
As noted above, cluster N56180 features 7 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Calsequestrin, cardiac muscle isoform precursor. A description of each variant protein according to the present invention is now provided. Variant protein N56180_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T1. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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 N56180_P2 and CAQ2_HUMAN: l.An isolated chimeric polypeptide encoding for N56180_P2, comprising a first amino acid sequence being at least 90 % homologous to MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEP VSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYIL KGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAFERIEDYIKLIGFFKSEDSEYY KAFEEAAEHFQPYIKFFATFDKGV conesponding to amino acids 1 - 203 of CAQ2 HUMAN, which also coπesponds to amino acids 1 - 203 of N56180_P2, 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 LWLTPVIPTLWEADGGGLHEPWSWRPAWATWLQRNYL coπesponding to amino acids 204 - 240 of N56180_P2, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of N56180_P2, 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 LWLTPVIPTLWEADGGGLHEPWSWRPAWATWLQRNYL in N56180JP2.
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 or localized in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein. 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 N56180_P2 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 N56180_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention).
Table 7 - Amino acid mutations
Variant protein N56180JP2 is encoded by the following transcript(s): N56180_T1, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript N56180_T1 is shown in bold; this coding portion starts at position 242 and ends at position 961. 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 N56180_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs
Variant protein N56180_P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T3. An alignment is given to the lαiown protein (Calsequestrin, cardiac muscle isoform 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 N56180_P4 and CAQ2_HUMAN: l.An isolated chimeric polypeptide encoding for N56180_P4, comprising a first amino acid sequence being at least 90 % homologous to MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEP VSSDKVTQKQFQLKEIVLE coπesponding to amino acids 1 - 78 of CAQ2JTUMAN, which also coπesponds to amino acids 1 - 78 of N56180_P4, 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 HWQISQWWLHFQTPREEGKMKLLELSESADGAAWKRWGGNSNTHRIQ coπesponding to amino acids 79 - 125 of N56180_P4, and a third amino acid sequence being at least 90 % homologous to LVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVE FLLDLIEDPVEIISSKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATF DKGVAKXLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMF ETWEDDLNGΓHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWΓDPDDFPLLVAY WEKTFKIDLFRPQIGVNNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKTNTEDDD EDDDDDDNSDEEDNDDSDDDDDE corresponding to amino acids 79 - 399 of CAQ2_HUMAN, which also coπesponds to amino acids 126 - 446 of N56180_P4, 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 N56180_P4, 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 HWQISQWWLHFQTPREEGKMKLLELSESADGAAWKRWGGNSNTHRIQ, coπesponding to N56180_P4.
The location of the variant protein was detennined 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 or localized in the sarcoplasmic reticulum's terminal cistemae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protem has a signal peptide, and neither trans -membrane region prediction program predicts that this protein has a trans- membrane region.. Variant protein N56180_P4 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 N56180_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations
Variant protein N56180_P4 is encoded by the following transcript(s): N56180_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript N56180_T3 is shown in bold; this coding portion starts at position 242 and ends at position 1579. 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 N56180_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs
Variant protein N56180_P5 according to the present invention has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) N56180 T4. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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 N56180_P5 and CAQ2 HUMAN: l.An isolated chimeric polypeptide encoding for N56180_P5, comprising a first amino acid sequence being at least 90 % homologous to
MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEP VSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYIL KGDRTIEFDGEFAADVLVEFLLD coπesponding to amino acids 1 - 140 of CAQ2JHUMAN, which also coπesponds to amino acids 1 - 140 of N 6180_P5, and a second amino acid sequence being at least 90 % homologous to
VAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFETW EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKT FKIDLFRPQIGWNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKTNTEDDDEDDD DDDNSDEEDNDDSDDDDDE coπesponding to amino acids 203 - 399 of CAQ2_HUMAN, which also coπesponds to amino acids 141 - 337 of N56180_P5, 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 N56180_P5, 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 DV, having a structure as follows: a sequence starting from any of amino acid numbers 140-x to 140; and ending at any of amino acid numbers 141+ ((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 or localized in the sarcoplasmic reticulum's terminal cistemae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein. 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 N56180_P5 also has the following non- silent SNPs (Single Nucleotide Polymoφhisms) 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 N56180_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations
Variant protein N56180 P5 B encoded by the following transcript(s): N56180_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript N56180_T4 is shown in bold; this coding portion starts at position 242 and ends at position 1252. 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 N56180_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs
Variant protein N56180_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180_T5. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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 N56180_P6 and CAQ2_HUMAN: l.An isolated chimeric polypeptide encoding for N56180_P6, 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 NETEAEQSYV coπesponding to amino acids 1 - 10 of N56180_P6, second amino acid sequence being at least 90 % homologous to RAEEGLNFPTYDGKDRWSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEI VLELVAQVLEFIKAJGFVMVDAKKEAKLAKKL coπesponding to amino acids 18 - 106 of CAQ2_HUMAN, which also coπesponds to amino acids 11 - 99 of N56180JP6, a third (bridging) amino acid sequence comprising D, and a fourth amino acid sequence being at least 90 % homologous to YKAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEEL VEFVKEHQRPTLRRLRPEEMFETWEDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNT DNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLPTA EELEDWIEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE coπesponding to amino acids 179 - 399 of CAQ2 HUMAN, which also coπesponds to amino acids 101 - 321 of N56180_P6, 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 N56180_P6, 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 NETEAEQSYV of N56180_P6. 3.An isolated polypeptide encoding for an edge portion of N56180_P6, 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 LDY having a structure as follows (numbering according to N56180_P6): a sequence starting from any of amino acid numbers 99-x to 99; and ending at any of amino acid numbers 101 + ((n-2) - x), in which x varies from 0 to n-2. Variant protein N56180_P6 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 N56180_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 -Amino acid mutations
Variant protein N56180_P6 is encoded by the following transcript(s): N56180_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript N56180_T5 is shown in bold; this coding portion starts at position 1 and ends at position 964. 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 N56180_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs
Variant protein N56180_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T6. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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 N56180_P7 and CAQ2JHUMAN: l.An isolated chimeric polypeptide encoding for N56180_P7, 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 MSSWLSAGSPSSLSV coπesponding to amino acids 1 - 15 of N56180_P7, and a second amino acid sequence being at least 90 % homologous to
VAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFETW
EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKT
FKIDLFRPQIGVVNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKΓNTEDDDEDDD
DDDNSDEEDNDDSDDDDDE coπesponding to amino acids 203 - 399 of CAQ2_HUMAN, which also coπesponds to amino acids 16 - 212 of N56180_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a head of N56180_P7, comprising a polypeptide being at least 10%, 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 MSSWLSAGSPSSLSV of N56180_P7.
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 intracellular 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 N56180_P7 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 N56180_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 15 - Amino acid mutations
Variant protein N56180_P7 is encoded by the following transcript(s): N56180_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript N56180_T6 is shown in bold; this coding portion starts at position 71 and ends at position 706. 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 N56180_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 16 - Nucleic acid SNPs
Variant protein N56180_P8 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180_T7. An alignment is given to the known protein (Calsequestrin, cardiac muscle isofonn 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 N56180JP8 and CAQ2JHUMAN: l.An isolated chimeric polypeptide encoding for N56180_P8, 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 MCRGYSTLLNPVS conesponding to amino acids 1 - 13 of N56180_P8, and a second amino acid sequence being at least 90 %> homologous to DGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTD ADSVWMEIPDDDDLPTAEELEDWIEDVLSGKLNTEDDDEDDDDDDNSDEEDNDDSDD DDDE coπesponding to amino acids 280 - 399 of CAQ2JHUMAN, which also coπesponds to amino acids 14 - 133 of N56180_P8, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of N56180_P8, 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 MCRGYSTLLNPVS of N56180_P8.
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 fillows 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 N56180_P8 is encoded by the following transcript(s): N56180_T7, for which the sequence(s) is/are given at the end ofthe application. The coding portion of transcript N56180 T7 is shown in bold; this coding portion starts at position 97 and ends at position 495. 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 N56180_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 17 - Nucleic acid SNPs
Variant protein N56180_P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) N56180 T8. An alignment is given to the known protein (Calsequestrin, cardiac muscle isoform 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 N56180_P9 and CAQ2_HUMAN: l.An isolated chimeric polypeptide encoding for N56180JP9, comprising a first amino acid sequence being at least 90 %> homologous to MKRTHLFrVGIYFLSSCRAEEGLNFPTYDGKDRVNSLSEKNFKQVLKKYDLLCLYYHEP NSSDKVTQKQFQLKEINLELVAQVLEHK GFVMVDAKKEAKLAKKLGFDEEGSLYIL KGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAFERIEDYIKLIGFFKSEDSEYY KAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVE FVKEHQR coπesponding to amino acids 1 - 246 of CAQ2_HUMAN, which also coπesponds to amino acids 1 - 246 of N56180_P9, 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 SRNWTQ coπesponding to amino acids 247 - 252 of N56180_P9, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a tail of N56180_P9, 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 SRNWTQ in N56180_P9.
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 or localized in the sarcoplasmic reticulum's terminal cistemae luminal spaces of cardiac and slow skeletal muscle cells like the WT protein. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protem has a signal peptide, and neither trans -membrane region prediction program predicts that this protein has a trans- membrane region.. Variant protein N56180_P9 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 N56180JP9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 18 -Amino acid mutations
Variant protein N56180_P9 is encoded by the following transcript(s): N56180_T8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript N56180_T8 is shown in bold; this coding portion starts at position 242 and ends at position 997. 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 lαiown or not; the presence of known SNPs in variant protein N56180_P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 19 - Nucleic acid SNPs
As noted above, cluster N56180 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 N56180_node_2 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): N56180_T1, N56180_T3, N56180 T4 and N56180JT8. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster N56180_node_20 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): N56180 T1, N56180JT3, N56180 T4, N56180 T5, N56180_T6 and N56180_T8. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
Segment cluster N56180_node_22 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): N56180 T8. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
Segment cluster N56180_node_28 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): N56180 T7. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position [ Segment ending position N56180 T7 1 136
Segment cluster N56180_node_34 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): N56180_T1, N56180 T3, N56180 T4, N56180_T5, N56180 T6 and N56180_T7. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts
Segment cluster N56180_node_36 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): N56180 T1, N56180JT3, N56180 T4, N56180 T5, N56180 T6 and N56180_T7. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts
Segment cluster N56180_node_4 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): N56180_T1, N56180 T3, N56180 T4, N56180 T5 and N56180_T8. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts
Segment cluster N56180_node_6 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): N56180 T3. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts
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 N56180_node_0 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): N56180 T5. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts
Segment cluster N56180_node_ 10 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): N56180 T1, N56180JT3, N56180 T4 and N56180_T8. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts
Segment cluster N56180_node__12 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): N56180_T1, N56180JT3 and N56180_T8. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts
Segment cluster N56180_node_14 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): N56180_T1, N56180_T3, N56180_T5 and N56180_T8. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts
Segment cluster N56180_node_16 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): N56180_T1. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts
Segment cluster N56180_node_18 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): N56180_T6. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts
Segment cluster N56180_node_24 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): N56180_T1, N56180 T3, N56180 T4, N56180 T5 and N56180_T6. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts
Segment cluster N56180_node_26 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): N56180_T1, N56180 T3, N56180 T4, N56180_T5 and N56180 T6. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts
Segment cluster N56180_node_29 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): N56180_T1, N56180JT3, N56180JT4, N56180 T5, N56180 T6 and N56180 I7. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts
Segment cluster N56180_node_3 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): N56180_T1, N56180 T3, N56180JT4 and N56180_T8. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts
Segment cluster N56180_node_31 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): N56180_T1, N56180_T3, N56180_T4, N56180_T5, N56180_T6 and N56180_T7. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts
Segment cluster N56180_node_33 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): N56180_T1, N56180 T3, N56180 T4, N56180JT5, N56180_T6 and N56180_T7. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts
Segment cluster N56180_node_35 according to the present invention can be found in the following transcript(s): N56180 T1, N56180 T3, N56180 T4, N56180JT5, N56180 T6 and N56180_T7. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts
Segment cluster N56180_node_8 according to the present invention is supported by 25 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): N56180_T1, N56180_T3, N56180 T4, N56180_T5 and N56180_T8. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: /tmp/QH4bp760jk/sAp7DyaTKD:CAQ2_HUMAN Sequence documentation:
Alignment of: N56180 P2 x CAQ2_HOMAN
Alignment segment 1/1:
Quality: 1955.00 Escore: 0 Matching length: 203 Total length: 203 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50
1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50
51 LLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEA 100 I I I I I I I I I I I I 1 I I 11 I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I 1 I II I 51 LLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEA 100
101 KLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIIS 150 I I I I I II I I I I I I I I II I I I I I I I I I I I I I I I 1 I I 1 I I 1 I I I 1 I I I 1 I I I 101 KLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIIS 150
151 SKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFD 200 I I I I I I I I I I I I I I I I I II I I I I 1 I I I I I I I I I I I I 1 I I I 11 I I I I I I I I 151 SKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFD 200
201 KGV 203
201 KGV 203
Sequence name: /tmp/VtcMdCiEuz/FlmsgLbcq4 : CAQ2_HUMAN
Sequence documentation:
Alignment of: N56180_P4 x CAQ2_HUMAN
Alignment segment 1/1:
Quality: 3806.00 Escore: 0 Matching length: 399 Total length: 446 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 89.46 Total Percent Identity: 89.46 Gaps : 1 Alignment :
1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50 I I I 1 I I I I I 1 I I I I I 11 I I I I I I I 1 I I I I I I I I I I 11 I 1 I I I I I 1 I I I I I 1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50
51 LLCLYYHEPVSSDKVTQKQFQLKEIVLEHWQISQWWLHFQTPREEGKMKL 100 I I I 1 I I I I I I I 1 I I I II I I I I I I I 1 I I I 51 LLCLYYHEPVSSDKVTQKQFQLKEIVLE 78
101 LELSESADGAAWKRWGGNSNTHRIQLVAQVLEHKAIGFVMVDAKKEAKLA 150 I I I I I I I I 1 I I I I I 1 I I I I I I 1 I I I 79 LVAQVLEHKAIGFVMVDAKKEAKLA 103 . . . . . 151 KKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKL 200 11 I I I I I I I I I I I I II I 1 I I I 11 I I I I I I I I I I I I I I I I I I I I I I I I I I I 104 KKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKL 153 201 EVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFDKGV 250 I I I I I I I I I I 1 I I I I I I I 1 I II I I 1 I I 1 I 1 I I I I I 1 I I I I 1 I I I I I I I I I 154 EVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFDKGV 203 251 AKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLR 300 I I I 1 I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I 1 I I 11 I I I I I I 1 I I I I I 204 AKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLR 253
301 PEEMFETWEDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSI 350 1 I I I I 1 I I I I I 11 I I I I 1 I 1 I II I I I I I I I I I I I I I I I I I I I I I I II I I I 254 PEEMFET EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSI 303 351 LWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLP 400 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 11 I I I I 1 I I I I I 1 I I I I I 304 LWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLP 353
401 TAEELEDWIEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 446 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I 354 TAEELED IEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 399 Sequence name: /tmp/lRixkfCRfD/JDL7BwYPJs : CAQ2_HUMAN
Sequence documentation:
Alignment of: N56180_P5 x CAQ2_HUMAN
Alignment segment 1/1: Quality: 3202.00 Escore: 0 Matching length: 337 Total length: 399 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 84.46 Total Percent Identity: 84.46 Gaps : 1
Alignment :
1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50 I I I I I I I I I I I I I I I I I I I I I II I I 1 I I I I I I I I I I I I I I I I I I I I 1 I I I 1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50
51 LLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEA 100 I I I I I I I I I I I I 1 I I I I I I II II 1 I I I I I 1 I I I I I I 1 I 1 I I 1 I I I I I II I 51 LLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEA 100 . . . . . 101 KLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLD 140 I I I I I 1 I I I I I I 1 I I I I 1 I 1 I II I II I I I I I I I 1 I I I 1 I I 101 KLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIIS 150 140 140
151 SKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFD 200 141 ..VAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLR 188 I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I 201 KGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLR 250
189 RLRPEEMFET EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPD 238 1 I I I I I I I I I I I I I I 1 I I I I I I 1 I I I 1 1 I I I I I I 1 I I I I I I I I I I I 1 I I I 251 RLRPEEMFET EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPD 300
239 LSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSV MEIPDDD 288 I II I I I 1 I I I I I I I I I I I I I I II I I I I I 11 I I I I I I I I I I 1) I I I 1 I I I I 301 LSILWIDPDDFPLLVAY EKTFKIDLFRPQIGVVNVTDADSV MEIPDDD 350
289 DLPTAEELEDWIEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 337 I I I 1 I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I 11 351 DLPTAEELED IEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 399
Sequence name: /tmp/rs5xPc26iA/XlzfpEDJF7 : CAQ2_HUMAN
Sequence documentation:
Alignment of: N56180_P6 x CAQ2_HUMAN
Alignment segment 1/1: Quality: 2955.00 Escore: 0 Matching length: 314 Total length: 385 Matching Percent Similarity: 99.04 Matching Percent Identity: 99.04 Total Percent Similarity: 80.78 Total Percent Identity: 80.78 Gaps : 1
Alignment :
8 SYVRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDK 57 I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I 1 I I I I I I I I I 1 I I I 15 SSCRAEEGLNFPTYDGKDRWSLSEKNFKQVLKKYDLLCLYYHEPVSSDK 64 58 VTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEAKLAKKLD 100 I II I I I I I I I I I I ) I I I I I I I I I I I I I I II I I I I I I I 1 I I I I 65 VTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSL 114
100 100
115 YILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAFERIEDY 164 101 YKAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEV 136 I I I I I I I 1 I I I I I I I I I I I I I I I 1 I I I I I 1 I I I 1 I I 165 IKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEV 214 . . . . . 137 DFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFET EDD 186 111 I I I I I I I I I I I I I I I I I I 1 I I I I I I 1 I I I I I I I 1 I I I .1 I 111 I I I I I 215 DFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFETWEDD 264 187 LNG1HIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSIL IDPDDFPLL 236 I I I II I I I I I I I I I I II I I I I I I I 1 I I I I I I I I I I I I I I I I 1 I I I I I I I I 265 LNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLL 314 237 VAY EKTFKIDLFRPQIGVVNVTDADSV MEIPDDDDLPTAEELEDWIED 286 I I I I I I I I 11 I I II I I I I 1 I I I I I I I I I I 1 I I I I I I I I I I I 1 I 1 I I I II I 315 VAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLPTAEELEDWIED 364 287 VLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 321 I I I I I I I I 1 I I I I I I I I 1 I I I I I I I I I I I I I 1 I I I 365 VLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 399
Sequence name: /tmp/YOj 6jtvAt2/UVZXGVRVOx:CAQ2_HUMAN
Sequence documentation:
Alignment of: N56180_P7 x CAQ2_HUMAN
Alignment segment 1/1: Quality: 1959.00 Escore: 0 Matching length: 197 Total length: 197 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
16 VAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRL 65 I 1 I I I I I I I I I I I I I I 1 I I I I I I I 1 I I I I I I 1 I 1 1 I I I 1 I I I I I I I I I I I 203 VAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRL 252
66 RPEEMFET EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLS 115 I I I I I I I I I I II 1 I I I I I I 11 II I I 11 I I I I I I I I I I I I I I I I I I I I 11 I 253 RPEEMFET EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLS 302
116 IL IDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDL 165 I I I I I I I I II II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 303 ILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDL 352
166 PTAEELEDWIEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 212 1 I I I I I I I I I I I I I I I I I I I I II 1 I I I I I I 1 I I I I I I I 1 I I I I I I I I 353 PTAEELED IEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE 399
Sequence name: /tmp/kmYMCJlGuB/no5BP02sjR: CAQ2_HUMAN
Sequence documentation:
Alignment of: N56180_P8 x CAQ2_HUMAN
Alignment segment 1/1:
Quality: 1187.00 Escore: 0 Matching length: 120 Total length: 120 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment:
14 DGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRP 63 I I I I 1 I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I II I I 1 I I I I I I I II II I 280 DGYEFLEILKQVARDNTDNPDLSIL IDPDDFPLLVAY EKTFKIDLFRP 329 64 QIGWNVTDADSV MEIPDDDDLPTAEELED IEDVLSGKINTEDDDEDD 113
330 QIGWNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKINTEDDDEDD 379 114 DDDDNSDEEDNDDSDDDDDE 133 1 I I I I I I I I I I I 1 I I I I I I 1 380 DDDDNSDEEDNDDSDDDDDE 399
Sequence name: /tmp/JIYFiyiYEk/c42Jok7Lfq: CAQ2__HUMAN
Sequence documentation:
Alignment of: N56180_P9 x CAQ2_HUMAN
Alignment segment 1/1:
Quality: 2388.00 Escore: 0 Matching length: 246 Total length: 246 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment:
1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50 I I I I I 1 I I I I I I I I I II I I I I I I I 11 I I 1 I I I I I I I I I I I I I I 11 I I 1 I 1 1 MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYD 50 51 LLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEA 100 I I I I I I I I I I II I I I I I I 1 II I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I 51 LLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVLEHKAIGFVMVDAKKEA 100 101 KLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIIS 150 I 11 I I I I I I I I I I I I I I I I I I II I I I I I I I I 1 I I I I I I I I I I I I I I I I I 1 101 KLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIIS 150
151 SKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFD 200 I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I 151 SKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFD 200
201 KGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQR 246 I 1 1 I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I 1 I I 1 1 I I I 1 I I I I 201 KGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQR 246
Expression of Calsequestrin, cardiac muscle isofoπn transcripts which are detectable by amplicon as depicted in sequence name N56180 specifically in heart tissue
Expression of Calsequestrin, cardiac muscle isofoπn transcripts detectable by or according to seg6, N56180 amplicon(s) and N56180 seg6F and N56180 seg6R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM 000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA- amplicon) 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 was then divided by the median of the quantities of the heart samples (Sample Nos. 44, 45, 46, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold upregulation for each sample relative to median of the heart. Figure 9 is a histogram showing specific expression of the above-indicated Calsequestrin, cardiac muscle isoform transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 9, the expression of Calsequestrin, cardiac muscle isoform transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non-heart tissue sample Nos. 1-21,23-26,28,30-43 47-74 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: N56180 seg6F forward primer; and N56180 segδR 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: N56180 seg6. N56180 seg6F (SEQ ID NO:279): ATATCCCAGTGGTGGTTGCATT N56180 seg6R (SEQ ID NO:280): CCCTCCCCAGCGTTTCC N56180 seg6 (SEQ ID NO:335):
ATATCCCAGTGGTGGTTGCATTTCCAAACCCCAAGAGAGGAAGGCAAAATGAAGTT GCTGGAGTTGAGTGAATCTGCAGATGGAGCTGCGTGGAAACGCTGGGGAGGG
Expression of Calsequestrin, cardiac muscle isoform transcripts detectable by or according to seg node(s), N56180 amplicon(s) and N56180 seg F and N56180 seg R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin- amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA- amplicon), was measured similarly. For each RT sample, the expression ofthe above amplicons 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 heart samples (Sample Nos. 44, 45, 46, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the heart. Figure 10 is a histogram showing specific expression of the above -indicated Calsequestrin, cardiac muscle isoform transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 10, the expression of Calsequestrin, cardiac muscle isoform transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most ofthe other samples (non- heart tissue sample Nos. 1-21, 23-26, 28-43, 47-74 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: N56180 seg F forward primer; and N56180 seg R 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: N56180 seg . N56180 seg F (SEQ ID NO:336): TTGATACCACTTAGTGTAGCTCCAGC N56180 seg R (SEQ ID NO:337): TCAAGTAGTTGCTACAGACGCCA N56180 seg (SEQ ID NO:361): TTGATACCACTTAGTGTAGCTCCAGCATGGATCAGCAAACTTTTTCTGTAAAGAACA AAATGGTAAATATTTCAGGTTCTGTGGGCCAGATGGCGTCTGTAGCAACTACTTGA
DESCRIPTION FOR CLUSTER T10377 Cluster T10377 features 6 transcript(s) and 18 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
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster T10377. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 11 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 histogram in
Figure 11, concerning the number of heart- specific clones in libraries/sequences. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 10.9. The expression level of this gene in muscle was negligible; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 8.60E-15. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the expression level of this gene in muscle was negligible, which clearly supports specific expression in heart tissue. As noted above, cluster T10377 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 T10377_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10377_T1 and T10377_T2. 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 protem according to the present invention to each such aligned protein is as follows:
Comparison report between T10377_P2 and Q96NF5 (SEQ ID NO:362): 1. An isolated chimeric polypeptide encoding for T10377_P2, 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 MEISLVKCSE coπesponding to amino acids 1 - 10 of T10377_P2, second amino acid sequence being at least 90 % homologous to ANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGVVR RSDQNQQKEMVVYGWSTSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMR QKIRQLTQELSVSHAQQEYLENHIQTQSSALDRFNAMNSALASDSIGLQKTL VDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVES SQEANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFLK coπesponding to amino acids 26 - 276 of Q96NF5, which also coπesponds to amino acids 11 - 261 of T10377_P2, followed by A, and a third amino acid sequence being at least 90 % homologous to IEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHETEMSG ELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKK LQQKQLLILQLLEKISFLEGENNELQSRLDYLTETQAKTEVETREIGVGCDLL PSQTGRTREIVMPSRNYTPYTRVLELTMKKTLT coπesponding to amino acids 278 - 466 of Q96NF5, which also coπesponds to amino acids 263 - 451 of T10377_P2, wherein said first, second, A, and third amino acid sequences are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a head of T10377_P2, 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 MEISLVKCSE of T10377_P2. 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 intracellular 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 T10377_P2 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 T10377_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Amino acid mutations
Variant protein T10377_P2 is encoded by the following transcript(s): T10377_T1 and S T10377_T2, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10377_T1 is shown in bold; this coding portion starts at position 166 and ends at position 1518. 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 T10377_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs
The coding portion of transcript T10377_T2 is shown in bold; this coding portion starts at position 270 and ends at position 1622. 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 lαiown or not; the presence of known SNPs in variant protein T10377_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs
Variant protein T10377_P5 according to the present invention has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) T10377 T5. 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 T10377_P5 and Q96NF5: 1. An isolated chimeric polypeptide encoding for T10377_P5, comprising a first amino acid sequence being at least 90 % homologous to MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKE QLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGWSTSQLKEEMN YIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQ SSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDK LREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYEEKLQE EQRKHSAEKEALLEETNSFLK coπesponding to amino acids 1 - 276 of Q96NF5, which also coπesponds to amino acids 1 - 276 of T10377_P5, followed by A, a second amino acid sequence being at least 90 % homologous to IEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHETEMSG ELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVE coπesponding to amino acids 278 - 372 of Q96NF5, -w ich also coπesponds to amino acids 278 - 372 of T10377_P5, and a third amino acid sequence being at least 90 % homologous to ENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREΓVMPSRNYTPY TRVLELTMKKTLT coπesponding to amino acids 401 - 466 of Q96NF5, which also ωπesponds to amino acids 373 - 438 of T10377_P5, wherein said first, A, second, and third amino acid sequences are contiguous and in a sequential order. 2. An isolated chimeric polypeptide encoding for an edge portion of T10377_P5, 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 EE, having a structure as follows: a sequence starting from any of amino acid numbers 372-x to 372; and ending at any of amino acid numbers 373+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was detennined 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 one of the two signal- peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.. Variant protein T10377_P5 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 T10377_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations
Variant protein T10377_P5 is encoded by the following transcript(s): T10377 T5, for which the sequence(s) is/are given at the end ofthe application. The coding portion of transcript T10377_T5 is shown in bold; this coding portion starts at position 140 and ends at position 1453. 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 T10377_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs
Variant protein T10377_P6 according to the present invention has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) T10377_T6. 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 T10377_P6 and Q96NF5: 1. An isolated chimeric polypeptide encoding for T10377JP6, comprising a first amino acid sequence being at least 90 % homologous to MLRSTSTVTLLSGGAARTPGAPSKRANVCRLRLTVPPESPVPEQCEKKIERKE QLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGWSTSQLKEEMN YIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQ SSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDK LREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYEEKLQE EQRKHSAEKEALLEETNSFLK conesponding to amino acids 1 - 276 of Q96NF5, which also conesponds to amino acids 1 - 276 of T10377_P6, followed by A, a second amino acid sequence being at least 90 % homologous to IEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHETEMSG ELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKK LQQKQLLILQLLEKISFLEGE corresponding to amino acids 278 - 401 of Q96NF5, which also coπesponds to amino acids 278 - 401 of T10377 P6, 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 PNRQDS coπesponding to amino acids 402 - 407 of T10377_P6, wherein said first, A, second and third amino acid sequences are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a tail of T10377_P6, 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 PNRQDS in T10377_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 one of the two signal- peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.. Variant protein T10377_P6 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 T10377_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Amino acid mutations
Variant protein T10377_P6 is encoded by the following transcript(s): T10377 T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10377_T6 is shown in bold; this coding portion starts at position 140 and ends at position 1360. 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 lαiown or not; the presence of known SNPs in variant protein T10377_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs
Variant protein T10377_P7 according to the present invention has an amino acid sequence as given at the end ofthe application; it is encoded by transcript(s) T10377_T7. 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 protem according to the present invention to each such aligned protein is as follows:
Comparison report between T10377_P7 and Q96NF5: 1. An isolated chimeric polypeptide encoding for T10377_P7, comprising a first amino acid sequence being at least 90 % homologous to MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKE QLLDLSNGEPTRKLPQGWYGWRRSDQNQQKEMWYGWSTSQLKEEMN YIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQ SSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDK LREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYEEKLQE EQRKHSAEKEALLEETNSFLK coπesponding to amino acids 1 - 276 of Q96NF5, which also coπesponds to amino acids 1 - 276 of T10377_P7, followed by A, a second amino acid sequence being at least 90 % homologous to IEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHETEMSG ELTDSDKERYQQLEEASASLRERIRΉLDDMVΉCQQKKVKQMVEEI coπesponding to amino acids 278 - 374 of Q96NF5, which also coπesponds to amino acids 278 - 374 of T10377_P7, 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 MSHELFSRFSLRLFGR coπesponding to amino acids 375 - 390 of T10377_P7, wherein said first, A, second and third amino acid sequences are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a tail of T10377_P7, 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 MSHELFSRFSLRLFGR in T10377_P7.
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 one of the two signal- peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protem has a signal peptide.. Variant protein T10377_P7 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 T10377_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations
Variant protein T10377_P7 is encoded by the following transcript(s): T10377_T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10377_T7 is shown in bold; this coding portion starts at position 140 and ends at position 1309. 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 lαiown SNPs in variant protein T10377_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Nucleic acid SNPs
Protein T10377_P8 has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10377_T0. 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 T10377_P8 and Q96NF5: An isolated chimeric polypeptide encoding for T10377_P8, comprising a first amino acid sequence being at least 90 % homologous to
MEISLVKCSEANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYG VVRRSDQNQQKEMWYGWSTSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMRQKIR QLTQELSVSHAQQEYLENHIQTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIK DQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKL
YSQYEEKLQEEQRKHSAEKEALLEETNSFLK coπesponding to amino acids 1 - 261 of Q96NF5, which also coπesponds to amino acids 1 - 261 of T10377_P8, a second amino acid sequence comprising A, and a third amino acid sequence being at least 90 % homologous to IEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDK ERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKI SFLEGENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREINMPSRNYTPYTR VLELTMKKTLT coπesponding to amino acids 263 - 451 of Q96NF5, which also coπesponds to amino acids 263 - 451 of T10377_P8, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.
The location of the protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM: Signal peptide,NN:NO) predicts that this protein has a signal peptide.. Protein T10377_P8 also has the following non- silent SNPs (Single Nucleotide Polymoφhisms) 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 protein T10377_P8 sequence provides support for the deduced sequence of this protein according to the present invention).
Table 14 - Amino acid mutations
Protein T10377_P8 is encoded by the following transcript(s): T10377_T0, for which the sequence(s) is/are given at the end of the application The coding portion of transcript T10377_T0 is shown in bold; this coding portion starts at position 140 and ends at position 1537. 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 protein T10377_P8 sequence provides support for the deduced sequence of this protein according to the present invention). Table 15 - Nucleic acid SNPs
As noted above, cluster T 10377 features 18 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 T10377_node_0 according to the present favention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377 T0, T10377_T2, T10377_T5, T10377 T6 and T10377_T7. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
Segment cluster T10377_node_ 17 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): T10377_T0, T10377_T1, T10377_T2, T10377_T5, T10377 T6 and T10377_T7. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts
Segment cluster T10377_node_19 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): T10377_T0, T10377_T1, T10377 T2, T10377_T5, T10377_T6 and T10377_T7. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts
Segment cluster T10377_node_21 according to the present invention s supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377 T1, T10377_T2, T10377_T5, T10377_T6 and T10377_T7. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts
Segment cluster T10377_node_27 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): T10377_T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster T10377_node_33 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): T10377JTO, T10377_T1, T10377_T2, T10377_T5 and T10377_T6. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
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 T10377_node_12 according to the present invention is supported by 35 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377JT2, T10377_T5, T10377_T6 and T10377_T7. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
Segment cluster T10377_node_14 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): T10377 T0, T10377JT1, T10377 T2, T10377JT5, T10377 T6 and T10377_T7. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts
Segment cluster T10377_node_16 according to the present invention can be found in the following transcript(s): T10377_T0, T10377 T1, T10377 T2, T10377JT5, T10377_T6 and T10377_T7. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts
Segment cluster T10377_node_2 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): T10377_T1. Table 25 below describes the starting and ending position of this segment on each trans cript. Table 25 - Segment location on transcripts
Segment cluster T10377_node_23 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): T10377 T0, T10377 T1, T10377 T2, T10377_T5, T10377_T6 and T10377_T7. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts
Segment cluster T10377_node_25 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): T10377_T0, T10377_T1, T10377_T2, T10377JT5, T10377_T6 and T10377_T7. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts
Segment cluster T10377_node_29 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): T10377_T0, T10377_T1, T10377_T2 and T10377_T6. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts
Segment cluster T10377_node_3 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): T10377_T1 and T10377_T2. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts
Segment cluster T10377_node_31 according to the present invention is supported by 52 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377 T1, T10377_T2 and T10377 T5. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts
Segment cluster T10377_node_5 according to the present invention is supported by 30 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): T10377_T0, T10377_T1, T10377JT2, T10377 T5, T10377_T6 and T10377_T7. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts
Segment cluster T10377_node_8 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): T10377_T0, T10377_T1, T10377 T2, T10377_T5, T10377 T6 and T10377_T7. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts
Segment cluster T10377_node_9 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): T10377JT0, T10377_T1, T10377 T2, T10377 T5, T10377_T6 and T10377_T7. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts
Alignment of: T10377_P2 x Q96NF5 Alignment segment 1/1: Quality: 4288.00 Escore: 0 Matching length: 441 Total length: 441 Matching Percent Similarity: 99.77 Matching Percent Identity: 99.77 Total Percent Similarity: 99.77 Total Percent Identity: 99.77 Gaps : 0
Alignment : 11 ANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGV 60 1 I I I I I I I I I I I I I I I I I I I I II I I I I I II I I I II I I I I I I I 1 I I I I I I I 26 ANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGV 75 61 VRRSDQNQQKEMVVYG STSQLKEEMNYIKDVRATLEKVRKRMYGDYDEM 110 1 I I I I I I I I I I I I I I I I I I I I I II I I I 1 I I I I I I I I I I I 1 I I I 1 I I I I I I 76 VRRSDQNQQKEMVVYG STSQLKEEMNYIKDVRATLEKVRKRMYGDYDEM 125 111 RQKIRQLTQELSVSHAQQEYLENHIQTQSSALDRFNAMNSALASDSIGLQ 160 I I I I I I I I I I I I I I I I I 1 I I I I I I I I 1 II I I I I I 1 I I I I I I I I I I I I I I 1 126 RQKIRQLTQELSVSHAQQEYLENHIQTQSSALDRFNAMNSALASDSIGLQ 175 161 KTLVDVTLENSNIKDQIRNLQQTYEAΞMDKLREKQRQLEVAQVENQLLKM 210 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 1 I 1 I 1 I I I I I I I 1 I 176 KTLVDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKM 225 . . . . . 211 KVESSQEANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFL 260 I I I I I I I I I I I 1 I I I I I I 1 I I II I I I II I I 1 I I I I I I I I I I I 1 I I I I I I I 226 KVESΞQEANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFL 275 261 KAIEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHET 310 I I I 11 I 1 I I I 1 I I I I I I 1 I I 11 I I 1 II I I I I 1 I I I I I I I I I I I I I 1 I I I 276 KVIEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEHET 325 311 EMSGELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIE 360 I I I I I M I I I I I I II I I I M I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I 326 EMSGELTDΞDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIE 375 361 SLKKKLQQKQLLILQLLEKISFLEGENNELQSRLDYLTETQAKTEVETRE 410 I I I I I 1 1 I I I I I I I I I I I I 1 I I 1 1 I I I I I I I I I I 1 I I I I I I I I I I I I I I I 376 ΞLKKKLQQKQLLILQLLEKISFLEGENNELQSRLDYLTETQAKTEVETRE 425
411 IGVGCDLLPSQTGRTREIVMPSRNYTPYTRVLELTMKKTLT 451 I I I I I I I I I I I I I I I I I I I I I I I I II I 1 I I I I I I I 11 I 1 I I 426 IGVGCDLLPSQTGRTREIVMPSRNYTPYTRVLELTMKKTLT 466
Alignment of: T10377_P5 x Q96NF5
Alignment segment 1/1:
Quality: 4159.00 Escore: 0 Matching length: 438 Total length: 466 Matching Percent Similarity: 99.77 Matching Percent Identity: 99.77 Total Percent Similarity: 93.78 Total Percent Identity: 93.78 Gaps : 1
Alignment : 1 MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKK1E 50 I I I 11 II I I I II I I I I I I I I I II I I I I I 1 I) I I I I I I I I I I I I I 1 I I I I I 1 MLRSTΞTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIE 50
51 RKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYG STSQLKEE 100 I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 RKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYG STSQLKEE 100
101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 I I I I 1 I I I I I I I I I I I I I I I III I I I I I I 11 I 1 I I I I I I I I I I I I I I I I I 101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200 I I I II I I I I I I I I 1 I I I I I I I II I I I I 1 I I I I I I I I I I I I I I I I I I I I I 1 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200
201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250 1 I I I I II I I I I I I I I I II I I I I I I II II I I I I I I I I I I I I I I I I I I I I II 201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250 251 EKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEIΞLEEKDQRIG 300 I I I I I I I I I I I I I I I I I I I I I I I I II I I I 1 I I I I I I I I I I I I I I I I 11 I 251 EKLQEEQRKHSAEKEALLEETNSFLKVIEEANKKMQAAEISLEEKDQRIG 300
301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 I I I I I I I I I I I I I I I I I I I I I I I I 11 I I I I I 1 I I I I I I 1 I I I I I I I I I I I 301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 351 ERIRHLDDMVHCQQKKVKQMVE 372 I I I 1 I I I I 1 I I I I I I I I I I 1 I I 351 ERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKISFLEG 400 373 ENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNY 422 I II II I I I 11 I I I I I 1 I I I I I I I I I I 1 I II I I I I I I I I I I I I I I I I I I I I 401 ENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNY 450 423 TPYTRVLELTMKKTLT 438 I I I I I I I I 1 I 111 I I I 451 TPYTRVLELTMKKTLT 466
Alignment of: T10377_P6 x Q96NF5
Alignment segment 1/1:
Quality: 3896.00 Escore: 0 Matching length: 403 Total length: 403 Matching Percent Similarity: 99.50 Matching Percent Identity: 99.50 Total Percent Similarity: 99.50 Total Percent Identity: 99.50 Gaps : 0
Alignment :
1 MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIE 50 I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MLRSTSTVTLLSGGAARTPGAPΞRRANVCRLRLTVPPESPVPEQCEKKIE 50 51 RKEQLLDLSNGEPTRKLPQGVVYGWRRSDQNQQKEMVVYGWSTSQLKEE 100 I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 RKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGWSTSQLKEE 100 101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 1 I I I I 11 I I I I I I I I I I I I I I I I I I 1 I I I I I I 1 I I I I I I I 11 I I I I I I 11 101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200 I I I I I II I I I I 1 I I I I I 1 I I I I I I I I I I I I I I I I I I I I I 1 I I I I 1 I I I I I 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200 201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250 I I 1 I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I 201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250 . . . . . 251 EKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIG 300 I I I 1 I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I 1 I I II I I I I I I I I 251 EKLQEEQRKHSAEKEALLEETNΞFLKVIEEANKKMQAAEISLEEKDQRIG 300 301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 I I 1 I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I 1 I I I I I I I I I I I I I I II 1 301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 351 ERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKISFLEG 400 I I I 1 I I I 1 I I I I 1 I I 1 I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I 351 ERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKISFLEG 400
401 EPN 403 I I 401 ENN 403
Alignment of: T10377_P7 x Q96NF5
Alignment segment 1/1: Quality: 3642.00 Escore: 0 Matching length: 376 Total length: 376 Matching Percent Similarity: 99.47 Matching Percent Identity: 99.47 Total Percent Similarity: 99.47 Total Percent Identity: 99.47 Gaps :
Alignment : 1 MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIE 50 I I I I I I I 1 I I I I I I I I I I I I I I I I I I I 1 I I I I I I I 1 I I I I I I I 1 I 111 I 1 1 MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIE 50 51 RKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGWSTSQLKEE 100 1 I I I I I I I I I 1 I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I 1 I I I I I I I I 51 RKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYG STSQLKEE 100 101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 I I I I 1 II I 1 I I I I I I I I I I I I I I I I I I I 1 I I I I I I 1 I I I I I I I I I I I I I 1 101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200 I I I II I I I I I I I 1 I I 11 I I I I I 1 I II I I I I I I I I 1 I I I 1 I I I I I I I I I I I 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENΞNIKDQIRNLQQTYE 200 . . . . . 201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250 I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250 251 EKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIG 300 I I I 11 I I I II I I I I I I I I 1 I I I 11 I I I I I I I I I I I I I I I I I I I I I I I I I 251 EKLQEEQRKHSAEKEALLEETNSFLKVIEEANKKMQAAEISLEEKDQRIG 300 301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 I I 1 I I I I I I 1 I I I I 1 I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I 301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 351 ERIRHLDDMVHCQQKKVKQMVEEIMS 376 I I I II I I I I I I I I I I I I I I I I I I I I 351 ERIRHLDDMVHCQQKKVKQMVEEIES 376
Alignment of: T10377_P8 x Q96NF5 Alignment segment 1/1 :
Quality: 4519.00 Escore: 0 Matching length: 465 Total length: 466 Matching Percent Similarity: 99 Matching Percent Identity: 99 Total Percent Similarity: 99 Total Percent Identity: 99 Gaps : 0
Alignment :
1 MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIE 50 I I I II I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIE 50
51 RKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGWSTSQLKEE 100 I I 1 I I I I I 1 I I I I I I I I 1 I I I I II I I I I I I II I I I I I I I I I I I I I I I I I I 51 RKEQLLDLSNGEPTRKLPQGVVYG RRSDQNQQKEMVVYG STSQLKEE 100
101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150 I I 1 II I I I I I I I I I 1 I I I I I I I I I 1 I I I I I I I I I I 1 I I I I I I I I I I I I I I 101 MNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHI 150
151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200 I I I II I I I II II I I I I I 1 I I 1 I I I I I I I I I I I I 1 I 1 I I I I I I I I I 1 I I I I 151 QTQSSALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYE 200
201 ASMDKLREKQRQLEVAQVENQLLKMKVEΞSQEANAEVMREMTKKLYSQYE 250 I 11 II I I I I I 11 I I I 1 I I I II I I I 1111 I I I I I 1 I II I I I 1 I I I I I I I I I 201 ASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLYSQYE 250
251 EKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIG 300 I I I II I I I I I II I I I 1 I I I 1 I I I I I I I I I I I I II II I I I I I I I II I I I I 251 EKLQEEQRKHSAEKEALLEETNSFLKVIEEANKKMQAAEISLEEKDQRIG 300
301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 I 1 I II I I I II II I I I 1 I I I II I I I I 1 I I I I I I I II I I I I I I I I I I I I I I I 301 ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLR 350 351 ERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKI SFLEG 400 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 1 1 I I I I I I I I 1 I 351 ERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKISFLEG 400 401 ENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNY 450 I I I I I I I I I I 11 I I I II I I I I I I I I I I 1 I I I I I I I I I I I I 1 I I I I I I I I 1 401 ENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNY 450
451 TPYTRVLELTMKKTLT 466 I I I I I I I I I I I I I I I I 451 TPYTRVLELTMKKTLT 466
Expression of Q96NF5 transcripts which are detectable by amplicon as depicted in sequence name T10377 specifically in heart tissue. Expression of Q96NF5 transcripts detectable by or according to junc25-31 node(s),
T10377 amplicon(s) and T10377 junc25-31F and T10377 junc25-31R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA- amplicon), was measured similarly. For each RT sample, the expression ofthe above amplicons 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 heart samples (Sample Nos. 44, 45, 46, Table 1, above "Tissue samples in testing panel"), to obtain a value of fold up -regulation for each sample relative to median of the heart. Figure 12 is a histogram showing specific expression of the above- indicated Q96NF5 transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 12, the expression of Q96NF5 transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non- heart tissue sample Nos. 1-26,28-43 47-74 Table 1, above "Tissue samples in testing panel"). Primer pahs 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: T10377 junc25-31F forward primer; and T10377 junc25-31R 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: T10377 junc25- 31.
T10377 junc25-31F (SEQ ID NO:363): AGCAGATGGTCGAGGAGAATAATG T10377 junc25-31R (SEQ ID NO:364): ATCTCTCTGGTTTCCACTTCGG T10377 junc25-31 (SEQ ID NO:365):
AGCAGATGGTCGAGGAGAATAATGAACTACAAAGCAGGTTGGACTATTTAACAGA AACCCAGGCCAAGACCGAAGTGGAAACCAGAGAGAT
Expression of Q96NF5 transcripts detectable by or according to junc29-33 node(s), T10377 amplicon(s) and T10377 junc29-33F and T10377 junc29-33R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin- amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA- amplicon), 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 was then divided by the median of the quantities of the heart samples (Sample Nos. 44, 45, 46, Table 1, above "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the heart. Figure 13 is a histogram showing specific expression of the above-indicated Q96NF5 transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 13, the expression of Q96NF5 transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non-heart tissue sample Nos. 1-26, 28-43, 47-74 Table 1 above "Tissue samples in testing panel"). Primer pahs 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: T10377 junc29-33F forward primer; and T10377 junc29-33R 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: T10377 junc29- 33. T10377 junc29-33F (SEQ ID NO:366): CTTTCTTAGAAGGAGAGCCAAACAG T10377 junc29-33R (SEQ ID NO:367): CCTAAGTCAGAGTTTTCTTCATGGTTAAC T10377 junc29-33 (SEQ ID NO:368):
CTTTCTTAGAAGGAGAGCCAAACAGGCAGGACTCGTGAAATTGTGATGCCTTCTAG GAACTACACCCCATACACAAGAGTCCTGGAGTTAACCATGAAGAAAACTCTGACTT AGG
Expression of Q96NF5 transcripts detectable by or according to seg2-3 node(s), T10377 amplicon(s) and T10377 seg2-3F and T10377 seg2-3R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon), 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 was then divided by the median of the quantities of the heart samples (Sample Nos. 44, 45, 46, Table 1, above "Tissue samples in testing panel"), to obtain a value of fold upregulation for each sample relative to median of the heart. Figure 14 is a histogram showing specific expression of the above-indicated Q96NF5 transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 14, the expression of Q96NF5 transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in the skeletal muscle (non-heart tissue sample Nos. 1-9,13-26,28-43,47-74 Table 1, "Tissue samples in testing 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: T10377 seg2-3F forward primer; and T10377 seg2-3R reverse primer.
The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pah; for example, for the above experiment, the following amplicon was obtained as a non- limiting illustrative example only of a suitable amplicon: T10377 seg2-3. T10377 seg2-3F (SEQ ID NO:369): CTTCGCATTGTGCATAACACAA T10377 seg2-3R (SEQ ID NO:370): GAAACTCGGATACACAATCTCCAGA T10377 seg2-3 (SEQ ID NO:371): CTTCGCATTGTGCATAACACAAGCCCTGAACCAGCTGCTTTGGGAACCCCTGGGAA TAAAGTGCCCTACCTGCCTTTCAGGCACTGCCAAGCCTGGGGCATCTCTGGAGATTG TGTATCCGAGTTTC
DESCRIPTION FOR CLUSTER Z24874 Cluster Z24874 features 2 transcript(s) and 10 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
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster Z24874. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 15 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 histogram in Figure 15, concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figure 16, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression ofthe cluster in non-heart ESTs, which was found to be 16.7; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 2.1; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 3.20E-09. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 2.1, which clearly supports specific expression in heart tissue.
As noted above, cluster Z24874 έatures 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 Z24874_PEA_2_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s)
Z24874_PEA_2_T10. 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 Z24874_PEA_2_P5 and Q9NPI5: l.An isolated chimeric polypeptide encoding for Z24874_PEA_2_P5, comprising a first amino acid sequence being at least 90 % homologous to MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVTHQDDFFKPQDQIAVGEDGFKQWDVLE SLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSYKPLVDLYSR RYFLTVPYEECKWRRS coπesponding to amino acids 1 - 132 of Q9NPI5, which also coπesponds to amino acids 1 - 132 of Z24874_PEA_2_P5, 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 LPGRHEVPRGALP coπesponding to amino acids 133 - 145 of Z24874_PEA_2_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z24874_PEA_2_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%o, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LPGRHEVPRGALP in Z24874_PEA_2_P5.
Comparison report between Z24874_PEA_2_P5 and Q9NZK3: l.An isolated chimeric polypeptide encoding for Z24874_PEA_2_P5, comprising a first amino acid sequence being at least 90 % homologous to MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLE SLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSYKP coπesponding to amino acids 1 - 109 of Q9NZK3, which also coπesponds to amino acids 1 - 109 of Z24874_PEA_2_P5, 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
LVDLYSRRYFLTVPYEECKWRRSLPGRHEVPRGALP conesponding to amino acids 110 - 145 of Z24874_PEA_2_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z24874_PEA_2_P5, 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 LVDLYSRRYFLTVPYEECKWRRSLPGRHEVPRGALP in Z24874_PEA_2_P5. 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 Z24874_PEA_2_P5 is encoded by the following transcript(s): Z24874_PEA_2_T10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z24874JPEA_2_T10 is shown in bold; this coding portion starts at position 292 and ends at position 726. 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 Z24874_PEA_2_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 4 - Nucleic acid SNPs
Variant protein Z24874_PEA_2_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z24874_PEA_2_T11. 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 Z24874_PEA_2_P6 and Q9NPI5: l.An isolated chimeric polypeptide encoding for Z24874_PEA_2_P6, comprising a first amino acid sequence being at least 90 % homologous to MKLIVGIGGMTNGGKTTLTNSLLRALPNCCNIHQDDFFKPQDQIAVGEDGFKQWDVLE SLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSY conesponding to amino acids 1 - 107 of Q9NPI5, which also conesponds to amino acids 1 - 107 of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP coπesponding to amino acids 108 - 121 of Z24874_PEA_2JP6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP in Z24874_PEA_2_P6. Comparison report between Z24874_PEA_2_P6 and Q9NZK3 : l.An isolated chimeric polypeptide encoding for Z24874_PEA_2_P6, comprising a first amino acid sequence being at least 90 % homologous to MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLE SLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSY conesponding to amino acids 1 - 107 of Q9NZK3, which also coπesponds to amino acids 1 - 107 of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP coπesponding to amino acids 108 - 121 of Z24874_PEA_2_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z24874_PEA_2_P6, 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 NLPGRHEVPRGALP in Z24874_PEA_2_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: 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 Z24874_PEA_2_P6 is encoded by the following transcript(s): Z24874_PEA_2_T11, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z24874_PEA_2_T11 is shown in bold; this coding portion starts at position 292 and ends at position 654. 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 Z24874_PEA_2_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Nucleic acid SNPs
As noted above, cluster Z24874 features 10 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 Z24874_PEA_2_node_21 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): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 6 below describes the starting and ending position of this segment on each transcript. Table 6 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_4 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): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 7 below describes the starting and ending position of this segment on each transcript. Table 7 - Segment location on transcripts
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 Z24874_PEA_2_node_0 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): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 8 below describes the starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_10 according to the present invention is supported by 25 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_12 according to the present invention is supported by 26 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_13 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): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_14 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): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_16 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): Z24874_PEA_2_T10. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_3 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): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts
Segment cluster Z24874_PEA_2_node_6 according to the present invention is supported by 23 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): Z24874_PEA_2_T10 and Z24874_PEA_2_T11. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: /tmp/Ro5LG30hE3/oQvc auN J: Q9NPI5
Sequence documentation:
Alignment of: Z24874_PEA_2_P5 x Q9NPI5
Alignment segment 1/1:
Quality: 1307.00 Escore: 0 Matching length: 132 Total length: 132 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I 1 1 I I I I 1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50
51 FKQWDVLESLDMEAMLDTVQA LSSPQKFARAHGVSVQPEASDTHILLLE 100 I I I I I 1 1 I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I 51 FKQ DVLESLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLE 100
101 GFLLYSYKPLVDLYSRRYFLTVPYEECKWRRS 132 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I 101 GFLLYSYKPLVDLYSRRYFLTVPYEECK RRS 132
Sequence name: /tmp/Ro5LG30hE3/oQvcWauN J:Q9NZK3
Sequence documentation:
Alignment of: Z24874 PEA 2 P5 x Q9NZK3
Alignment segment 1/1:
Quality: 1070.00 Escore 0 Matching length: 109 Total length 109 Matching Percent Similarity: 100.00 Matching Percent Identity 100.00 Total Percent Similarity: 100.00 Total Percent Identity 100.00 Gaps : 0
Alignment :
1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50
51 FKQ DVLEΞLDMEAMLDTVQA LSSPQKFARAHGVSVQPEASDTHILLLE 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I 51 FKQWDVLESLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLE 100
101 GFLLYSYKP 109 I I 11 I I I I I 101 GFLLYSYKP 109
Sequence name: /tmp/TxcClAWX3r/LIzBcJ0ujT:Q9NPI5
Sequence documentation: Alignment of: Z24874_PEA_2_P6 x Q9NPI5
Alignment segment 1/1:
Quality: 1048.00 Escore: 0 Matching length: 107 Total length: 107 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
1 MKL1VGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50 I I I I I I I I I I I I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I 1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50
51 FKQ DVLESLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLE 100 I I I I I 1 I I I I I I I I I I 1 I I I I I I I 1 I 1 I I I I I I IH I I I I I I I I I I I I 1 I I 51 FKQWDVLESLDMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLE 100
101 GFLLYSY 107 I I I I I 1 I 101 GFLLYSY 107
Sequence name: /tmp/TxcClAWX3r/LIzBcJ0ujT :Q9NZK3
Sequence documentation:
Alignment of: Z24874_PEA_2 P6 x Q9NZK3
Alignment segment 1/1:
Quality: 1048.00 Escore: 0 Matching length: 107 Total length: 107 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0 Alignment :
1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50 I I I I I I I I I I I I I I I I ) I I I I I I I I I I I 1 I I I I 1 I I I I I I I I I I I I I I I I 1 MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDG 50
51 FKQ DVLESLDMEAMLDTVQA LSSPQKFARAHGVSVQPEASDTHILLLE 100 I I I I I I I I I 1 I I I I I I I I I I I I I I I 1 I 1 I I I I I I I I I 1 1 I I I I I I I I I I I 51 FKQWDVLESLDMEAMLDTVQA LSSPQKFARAHGVSVQPEASDTHILLLE 100
101 GFLLYSY 107 I I I I I I I 101 GFLLYSY 107
DESCRIPTION FOR CLUSTER HUMCDDANF Cluster HUMCDDANF 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
Table 3 - Proteins of interest
These sequences are variants of the known protein Atrial natriuretic factor precursor (SwissProt accession identifier ANFJHUMAN; known also according to the synonyms ANF; Atrial natriuretic peptide; ANP; Prepronatriodilatin), refeπed to herein as the previously knovra protem; it contains Cardiodilatin-related peptide (CDP). Protein Atrial natriuretic factor precursor is known or believed to have the following function(s): Atrial natriuretic factor (ANF) is a potent vasoactive substance synthesized in mammalian atria and is thought to play a key role in cardiovascular homeostasis; has a cGMP- stimulating activity. The sequence for protein Atrial natriuretic factor precursor is given at the end of the application, as "Atrial natriuretic factor precursor amino acid sequence" (SEQ ID NO:350). Known polymoφhisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein
Protein Atrial natriuretic factor precursor localization is believed to be Secreted. 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 lαiown protein are as follows: Aldosterone antagonist; Diuretic; Electrolyte absoφtion 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: Antihypertensive, diuretic; Antiasthma; Urological; Cardiostimulant, Antianaemic, Cardiovascular, Neuroprotective, Fertility enhancer, Male contraceptive, Hypolipaemic/Antiatherosclerosis, Hepatoprotective and renal failure. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: physiological processes; blood pressure regulation, which are annotation(s) related to Biological Process; hormone activity, 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/>.
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster HUMCDDANF. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the yaxis of Figure 17A 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 histogram in Figure 17A, concerning the number of heart-specific clones in libraries/sequences; as well as with regard to the histogram in Figure 17B, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs was found to be 56.3; The expression levels of this gene in muscle was negligible; and fisher exact test P- values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 1.20E-249. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the expression levels of this gene in muscle was negligible, which clearly supports specific expression in heart tissue. As noted above, cluster HUMCDDANF features 2 transcript(s), which were listed in
Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Atrial natriuretic factor precursor. A description of each variant protein accordmg to the present invention is now provided. Variant protein HUMCDDANF_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCDDANF_T3. An alignment is given to the known protein (Atrial natriuretic factor 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 HUMCDDANF_P2 and ANF_HUMAN: l.An isolated chimeric polypeptide encoding for HUMCDDANF_P2, comprising a first amino acid sequence being at least 90 % homologous to MPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRGPWDSSDRS ALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY conesponding to amino acids 51 - 151 of ANF_HUMAN, which also coπesponds to amino acids 1 - 101 of HUMCDDANF_P2. 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 intracellular 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 HUMCDDANF_P2 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HUMCDDANF_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations
Variant protein HUMCDDANF_P2 is encoded by the following transcript(s): HUMCDDANF_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCDDANF_T3 is shown in bold; this coding portion starts at position 381 and ends at position 683. 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 HUMCDDANF_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs
Variant protein HUMCDDANF_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCDDANF_T4. An alignment is given to the known protein (Atrial natriuretic factor 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 ofthe variant protein according to the present invention to each such aligned protein is as follows:
Comparison report between HUMCDDANF_P3 and ANF_HUMAN: l.An isolated chimeric polypeptide encoding for HUMCDDANF_P3, 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 MSSFSTTT coπesponding to amino a:ids 1 - 8 of HUMCDDANF_P3, and a second amino acid sequence being at least 90 % homologous to NLLDHLEEKMPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGR GPWDSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY coπesponding to amino acids 42 - 151 of ANF_F1LJMAN, which also conesponds to amino acids 9 - 118 of HUMCDDANF_P3, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of HUMCDDANF_P3, comprising a polypeptide being at feast 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 MSSFSTTT of HUMCDDANF_P3
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 HUMCDDANF P3 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HUMCDDANF_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations
Variant protein HUMCDDANF_P3 is encoded by the following transcript(s): HUMCDDANF_T4, for which the sequence(s) is/are gven at the end of the application. The coding portion of transcript HUMCDDANF_T4 is shown in bold; this coding portion starts at position 104 and ends at position 457. 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 HUMCDDANF_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs
224
Variant protein HUMCDDANF_P3 is encoded by the following transcπpt(s) HUMCDDANF T4, for which the sequence(s) is/are gven at the end of the application The coding portion of transcript HUMCDDANF T4 is shown in bold, this coding portion starts at position 104 and ends at position 457 The transcnpt 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 HUMCDDANF_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention) Table 10 - Nucleic acid SNPs
225
As noted above, cluster HUMCDDANF 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 HUMCDDANF_node_0 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): HUMCDDANF T3. Table 1 1 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts
Segment cluster HUMCDDANF_node_10 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): HUMCDDANF T3 and HUMCDDANF T4. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts
Segment cluster HUMCDDANF_node_2 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): HUMCDDANF_T4. Table 13 below describes the starting and ending position of this segment on each transcript. 226
Segment cluster HUMCDDANF_node_5 according to the present invention is supported by 62 libraπes. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCDDANF_T3 and HUMCDDANF_T4. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts
Segment cluster HUMCDDANF_node_8 according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCDDANF T3 and HUMCDDANF T4. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts
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. 227 Segment cluster HUMCDDANF node l 1 according to the present invention can be found in the following transcript(s): HUMCDDANF T3 and HUMCDDANF T4. Table 16 below describes the starting and ending position of this segment on each transcnpt. Table 16 - Segment location on transcripts
Segment cluster HUMCDDANF_node_12 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): HUMCDDANF T3 and HUMCDDANF T4. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: /tmp/3GyιZQyJ8L/:) Yng3zFfcE : ANF_HUMAN
Sequence documentation:
Alignment of: HUMCDDANF_P2 x ANF_HUMAN Alignment segment 1/1:
Quality: 988.00 Escore: 0 Matching length: 101 Total length: 101 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 228
Alignment :
1 MPLEDEWPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRG 50 I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I 51 MPLEDEWPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRG 100
51 PWDSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNSFR 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 PWDSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNSFR 150
101 Y 101 I 151 Y 151
Sequence name: /tmp/mnb70PVCPP/oTrSwgJLyB: ANF_HUMAN
Sequence documentation:
Alignment of: HUMCDDANF_P3 x ANF_HUMAN
Alignment segment 1/1:
Quality: 1076.00 Escore: 0 Matching length: 110 Total length: 110 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment:
9 NLLDHLEEKMPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQ 58 I I I I I I I I I I I I II I I I I I I I I I I I I I II II I I I I II I II I I I I I I I I I I 42 NLLDHLEEKMPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQ 91
59 RDGGALGRGP DSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQ 108 I I I I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 92 RDGGALGRGP DSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQ 141 22 9
1 0 9 SGLGCNS FRY 1 18 I I I I I I I I I I 142 SGLGCNS FRY 1 51 Expression of Human cardiodilatin-atrial natriuretic factor (CDD-ANF) HUMCDDANF transcripts which are detectable by amplicon as depicted in sequence name HUMCDDANFjunc2-5F2R2 specifically in heart tissue Expression of Human cardiodilatin-atrial natriuretic factor (CDD-ANF) transcripts detectable by or according to junc2-5 node(s), HUMCDDANFjunc2-5F2R2 amplicon and primers HUMCDDANFjunc2-5F2 HUMCDDANFjunc2-5R2 was measured by real time PCR (this transcript relates to the known or WT protein). In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM 000981 ; RPL19 amplicon), TATA box (GenBank Accession No. NM 003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM 004168; amplicon- SDHA- amplicon) 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 was then divided by the quantity of heart sample no. 45 (Table 1, above), to obtain a value of relative expression for each sample relative to this heart sample. As is evident from Figure 18, the expression of Human cardiodilatin-atrial natriuretic factor (CDD-ANF) transcripts detectable by the above amplicon(s) in one of the heart tissue samples (Sample Nos. 45, Table 1, "Tissue samples in testing panel") was significantly higher than in the other samples, including other two heart samples. Sample 45 is from fibrotic heart, as opposed to heart samples 44 and 46 that are from normal hearts. (Note - the product in samples 10 and 11 was found to be a non-specific product by inspecting the dissociation curve that was created in the real-time PCR 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: HUMCDDANFjunc2-5F2 forward primer; and HUMCDDANFjunc2-5R2 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 230 was obtained as a non- limiting illustrative example only of a suitable amplicon: HUMCDDANFjunc2-5F2R2. Forward primer HUMCDDANFjunc2-5F2 (SEQ ID NO:374): CTTCTCCACCACCACCAATTTG Reverse primer HUMCDDANFjunc2-5R2 (SEQ ID NO:375): GAGAGCAGCCCCCGCT Amplicon HUMCDDANFjunc2-5F2R2 (SEQ ID NO:376): CTTCTCCACCACCACCAATTTGCTGGACCATTTGGAAGAAAAGATGCCTTTAGAAG ATGAGGTCGTGCCCCCACAAGTGCTCAGTGAGCCGAATGAAGAAGCGGGGGCTGCT CTC
DESCRIPTION FOR CLUSTER HUMTROPIA Cluster HUMTROPIA features 4 transcript(s) and 20 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
Table 2 - Segments of interest
231
Table 3 - Proteins of interest
These sequences are variants of the known protein Troponin I, cardiac muscle (SwissProt accession identifier TRIC HUMAN), refeπed to herein as the previously known protein and shown as SEQ ID NO: 351.
Protein Troponin I, cardiac muscle is known or believed to have the following 232 function(s): Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium- sensitivity to striated muscle actomyosin ATPase activity. Troponin I, cardiac muscle Binds to actin and tropomyosin. Defects in Troponin I, cardiac muscle are the cause of familial hypertrophic cardiomyopathy type 7 (CMH7) [MIM.191044]; also known as FHC type 7. CMH7 is an autosomal dominant disorder characterized by increased myocardial mass with myocyte and myofibrillar disaπay. Defects in Troponin I, cardiac muscle are the cause of familial restrictive cardiomyopathy (RCM) [MIM:115210]. RCM is a heart muscle disorder characterized by impaired filling of the ventricles with reduced volume in the presence of normal or near normal wall thickness and systolic function. The disease may be associated with systemic disease but is most often idiopathic. The sequence for protein Troponin I, cardiac muscle is given at the end of he application, as "Troponin I, cardiac muscle amino acid sequence" (SEQ ID NO:351). Known polymoφhisms for this sequence are as shown in Table 4.
Table 4 - Amino acid mutations for Known Protein
In addition to the above known polymoφhisms, the present inventors have uncovered two new additional SNPs (shown with regard to SEQ ID NO:352 for the resultant amino acid sequence, and SEQ ID NO:353 for the nucleic acid sequence). This SNP is C-> (missing 233 nucleotide "C"; will affect amino acid residues from 167 onwards). This will create a frame shift. A new protein will be formed. However, this SNP was located in a stretch of cytosine residues, which are known to be prone to errors in sequencing. The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer, lung, non-small cell; Cancer, breast; Cancer, sarcoma. 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: Angiogenesis inhibitor; Epidermal growth factor antagonist; Fibroblast growth factor receptor antagonist. 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: Ophthalmological; Anticancer. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: control of heart, which are annotation(s) related to Biological Process; and troponin complex, 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/>.
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster HUMTROPIA. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the yaxis of Figure 19 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 histogram in Figure 19, concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figure 20, concerning the actual expression of oligonucleotides in 234 various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 27.5. The expression level of this gene in muscle was negligible; and fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 2.10E-88. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the expression level of this gene in muscle was negligible which clearly supports specific expression in heart tissue. As noted above, cluster HUMTROPIA features 4 transcript(s), which were listed in Table
1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Troponin I, cardiac muscle. A description of each variant protein according to the present invention is now provided. Variant protein HUMTROPIA_PEA_2_P5 according b the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMTROPIA_PEA_2_T3. An alignment is given to the known protein (Troponin I, cardiac muscle) 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 HUMTROPIA_PEA_2_P5 and TRIC_HUMAN: l.An isolated chimeric polypeptide encoding for HUMTROPIA PEA 2 P5, comprising a first amino acid sequence being at least 90 % homologous to MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQ ELEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAK 235
VTKN1TE corresponding to amino acids 1 - 124 of TRIC HUMAN, which also coπesponds to amino acids 1 - 124 of HUMTROPIA PEA 2 P5, 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 VGRMGSSGTFGVG conesponding to amino acids 125- 137 of HUMTROPIA_PEA_2_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMTROPIA PEA 2 P5, 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 VGRMGSSGTFGVG in HUMTROPIA_PEA_2_P5.
The cellular 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 intracellular 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 HUMTROPIA_PEA_2_P5 is encoded by the following transcript(s): HUMTROPIA_PEA_2_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMTROPIA_PEA_2_T3 is shown in bold; this coding portion starts at position 148 and ends at position 558. Variant protein HUMTROPIA PEA 2 P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMTROPIA PEA 2 T15. An alignment is given to the known protein (Troponin I, cardiac muscle) 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 HUMTROPIA_PEA_2_P12 and TRIC_HUMAN: 236 l .An isolated chimeric polypeptide encoding for HUMTROPIA_PEA_2_P12, comprising a first amino acid sequence being at least 90 % homologous to MADGSSDA conesponding to amino acids 1 - 8 of TRIC_HUMAN, which also conesponds to amino acids 1 - 8 of
HUMTROPIA PEA 2 P12, 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 bast
95%o homologous to a polypeptide having the sequence
KKSKISASRKLQLKTLLLQIAKQELEREAEERRGEKGRALSTRCQPLELAGL
GFAELQDLCRQLHARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTLRRV
RISADAMMQALLGARAKESLDLRAHLKQVKKEDTEKENREVGDWRKNIDALSGMEG RKKKFES coπesponding to amino acids 36 - 209 of TRIC HUMAN, which also coπesponding to amino acids 9 - 182 of HUMTROPIA PE A_2_P 12, 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 HUMTROPIA_PEA_2_P12, 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 AK, having a structure as follows: a sequence starting from any of amino acid numbers 8-x to 8; and ending at any of amino acid numbers 9+ ((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: intracellularly. The protein localization is believed to be intracellular 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 HUMTROPIA_PEA_2_P12 is encoded by the following transcript(s):
HUMTROPIA_PEA_2_T15, for which the sequence(s) is/are given at the end of the 237 application. The coding portion of transcript HUMTROPIA PEA 2 T15 is shown in bold; this coding portion starts at position 148 and ends at position 693. Variant protein HUMTROPIA PEA 2 P17 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s)
HUMTROPIA PEA 2 T7. An alignment is given to the known protein (Troponin I, cardiac muscle) 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 HUMTROPI A PE A_2_P 17 and TRIC HUMAN: l.An isolated chimeric polypeptide encoding for HUMTROPIA PEA 2 P17, comprising a first amino acid sequence being at least 90 % homologous to MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAK coπesponding to amino acids 1 - 36 of TRIC HUMAN, which also coπesponds to amino acids 1 - 36 of HUMTROPIA PEA 2 P17, 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%o homologous to a polypeptide having the sequence
VGRGFLGAEYRRRRDPRPWEWGEEPGLRRGRGLRGGASGAEFCRGSCSDW coπesponding to amino acids 37- 86 of HUMTROPIA_PEA_2_P17, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMTROPIA PEA 2 P17, 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 VGRGFLGAEYRRRRDPRPWEWGEEPGLRRGRGLRGGASGAEFCRGSCSDW in HUMTROPIA_PEA_2_P17.
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 intracellular because neither of the 238 trans- embrane region prediction programs predicted a trans- embrane region for this protein.
In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.. Variant protein HUMTROPIA PEA 2 P17 is encoded by the following transcript(s): HUMTROPIA PEA 2 T7, for which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HUMTROPIA_PEA_2_T7 is shown in bold; this coding portion starts at position 148 and ends at position 405. Variant protein HUMTROPIA PEA 2 P18 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMTROPIA PEA 2 T10. An alignment is given to the known protein (Troponin I, cardiac muscle) 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 HUMTROPIA PEA 2 P18 and TRIC HUMAN: l .An isolated chimeric polypeptide encoding for HUMTROPIA_PEA_2_P18, comprising a first amino acid sequence being at least 90 % homologous to MADGSSDA coπesponding to amino acids 1 - 8 of TRIC HUMAN, which also conesponds to amino acids 1 - 8 of HUMTROPIA_PEA_2_P18, and a second amino acid sequence being at least 70%, optionally at least 80%o, preferably at least 85%, more preferably at least 90%> and most preferably at least 95% homologous to a polypeptide having the sequence VRAAG coπesponding to amino acids 9- 13 of HUMTROPIA_PEA_2_P18, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a tail of HUMTROPIA PEA 2 P18, 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 VRAAG in HUMTROPIA_PEA_2_P18. 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 239 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- embrane 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 HUMTROPIA PEA 2 P18 is encoded by the following transcript(s): HUMTROPIA_PEA_2_T10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMTROPIA_PEA_2_T10 is shown in bold; this coding portion starts at position 148 and ends at position 186. As noted above, cluster HUMTROPIA features 20 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 HUMTROPIA_PEA_2_node_0 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): HUMTROPIA_PEA_2_T10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7. Table 7 below describes the starting and ending position of this segment on each transcript. Table 7 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_10 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This 240 segment can be fnind in the following tιanscπpt(s) HUMTROPIA_PEA_2_T7 Table 8 below describes the starting and ending position of this segment on each transcript Table 8 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_22 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 transcnpt(s) HUMTROPIA PEA 2 T3 Table 9 below describes the starting and ending position of this segment on each transcπpt Table 9 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_23 according to the present invention is supported by 49 hbranes The number of hbranes was determined as previously descπbed This segment can be found in the followmg transcπpt(s) HUMTROPIA_PEA_2_T10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7 Table 10 below describes the startmg and endmg position of this segment on each transcript Table 10 - Segment location on transcripts
24 1 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 HUMTROPIA_PEA_2_node_l 1 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): HUMTROPIA_PEA_2_T10, HUMTROPIA PEA 2 T15, HUMTROPIA PEA 2 T3 and HUMTROPIA PEA 2 T7. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_14 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): HUMTROPIA PEA 2 T10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts
242 Segment cluster HUMTROPIA_PEA_2_node_15 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): HUMTROPI A PEA 2 T 10, HUMTROPIA PEA 2 T15, HUMTROPI AJΕA 2 T3 and HUMTROPIA PEA 2 T7. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts
Segment cluster HUMTROPI A_PEA_2_node_ 16 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): HUMTROPI A PEA 2 T 10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_20 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): HUMTROPI A_PEA_2_T 10, HUMTROPIA PEA 2 T15, HUMTROPIA PEA 2 T3 and HUMTROPIA PEA 2 T7. Table 243 15 below describes the starting and ending position of this segment on each transcπpt. Table 15 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_21 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): HUMTROPI A_PEA_2_T 10, HUMTROPIA PEA 2 T15, HUMTROPIA PEA 2 T3 and HUMTROPIA_PEA_2_T7. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_24 according to the present invention can be found in the following transcript(s): HUMTROPIA_PEA_2_T10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts
244
Segment cluster HUMTROPIA_PEA_2_node_25 according to the present invention can be found in the following transcript(s): HUMTROPIA PEA 2 T 10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_29 according to the present invention can be found in the following transcript(s): HUMTROPIA PEA 2 T10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA_PEA_2_T7. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts
24 5 Segment cluster HUMTROPIA_PEA_2_node_30 according to the present invention can be found in the following transcript(s): HUMTROPIA PE A_2_T 10, HUMTROPIA PEA 2 T15, HUMTROPIA_PEA_2_T3 and HUMTROPIA PEA 2 T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster HUMTROPI A_PEA_2_node_31 according to the present invention can be found in the following transcript(s): HUMTROPIA PEA 2 T 10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPI A_PEA_2_T7. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_32 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): HUMTROPIA_PEA_2_T10, HUMTROPIA_PEA_2_T15, HUMTROPIA_PEA_2_T3 and HUMTROPI A_PEA_2_T7. Table 22 below describes the starting and ending position of this segment on each transcript. 24 6 Table 22 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_4 according to the present invention can be found the following transcript(s): HUMTROPIA PEA 2 T10, HUMTROPIA PEA 2 T15, HUMTROPI A PEA 2 T3 and HUMTROPIA PEA 2 T7. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_5 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): HUMTROPIA PEA 2 T10. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts
247 Segment cluster HUMTROPIA_PEA_2_node_8 according to the present invention is supported by 27 libraries. The number of libraries was detennined as previously descπbed. This segment can be found in the following transcript(s)- HUMTROPIA_PEA_2_T10, HUMTROPIA_PEA_2_T3 and HUMTROPIA PEA 2 T7. Table 25 below describes the starting and ending position of this segment on each transcπpt. Table 25 - Segment location on transcripts
Segment cluster HUMTROPIA_PEA_2_node_9 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): HUMTROPIA_PEA_2_T10, HUMTROPI A PEA 2 T3 and HUMTROPIA_PEA_2_T7. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: /tmp/p5CHmauP3N/NVyK804uFt :TRIC_HUMAN Sequence documentation:
Alignment of: HUMTR0PIA_PEA_2_P5 x TRIC_HUMAN 248
Alignment segment 1/1:
Quality: 1183.00 Escore: 0 Matching Jength: 124 Total length: 124 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.19 Total Percent Similarity: 100.00 Total Percent Identity: 99.19 Gaps : 0
Alignment:
2 ADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKT 51 I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 ADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKT 50
52 LLLQIAKQELEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLH 101 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I 1 I I I I I I I I I I 1 I I I I I I I 51 LLLQIAKQELEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLH 100 102 ARVDKVDEERYDIEAKVTKNITEV 125 I I I I I I I I I I I I I I II I I II I I I : 101 ARVDKVDEERYDIEAKVTKNITEI 124
Sequence name: /tmp/gCDnOSmn31/GzfEmz5N5Z : RIC_HUMAN
Sequence documentation:
Alignment of: HUMTROPIA_PEA_2_P12 x TRIC_HUMAN
Alignment segment 1/1:
Alignment :
Quality: 873.00 Length: 209 Ratio: 4.823 Gaps: 1 Percent Similarity: 86.603 Percent Identity: 86.603 alignment block: 24 9 HUMTROPIA_PEA_2_P 12 x Troponi n
Al ign seg 1 / 1 to : Troponin from : 1 to : 209 2 ADGSSDA KKSKI SASRKLQLKT 23 I I I I I I I I I I I I I I I I I I I I I I 1 ADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKT 50
24 LLLQIAKQELEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLH 73 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 LLLQIAKQELEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLH 100
74 ARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTLRRVRISA 123 I I I 11 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 ARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTLRRVRISA 150
124 DAMMQALLGARAKESLDLRAHLKQVKKEDTEKENREVGDWRKNIDALSGM 173 I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 DAMMQALLGARAKESLDLRAHLKQVKKEDTEKENREVGDWRKNIDALSGM 200
174 EGRKKKFES 182 I I I I I I I I I 201 EGRKKKFES 209
Sequence name: /tmp/08saIrM011/UUlNos] zB3 : TRIC_HUMAN
Sequence documentation:
Alignment of: HUMTROPIA_PEA_2_P17 x TRIC_HUMAN
Alignment segment 1/1:
Quality: 344.00 Escore: 0 Matching length: 35 Total length: 35 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0 250 Alignment :
2 ADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAK 36 I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 ADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAK 35
Sequence name: /tmp/shMGxspSCh/hLCzvaPT2] : TRIC_HUMAN
Sequence documentation:
Alignment of: HUMTROPIA_PEA_2_P18 x TRIC_HUMAN
Alignment segment 1/1:
Quality: 71.00 Escore: 0 Matching length: 9 Total length: 9 Matching Percent Similarity: 88.89 Matching Percent Identity: 88.89 Total Percent Similarity: 88.89 Total Percent Identity: 88.89 Gaps: 0
Alignment :
2 ADGSSDAVR 10 I I I I I I I I 1 ADGSSDAAR 9
Expression of TRIC HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts which are detectable by amplicon as depicted in sequence name HUMTROPIA seg 10 specifically in heart tissue Expression of TRIC_HUMAN Troponin I, cardiac muscle transcripts detectable by or according to seglO node(s), HUMTROPIA seglO amplicon(s) and HUMTROPIA seglOF2 and
HUMTROPIA seglOR2 primers was measured by real time PCR. In parallel the expression of four housekeeping genes -Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM 004168; amplicon - SDHA- 251 amplicon), RPL19 (GenBank Accession No. NM 000981 ; RPL19 amplicon), TATA box (GenBank Accession No. NM 003194; TATA amplicon) was measured similarly. For each RT sample, the expression of the above amplicons was noπnalized 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 heart samples (Sample Nos. 44-46, Table 1 , above"Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the heart. Figure 21A is a histogram showing specific expression of the above- indicated TRIC_HUMAN Troponin I, cardiac muscle transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 21 A, the expression of TRIC HUMAN Troponin I, cardiac muscle transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in most other samples (non-heart tissue sample Nos. 1-9,1 1-26, 28-43, 47-74 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 pah was used as a non- limiting illustrative example only of a suitable primer pair: HUMTROPIA seglOF2 forward primer; and HUMTROPIA seglOR2 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: HUMTROPIA seglO. HUMTROPIA segl Forward primer (SEQ ID NO:377): TTGCAGAGGGTCATGCTCG HUMTROPIA segl Reverse primer (SEQ ID NO:378): TCCTTTGGATAGGCACTTCCC HUMTROPIA segl Amplicon (SEQ ID NO:379):
TTGCAGAGGGTCATGCTCGGATTGGTGACAGCAGCCTGCGGGCGGAACTCCGTTGC CCTCGGACTTGCTTAGGGATAGATGGGAAGTGCCTATCCAAAGGA Expression TRIC HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts,which are detectable by amplicon as depicted in sequence name HUMTROPIA seg22 specifically in heart 252 tissue Expression of TRIC_HUMAN Troponin I, cardiac muscle transcripts detectable by or according to seg22 node(s), HUMTROPIA seg22 amplicon(s) and HUMTROPIA seg22F and HUMTROPIA seg22R primers was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981 ; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM 004168; amplicon - SDHA- amplicon), was measured similarly. For each RT sample, the expression of the above amplicons was normalized to the geometric mean ofthe quantities of the housekeeping genes. The noπnalized quantity of each RT sample was then divided by the median of the quantities of the heart samples (Sample Nos. 44-46, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the heart. Figure 21B is a histogram showing specific expression of the above -indicated TRIC HUMAN Troponin 1, cardiac muscle transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 2 IB, the expression of TRIC HUMAN Troponin I, cardiac muscle transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in the other samples (non-heart tissue sample Nos. 1-43, 47-74 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: HUMTROPIA seg22F forward primer; and HUMTROPIA seg22R 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: HUMTROPIA seg22. HUMTROPIA seg22 Forward primer (SEQ ID NO:380): GTGGGACGCATGGGCA HUMTROPIA seg22 Reverse primer (SEQ ID NO:381): TTGTCCTGGGTCTCCTGGG HUMTROPIA seg22 Amplicon (SEQ ID NO:382):
GTGGGACGCATGGGCAGCTCGGGTACCTTCGGGGTAGGGTGAGATGGCTGGGACTT 253
GGTCTCTGCCTGACCCCTTGCAGCTGCTTTTGGCTGCACATCCCAGGAGACCCAGGA CAA
Expression of TRIC HUMAN Troponin I, cardiac muscle HUMTROPIA transcripts which are detectable by amplicon as depicted in sequence name HUMTROPIA seg23-24-25 specifically in heart tissue Expression of TRIC_HUMAN Troponin I, cardiac muscle transcripts detectable by or according to seg23-24-25 node(s), HUMTROPIA seg23-24-25 amplicon(s) and primers
HUMTROPIA seg23-24-25F and HUMTROPIA seg23-24-25R was measured by real time PCR. This transcript relates to the known or WT protein (SEQ ID NO:351). In parallel the expression of four housekeeping genes - RPL19 (GenBank Accession No. NM_000981 ; RPL19 amplicon), TATA box (GenBank Accession No. NM 003194; TATA amplicon), Ubiquitin
(GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank
Accession No. NM_004168; amplicon - SDHA-amplicon) 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 was then divided by the median of the quantities of the heart samples (Sample Nos. 44-46 Table 1, above), to obtain a value of relative expression for each sample relative to median of the heart samples. Figure 22 is a histogram showing relative expression of the above- indicated
TRIC_HUMAN Troponin I, cardiac muscle transcripts in heart tissue samples as opposed to other tissues. As is evident from Figure 22, the expression of TRIC HUMAN Troponin I, cardiac muscle transcripts detectable by the above amplicon(s) in heart tissue samples was significantly higher than in the other samples (Sample Nos. 44-46 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: HUMTROPIA seg23-24-25F forward primer; and HUMTROPIA seg23-24-25FR reverse primer. The present invention also preferably encompasses any amplicon obtained through the 254 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: HUMTROPIA seg23-24-25. Forward primer HUMTROPIA seg23-24-25F (SEQ ID NO:383): AAGATCTTTGACCTTCGAGGCA Reverse primer HUMTROPIA seg23-24-25R (SEQ ID NO:384): CTGCTTGAGGTGGGCCC Amplicon HUMTROPIA seg23-24-25 (SEQ ID NO:385): AAGATCTTTGACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGAT CTCTGC AG ATGCC ATG ATGC AGGCGCTGCTGGGGGCCCGGGCTAAGG AGTCCCTGG ACCTGCGGGCCCACCTCAAGCAG
ADDITIONAL INFORMATION - VARIANT ORFS With regard to the variants of this cluster, the following should be noted. Sequence T7
(also refened to herein as HUMTROPIA_PEA_2_T7 and troponin T7) has three open reading frames (ORFs) which are described in greater detail below.
The sequence in SEQ ID NO: 354 shows CDS- 1 frame 1 from 148 to 406 length 259 (bp) = 86 (aa)(similar to Troponin I N-ter)
MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKVGRGFLGAEYRRRRDPRPWEW GEEPGLRRGRGLRGGASGAEFCRGSCSDW*
The sequence in SEQ ID NO: 355 shows CDS-2 frame 1 from 628 to 1183 bngth 556 (bp) = 185 (aa) (similar to Troponin I C-terminal portion)
MILPCSISPWQKKSKISASRKLQLKTLLLQIAKQELEREAEERRGEKGRALSTRCQPLEL AGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTL RRVRISADAMMQALLGARAKESLDLRAHLKQVKKEDTEKENREVGDWRKNIDALSG MEGRKKKFES*
The sequence in SEQ ID NO: 356 shows CDS-3 frame 2 from 155 to 629 length 475 (bp) = 158 (aa)(Not similar to Troponin I) MGAAMRLGNLALHQPQSDAAPPTTALMPRSRTPRWDGASWGQSTGAGGIQDPGSGG 255
RSQGCEGGGDYAEGLQGRSFAEGHARIGDSSLRAELRCPRTCLGIDGKCLSKGRDPDW WMGMRGVASRRLRAQVGRGPKSGPAGFAGGVLRSPPPSSPNPPP*
However, the presence of three ORFs could potentially complicate expression and also determination of expression of the desired protein. The first ORF starts at +1 of Troponin sequence (first "ATG" is +1 to +3), and the second ORF starts at +8, encoding a 158 amino acid protein. Since the 2nd ATG is located very close to the first one, there is a possibility that it will be expressed as well. In order to eliminate this possibility of expression of the long ORF, it is possibfe to optionally introduce two mutations (shown with regard to Figure 33): 1. "c" at position 57 to "a" 2. "g" at position 111 to "a" Both mutations are silent, so the protein sequence will not change.
Cloning and expression verification of a Troponin variant HUMTROPIA PEA 2 T7 was performed as follows.
1. Full length validation 1.1. RNA preparation Human adult normal heart RNA pool (lot# A411077) was obtained from BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com). Total RNA samples were treated with DNasel (Ambion Cat # 1906). 1.2. RT PCR Purified RNA (1 ug) was mixed with 150 ng Random Hexamer primers (Invitrogen Cat # 48190-011 ) and 500 uM dNTP (Takara, Cat # B9501- 1) in a total volume of 15.6ul DEPC- H20 (Beit Haemek, Cat # 01-852- 1 A). The mixture was incubated for 5 min at 65°C and then quickly chilled on ice. Thereafter, 5 ul of 5X Superscriptll first strand buffer (Invitrogen, Cat # Y00146), 2.4ul 0.1M DTT (Invitrogen, Cat #Y00147) and 40 units RNasin (Promega, Cat # N251A) were added, and the mixture was incubated for 2 min at 42°C. Then, 1 ul (200units) of Superscriptll (Invitrogen, Cat #18064-022) was added and the reaction was incubated for 50 256 min at 42°C and then inactivated at 70°C for 15min. The resulting cDNA was diluted 1 :20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8). 1.3. RT-PCR analysis cDNA (5ul), prepared as described above, was used as a template in PCR reactions. The amplification was done using AccuPower PCR PreMix (Bioneer, Korea, Cat# K2016), under the following conditions: lul - of each primer (lOuM) Tropfor (SEQ ID NO: 357) CCCTCACTGACCCTCCAAAC TropRev (SEQ ID NO: 358) CTTCCCATCTATCCCTAAGC plus 13ul - H20 were added into AccuPower PCR PreMix tube with a reaction program of 5 minutes at 94°C; 29 cycles of: [30 seconds at 94°C, 30 seconds at 52°C, 40 seconds at 72°C] and 10 minutes at 72°C. At the end of the PCR amplification, products were analyzed on agarose gels stained with ethidium bromide and visualized with UV light. PCR product was extracted from the gel using QiaQuick™ gel extraction kit (Qiagen™, Cat #28706). The extracted DNA product then served as a template for secondary PCR reaction under the following conditions. 5fll - Amplification XI 0 buffer (Invitrogen Cat # 11708021); 10ul - purified DNA; l - dNTPs (lOmM each); lul MgS04 (50mM) 5μl enhancer solution (Invitrogen, Cat # 11708021); 1 ul - of each primer ( I OuM); 26ul - H20 and 1.25 units of Taq polymerase [Platinum Pfx DNA polymerase (Invitrogen, Cat# 11708021)] in a total reaction volume of 50ul. Amplification was performed with an initial denaturation step at 94°C for 3 minutes followed by 29 cycles of [94°C for 30 seconds, 55°C for 30 seconds, 68°C for 40 seconds] and 10 minutes at 68°C. At the end of the PCR amplification, products were analyzed on agarose gels stained with ethidium bromide and visualized with UV light. PCR product was extracted from gel using QiaQuick™ gel extraction kit. The extracted DNA product (Figure 34) was sequenced by direct sequencing using the gene specific primers from above (Hy-Labs, Israel), resulting in the expected sequence of Troponin variant (Figure 35). It was concluded that the predicted Troponin variant is indeed a naturally expressed variant in a normal human tissue as shown in Figure 34.
2. Cloning of Troponin variant into bacterial expression vector 257 The Troponin splice variant coding sequence was prepared for cloning by PCR amplification using the fragment described above as template and Platinum Pfx DNA polymerase (Invitrogen Cat # 1 1708021) under the following conditions: 5? l - Amplification X 10 buffer (Invitrogen Cat # 1 1708021); 2μl - PCR product from above; lμl - dNTPs (lOmM each); l μl MgS04 (50mM) 5μl enhancer solution (Invitrogen Cat # 1 1708021); 33?μl - H20; lμl - of each primer (lOμM) and 1.25 units of Tag polymerase [Platinum Pfx DNA polymerase (Invitrogen Cat # 1 1708021)] in a total reaction volume of 50μl with a reaction program of 3 minutes at 94°C; 29 cycles of: [30 seconds at 94°C, 30 seconds at 58°C, 40 seconds at 68°C] and 7 minutes at 68 °C. The Primers listed below include specific sequences of the nucleotide sequence coπesponding to the splice variant and Nhel and Hindlll restriction sites.
Trop Nhelfor (SEQ ID NO: 359) - ACAGCTAGCATGGCGGATGGGAGCAGC
TropHindlllrev (SEQ ID NO: 360) - CCTAAGCTTCACCAATCCGAGCATGAC The PCR product was then double digested with Nhel and Hindlll (New England Biolabs (UK) LTD), and inserted into pRSET-A (Invitrogen, Cat# V351-20), previously digested with the same enzymes, in- frame to an N-terminal 6His-tag, to give HisTroponin T7 pRSET (Figure 36). The coding sequence encodes for a protein having the 6His-tag at the N' end (6His residues in a row at one end of the protein), and 8 additional amino acids encoded by the pRSET vector. The sequence of the Troponin insert in the final plasmid, as well as its flanking regions, were verified by sequencing and found to be identical to the desired sequences. The complete sequence of His Troponin T7 pRESTA is shown in Figure 37 (SEQ ID NO:386). Figure 38 shows the translated sequence of Troponin variant with the location of the His- tag marked (SEQ ID NO:387).
3. Bacterial cell growth and induction of protein expression HisTroponin pRSETA DNA was transformed into competent BL21Gold cells (Stratagene Cat#230134). Ampicillin resistant transformants were screened and positive clones were further analyzed by restriction enzyme digestion and sequence verification. 258 Cells containing the HisTroponin T7 pRSET vector or empty pRSET vector (as negative control) were grown in LB medium, supplemented with Ampicillin (50 μg/ml) and chlorarnphenicol (34 μg/ml). Cells were grown until O.D.βoonm reaches 0.5. This value was reached in about 3 hours. lmM IPTG (Roche, Cat #724815) was added and the cells were grown at 37°C for additional 3 hours. 1 ml of each culture was removed for gel analysis at To and T .
3.1. Coomassie staining and Western blotting Results The time course of small-scale expression of Troponin in BL21Gold is demonstrated in Figure 39a-b. The expression of a recombinant protein with the appropriate molecular weight (11 kDa) was detected both by Coomassie staining (Figure 39a) and by Western blot using anti His- antibodies (BD Clontech, Ref 631212) (Figure 39b). It was concluded that the protein encoded by Troponin variant T7 could be expressed in bacterial cells.
DESCRIPTION FOR CLUSTER HUMSMCK Cluster HUMSMCK features 5 transcript(s) and 14 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
Table 2 - Segments of interest w^ mm 259
Table 3 - Proteins of interest
These sequences are variants of the known protein Creatine kinase, sarcomeric mitochondrial precursor (SwissProt accession identifier KCRS HUMAN; known also according to the synonyms EC 2.7.3.2; S- MtCK; Mib-CK; Basic-type mitochondrial creatine kinase), refened to herein as the previously known protein. Protein Creatine kinase, sarcomeric mitochondrial precursor is known or believed to have the following function(s): Reversibly catalyzes the transfer of phosphate between ATP and 260 various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. The sequence for protein Creatine kinase, sarcomeric mitochondrial precursor is given at the end of the application, as "Creatine kinase, sarcomeric mitochondrial precursor amino acid sequence" (SEQ ID NO:388). Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein
Protein Creatine kinase, sarcomeric mitochondrial precursor localization is believed to be Mitochondrial inner membrane; outer side.
The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: energy pathways; muscle contraction, which are annotation(s) related to Biological Process; creatine kinase; transferase, transferring phosphorus -containing groups, which are annotation(s) related to Molecular Function; and mitochondrion, 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/>.
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster HUMSMCK. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the yaxis of Figure 23 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). 261 Overall, the following results were obtained as shown with regard to the histogram in Figure 23, concerning the number of heart-specific clones in libraries/sequences; as well as with regard to the histogram in Figure 24, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 18.1 ; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 2.4; and fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 3.60E-23. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle -specific ESTs which was found to be 18.1 , which clearly supports specific expression in heart tissue. As noted above, cluster HUMSMCK features 5 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Creatine kinase, sarcomeric mitochondrial precursor. A description of each variant protein according to the present invention is now provided. Variant protein HUMSMCK P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMSMCK_T5. An alignment is given to the known protein (Creatine kinase, sarcomeric mitochondrial 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 ofthe variant protein according to the present invention to each such aligned protein is as follows: 2 62 Comparison report between HUMSMCK_P4 and KCRS HUMAN Vl : l .An isolated chimeric polypeptide encoding for HUMSMCK_P4, comprising a first amino acid sequence being at least 90 % homologous to MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRK HNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYE VFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQFDEHYVLSSRVRTGRSIRGLSL PPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPL LTCAGMARDWPDARGIWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLK EVERLIQERGWEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSKILENLRLQ KRGTGGVDTAAVADVYD1SNIDRIGRSEV coπesponding to amino acids 1 - 381 of KCRS_HUMAN_V1 , which also coπesponds to amino acids 1 - 381 of HUMSMCK_P4, 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 TSLSLS conesponding to amino acids 382 - 387 of HUMSMCK_P4, 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 HUMSMCK_P4, 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 TSLSLS in HUMSMCKJM.
It should be noted that the known protein sequence (KCRS_HUMAN; SEQ ID NO:388) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for KCRS HUMAN Vl (SEQ ID NO:347). These changes were previously known to occur and are listed in the table below.
Table 5 - Changes to KCRS_HUMAN_V1
75 conflict 263
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 intracellular because of manual inspection of known protein localization and/or gene structure. Variant protein HUMSMCK_P4 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HUMSMCK_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations
Variant protein HUMSMCK P4 is encoded by the following transcript(s): HUMSMCK_T5, for which the sequence(s) s/are given at the end of the application. The coding portion of transcript HUMSMCK T5 is shown in bold; this coding portion starts at position 1305 and ends at position 2465. 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 HUMSMCK P4 sequence provides support for the deduced 264 sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs
Vaπant protein HUMSMCK P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMSMCK T6. An alignment is given to the known protein (Creatine kinase, sarcomeric mitochondrial 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 HUMSMCK P5 and KCRS_HUMAN_V 1 : l.An isolated chimeric polypeptide encoding for HUMSMCK P5, comprising a first amino acid sequence being at least 90 % homologous to MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRK HNNCMAECLTPAΓYAKLRNKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYE 265 VFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQFDEHYVLSSRVRTGRSIRGLSL PPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPL LTC AGMA RD WPD ARGI WHNY DKTFLI WINEEDHTRVISM EKGGNMKR VFERFCRGLK EVERLIQERGWEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLSK corresponding to amino acids 1 - 338 of KCRS_HUMAN_V1, which also conesponds to amino acids 1 - 338 of HUMSMCK_P5, 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 VLLCAQWP conesponding to amino acids 339 - 346 of HUMSMCK P5, 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 HUMSMCK_P5, comprising a polypeptide being at least 70%>, optionally at least about 80%o, preferably at least about 85%>, more preferably at least about 90% and most preferably at least about 95%> homologous to the sequence VLLCAQWP in HUMSMCK P5.
It should be noted that the known protein sequence (KCRS_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for KCRS HUMAN V 1. These changes were previously known to occur and are listed in the table below. Table 8 - Changes to KCRS_HUMAN_ VI
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 intracellular because of manual inspection of known protein localization and/or gene structure. 266 Variant protein HUMSMCK_P5 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acιd(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMSMCK_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations
Variant protein HUMSMCK P5 is encoded by the following transcript(s): HUMSMCK_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMSMCK T6 is shown in bold; this coding portion starts at position 1305 and ends at position 2342. 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 HUMSMCK P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs
267
Variant protein HUMSMCK P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMSMCK_T7 and HUMSMCK T11. An alignment is given to the known protein (Creatine kinase, sarcomeric mitochondrial 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 HUMSMCK P6 and KCRS_HUMAN_V1 : l.An isolated chimeric polypeptide encoding for HUMSMCK P6, comprising a first amino acid sequence being at least 90 % homologous to MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRK HNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYE VFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQFDEHYVLSSRVRTGRSIRGLSL PPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLID coπesponding to amino acids 1 - 223 of KCRS HUMAN Vl, which also coπesponds to amino acids 1 - 223 of HUMSMCK_P6, 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 A coπesponding to amino acids 224 - 224 of HUMSMCK P6, wherein said first amino acid sequence and second amino acid sequence are 268 contiguous and in a sequential order
It should be noted that the known protein sequence (KCRS HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for KCRS HUMAN V 1 These changes were previously known to occur and are listed in the table below. Table 11 - Changes to KCRS_HUMAN_V1
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 intracellular because of manual inspection of known protein localization and/or gene structure. Vanant protein HUMSMCK_P6 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HUMSMCK_P6 sequence provides support for the deduced sequence of this variant protein according b the present invention). Table 12 - Amino acid mutations
269
Variant protein HUMSMCK_P6 is encoded by the following transcript(s): HUMSMCK T7 and HUMSMCK T1 1, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMSMCK T7 is shown in bold; this coding portion starts at position 1305 and ends at position 1976. 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 HUMSMCK P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Nucleic acid SNPs
The coding portion of transcript HUMSMCK T11 is shown in bold; this coding portion 270 starts at position 1305 and ends at position 1976. 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 HUMSMCK_P6 sequence provides support for the deduced sequence of this vanant protein according to the present invention). Table 14 - Nucleic acid SNPs
Variant protein HUMSMCK_P8 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMSMCK_T9. An alignment is given to the known protein (Creatine kinase, sarcomeric mitochondrial 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 HUMSMCK P8 and KCRS_HUM AN V 1 : l .An isolated chimeric polypeptide encoding for HUMSMCK P8, comprising a first amino acid sequence being at least 90 %> homologous to MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRK HNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYE 271 VFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQFDEHYVLSSRVRTGRSIRGLSL PPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPL LTCAGMARDWPDARGIWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLK EV corresponding to amino acids 1 - 294 of KCRS HUM AN_V 1 , which also coπesponds to amino acids 1 - 294 of HUMSMCK P8, 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 RCYLRFLDIY coπesponding to amino acids 295 - 304 of HUMSMCK P8, 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 HUMSMCK P8, comprising a polypeptide being at least 70%, optionally at least about 80%o, preferably at least about 85%, more preferably at least about 90%> and most preferably at least about 95% homologous to the sequence RCYLRFLDIY in HUMSMCK P8.
It should be noted that the known protein sequence (KCRS_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for KCRS HUMAN Vl. These changes were previously known to occur and are listed in the table below. Table 15 - Changes to KCRS_HUMAN_V1
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 intracellular because of manual inspection of known protein localization and/or gene structure. 272 Variant protein HUMSMCK_P8 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HUMSMCK P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 16 - Amino acid mutations
Variant protein HUMSMCK P8 is encoded by the following transcript(s): HUMSMCK T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMSMCK T9 is shown in bold; this coding portion starts at position 1305 and ends at position 2216. 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 HUMSMCK P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 17 - Nucleic acid SNPs
273
As noted above, cluster HUMSMCK features 14 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 HUMSMCK_node_0 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): HUMSMCK_T5, HUMSMCK T6, HUMSMCK T7, HUMSMCK T9 and HUMSMCK T11. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts
27 4 Segment cluster HUMSMCK_node_7 according to the present invention is supported by 47 libraries The number of hbranes was determined as previously descnbed This segment can be found in the following transcπpt(s) HUMSMCK T5, HUMSMCK_T6, HUMSMCK T7, HUMSMCK T9 and HUMSMCK_T11 Table 19 below describes the starting and ending position of this segment on each transcript Table 19 - Segment location on transcripts
Segment cluster HUMSMCK_node_12 according to the present invention is supported by 54 hbranes The number of hbranes was detennined as previously descπbed This segment can be found in the following transcπpt(s) HUMSMCK 5, HUMSMCK T6, HUMSMCK T7, HUMSMCK T9 and HUMSMCK_T11 Table 20 below describes the starting and ending position of this segment on each transcnpt Table 20 - Segment location on transcripts
275
Segment cluster HUMSMCK_node_17 according to the present invention is supported by 48 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMSMCK_T5, HUMSMCK_T6, HUMSMCK T7, HUMSMCK T9 and HUMSMCK_T1 1. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
Segment cluster HUMSMCK_node_22 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): HUMSMCK T5, HUMSMCK T6, HUMSMCK T7, HUMSMCK T9 and HUMSMCK T11. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
27 6
Segment cluster HUMSMCK_node_23 according to the present invention is supported by 3 libraries The number of libraries was determined as previously descπbed This segment can be found in the following transcπpt(s) HUMSMCK T9 and HUMSMCK Tl 1 Table 23 below describes the starting and ending position of this segment on each transcript Table 23 - Segment location on transcripts
Segment cluster HUMSMCK_node_25 according to the present invention is supported by 58 hbranes The number of hbranes was detennined as previously descπbed This segment can be found in the following transcπpt(s) HUMSMCK_T5, HUMSMCK_T6 and HUMSMCK_T7. Table 24 below describes the starting and ending position of this segment on each transcπpt Table 24 - Segment location on transcripts
Segment cluster HUMSMCK_node_26 according to the present invention is supported by 1 hbranes The number of libraries was determined as previously described. This segment can be found in the following transcπpt(s) HUMSMCK_T6. Table 25 below descnbes the starting and endmg position of this segment on each transcπpt 277 Table 25 - Segment location on transcripts
Segment cluster HUMSMCK_node_28 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 transcnpt(s) HUMSMCK_T5 and HUMSMCK T7. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts
Segment cluster HUMSMCK_node_29 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): HUMSMCK_T5. Table 27 below describes the starting and ending position of this segment on each transcnpt. Table 27 - Segment location on transcripts
Segment cluster HUMSMCK_node_32 according to the present invention is supported by 62 hbraπes. The number of libraries was determined as previously descπbed. This segment can 278 be found in the following transcπpt(s) 1IUMSMCK_T7 Table 28 below describes the starting and ending position of this segment on each tianscnpt Table 28 - Segment location on transcripts
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 HUMSMCK node l 1 according to the present invention can be found in the following transcnpt(s) HUMSMCK T5, HUMSMCK_T6, HUMSMCK_T7, HUMSMCK T9 and HUMSMCK T1 1 Table 29 below descnbes the starting and ending position of this segment on each transcπpt Table 29 - Segment location on transcripts
Segment cluster HUMSMCK_node_14 according to the present invention is supported by 38 hbraπes The number of libraπes was determined as previously descπbed This segment can be found in the followmg transcπpt(s) HUMSMCK_T5, HUMSMCK_T6, HUMSMCK T7, HUMSMCK T9 and HUMSMCK_T11 Table 30 below descnbes the starting and ending 279 position of this segment on each transcript. Table 30 - Segment location on transcripts
Segment cluster HUMSMCK_node_19 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): HUMSMCK T5, HUMSMCK T6 and HUMSMCK_T9. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: KCRS_HUMAN_V1
Sequence documentation:
Alignment of: HUMSMCK_P4 x KCRS HUMAN /1 280
Alignment segment 1/1:
Quality: 3745.00 Escore: 0 Matching length: 381 Total length: 381 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment:
1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50 II I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I 1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50 . . . . . 51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100 I I I I I I I I I I I I I I I I I II I I I I II I I I I I II I I I I I I I I II I I I 1 I I I I 51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100 101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150 I I I I I I I I I I I I I I I I I I I I I II I II I I I I I I I I I I I I I I I I I I I I I I I I 101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150
151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200 I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200
201 GDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPLLTCAGMARDWPDARG 250 I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I 201 GDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPLLTCAGMARDWPDARG 250
251 I HNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQE 300 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 251 I HNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQE 300
301 RG EFM NERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSKILENLR 350 I I II I I I I II I II I I I I I I I I I I II I I I I I II I I I I I I I I I I I I I I I I I I 301 RGWEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSKILENLR 350 281 351 LQKRGTGGVDTAAVADVYDISNIDRIGRSEV 381 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 351 LQKRGTGGVDTAAVADVYDISNIDRIGRSEV 381
Sequence name: KCRS_HUMAN_V1
Sequence documentation:
Alignment of: HUMSMCK_P5 x KCRS_HUMAN_V1
Alignment segment 1/1:
Quality: 3344.00 Escore: 0 Matching length: 338 Total length: 338 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment:
1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50
51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I 51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100 101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150
151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200 I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200
201 GDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPLLTCAGMARDWPDARG 250 282 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 201 GDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPLLTCAGMARDWPDARG 250
251 IWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQE 300 I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 II I I I I II I I I I I I I I I I I I I 251 IWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQE 300
301 RGWEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLSK 338 I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I 301 RGWEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLΞK 338
Sequence name: KCRS_HUMAN_V1
Sequence documentation:
Alignment of: HUMSMCK_P6 x KCRS_HUMAN_V1
Alignment segment 1/1: Quality: 2176.00 Escore: 0 Matching length: 223 Total length: 223 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50
51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I 51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100
101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150 283 151 TQGQFDEHYVLSSRVRTGRS IRGLSLPPACTRAERREVENVAITALEGLK 200 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200
201 GDLAGRYYKLSEMTEQDQQRLID 223 II I I I I I I I I I I I I I I I I I I I I I 201 GDLAGRYYKLSEMTEQDQQRLID 223
Sequence name: KCRS_HUMAN_V1
Sequence documentation:
Alignment of: HUMSMCK_P8 x KCRS_HUMAN_V1
Alignment segment 1/1:
Quality: 2904.00 Escore: 0 Matching length: 294 Total length: 294 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPP 50 51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 SADYPDLRKHNNCMAECLTPAIYAKLRNKVTPNGYTLDQCIQTGVDNPGH 100
101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150 I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I II 101 PFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKI 150
151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200 284 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 TQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLK 200
201 GDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPLLTCAGMARDWPDARG 250 I II I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 201 GDLAGRYYKLSEMTEQDQQRLIDDHFLFDKPVSPLLTCAGMARD PDARG 250
251 IWHNYDKTFLI INEEDHTRVISMEKGGNMKRVFERFCRGLKEV 294 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 251 I HNYDKTFLI INEEDHTRVI SMEKGGNMKRVFERFCRGLKEV 2 94
DESCRIPTION FOR CLUSTER H88495 Cluster H88495 features 7 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
Table 2 - Segments of interest
285
These sequences are variants of the known protein Sarcoplasmic reticulum histidine-rich calcium-binding protein precursor (SwissProt accession identifier SRCH_HUMAN), refeπed to 286 herein as the previously known protein Protein Sarcoplasmic reticulum histidine-nch calcium-binding protein precursor is known or believed to have the following functιon(s) May play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle The sequence for protein Sarcoplasmic reticulum histidine-nch calcium-binding protein precursor is given at the end of the application, as "Sarcoplasmic reticulum histidine-nch calcium-binding protein precursor amino acid sequence" (SEQ ID NO 389). Known polymoφhisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein
Protein Sarcoplasmic reticulum histidine-rich calcium-binding protein precursor localization is believed to be Sarcoplasmic reticulum lumen. The following GO Annotatιon(s) apply to the previously known protein. The following annotation(s) were found: muscle contraction, which are annotatιon(s) related to Biological Process; and calcium binding, which are annotatιon(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/>.
The heart- selective diagnostic marker prediction engine provided the followmg results with regard to cluster H88495. Predictions were made for selective expression of transcnpts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 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 m that 287 category, according to parts per million). Overall, the following results were obtained as shown with regard to the histogram in Figure 25, concerning the number of heart-specific clones in libraries/sequences; as well as with regard to the histogram in Figure 26, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 13.7; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 2.3; and fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 1.90E-06. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 13.7, which clearly supports specific expression in heart tissue. As noted above, cluster H88495 features 7 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Sarcoplasmic reticulum histidine-rich calcium-binding protein precursor. A description of each variant protein according to the present invention is now provided. Variant protein H88495 PEA 3 P15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H88495_PEA_3_T3, H88495_PEA_3_T4 and H88495_PEA_3_T7. An alignment is given to the known protein (Sarcoplasmic reticulum histidine-rich calcium-binding protein 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: 28 8
Comparison report between H88495 PEA 3JM 5 and SRCH_HUMAN_V1 : l .An isolated chimeric polypeptide encoding for H88495_PEA_3_P15, comprising a first amino acid sequence being at least 90 % homologous to MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNN corresponding to amino acids 1 - 42 of SRCH_HUMAN_V1, which also coπesponds to amino acids 1 - 42 of H88495_PEA_3_P15, a bridging amino acid N conesponding to amino acid 43 of H88495_PEA_3_P15, a second amino acid sequence being at least 90 % homologous to TGVAGLSEEASAELRHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPSHRS HSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHR HRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAH RHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDDDVSTEYGHQAHRHQDHRKEE VEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHR QSHQDEETGHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEERREERAEVG APLSPDHSEEEEEEEEGLEEDEPRFΗIPNPLDRREEAGGASSEEESGEDTGPQDAQEYGN YQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQ conesponding to amino acids 44 - 657 of SRCH_HUMAN_V1, which also coπesponds to amino acids 44 - 657 of H88495 PEA 3 P15, 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
VRPHLTLKAPLGLRMHRDPLRTPSPKSWPLTQPLTPDATLTPQAILTPTLT coπesponding to amino acids 658 - 708 of H88495_PEA_3_P15, 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 H88495 PEA 3 P15, 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 VRPHLTLKAPLGLRMHRDPLRTPSPKSWPLTQPLTPDATLTPQAILTPTLT in 289 H88495 PEA 3 PI 5.
It should be noted that the known protein sequence (SRCH HUMAN; SEQ ID NO:389) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for SRCH HUMAN V1 (SEQ ID NO:346). These changes were previously known to occur and are listed in the table below. Table 5 - Changes to SRCH_HUMAN_V1
The location of the variant protein was detennined 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 H88495 PEA 3 P15 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 H88495_PEA_3_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations
2 90
Vanant protein H88495_PEA_3_P15 is encoded by the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4 and H88495_PEA_3_T7, for which the ssquence(s) is/are given at the end of the application. The coding portion of transcript H88495_PEA_3_T3 is shown in bold; this coding portion starts at position 743 and ends at position 2866. 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 H88495_PEA_3_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention).
Table 7 - Nucleic acid SNPs
291
The coding portion of transcript H88495_PEA_3_T4 is shown in bold; this coding portion starts at position 743 and ends at position 2866. 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 H88495_PEA_3_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs
2 92
The coding portion of transcript H88495_PEA_3_T7 is shown in bold; this coding portion starts at position 743 and ends at position 2866. 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 H88495_PEA_3_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs
293
Variant protein H88495_PEA_3_P 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) H88495_PEA_3_T5 and H88495_PEA_3_T6. An alignment is given to the known protein (Sarcoplasmic reticulum histidine-rich calcium-binding protein 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 H88495 PEA 3 P16 and SRCH HUMAN V1 : l .An isolated chimeric polypeptide encoding for H88495_PEA_3_P16, comprising a first amino acid sequence being at least 90 % homologous to MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNN coπesponding to amino acids 1 - 42 of SRCH_HUMAN_V1, which also coπesponds to amino acids 1 - 42 of H88495 PEA 3 P16, a bridging amino acid N coπesponding to amino acid 43 of H88495 PEA 3 P16, a second amino acid sequence being at least 90 % homologous to TGVAGLSEEASAELRHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPSHRS HSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEAS TEYGHQAHR HRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAH RHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDDDVSTEYGHQAHRHQDHRKEE VEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHR QSHQDEETGHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEERREERAEVG APLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQEYGN YQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQHCQFCYLCPLVCETVCAPG coπesponding to amino acids 44 - 676 of SRCH_HUMAN_V1, which also coπesponds to 294 amino acids 44 - 676 of H88495_PEA_3_P16, 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 EHGRGPGKT coπesponding to amino acids 677 - 685 of H88495_PEA_3_P16, 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 H88495 PEA 3 P16, comprising a polypeptide being at least 70%o, 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 EHGRGPGKT in H88495_PEA_3_P16.
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 it is a partial protein, because both trans-membrane region prediction programs predict that this protein has a trans- membrane region. Variant protein H88495_PEA_3_P16 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 H88495 PEA 3 P16 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations
295
Variant protein H88495_PEA_3_P16 is encoded by the following transcript(s): H88495_PEA_3_T5 and H88495JPEA 3 T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H88495_PEA_3_T5 is shown in bold; this coding portion starts at position 743 and ends at position 2797. 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 H88495 PEA 3 P16 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs
296
The coding portion of transcript H88495_PEA_3_T6 is shown in bold; this coding portion starts at position 743 and ends at position 2797. 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 H88495_PEA_3_P16 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Nucleic acid SNPs
297
Variant protein H88495_PEA_3_P17 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H88495_PEA_3_T8. An alignment is given to the known protein (Sarcoplasmic reticulum histidine-rich calcium-binding protein 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 H88495JPEA 3 P17 and SRCH HUMAN V1 : l.An isolated chimeric polypeptide encoding for H88495_PEA_3_P17, comprising a first amino acid sequence being at least 90 % homologous to MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNN coπesponding to amino acids 1 - 42 of SRCH HUMAN Vl, which also coπesponds to amino acids 1 - 42 of H88495_PEA_3_P17, a bridging amino acid N coπesponding to amino acid 43 of H88495_PEA_3_P17, a second amino acid sequence being at least 90 % homologous to TGVAGLSEEASAELRHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPSHRS HSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHR HRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAH RHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDDDVSTEYGHQAHRHQDHRKEE VEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHR QSHQDEETGHGQRGSIKEMSHHPPGHTWKDRSHLRKDDSEEEKEKEEDPGSHEEDDE SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEERREERAEVG APLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQEYGN 298
YQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQ corresponding to amino acids 44 -
657 of SRCH_HUMAN_V 1 , which also corresponds to amino acids 44 - 657 of H88495_PEA_3_P17, and a third amino acid sequence being at least 70%, optionally at least 80%o, preferably at least 85%>, more preferably at least 90% and most preferably at least 95%> homologous to a polypeptide having the sequence
GPGRHAGNAGTLTQSLDCDAGVPPPAFQPLSTSYIYFSE corresponding to amino acids
658 - 696 of H88495_PEA_3_P17, 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 H88495_PEA_3_P17, comprising a polypeptide being at least 70%>, optionally at least about 80%, preferably at least about 85%o, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GPGRHAGNAGTLTQSLDCDAGVPPPAFQPLSTSYIYFSE in
H88495_PEA_3_P17.
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 H88495 PEA 3 P17 also has the following non-silent SNPs (Single
Nucleotide Polymoφhisms) 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 H88495_PEA_3_P17 sequence provides support for the deduced sequence of this variant protein according to the present invention).
Table 15 - Amino acid mutations 299
Variant protein H88495 PEA 3 P17 is encoded by the following transcript(s): H88495 PEA 3 T8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H88495_PEA_3_T8 is shown in bold; this coding portion starts at position 743 and ends at position 2830. 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 H88495_PEA_3_P17 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 16 - Nucleic acid SNPs
300
Variant protein H88495_PEA_3_P18 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H88495_PEA_3_T9. An alignment is given to the known protein (Sarcoplasmic reticulum histidine-rich calcium-binding protein 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 H88495_PEA_3_P18 and SRCH HUMAN Vl : l.An isolated chimeric polypeptide encoding for H88495 PEA 3 P18, comprising a first amino acid sequence being at least 90 %> homologous to MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNN coπesponding to amino acids 1 - 42 of SRCH_HUMAN_V1, which also coπesponds to amino acids 1 - 42 of H88495_PEA_3_P18, a bridging amino acid N coπesponding to amino acid 43 of H88495 PEA 3 P18, a second amino acid sequence being at least 90 % homologous to TGVAGLSEEASAELRHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPSHRS HSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHR HRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAH RHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDDDVSTEYGHQAHRHQDHRKEE 301 VEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHR QSHQDEETGHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEERREERAEVG APLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDT coπesponding to amino acids 44 - 610 of SRCH HUMAN V1, which also coπesponds to amino acids 44 - 610 of H88495_PEA_3_P18, 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 AMH coπesponding to amino acids 611 - 613 of H88495_PEA_3_P18, 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.
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 H88495_PEA_3_P18 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 H88495 PEA 3 P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 18 - Amino acid mutations
302
Variant protein H88495 PEA 3 P18 is encoded by the following transcript(s): H88495_PEA_3_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H88495_PEA_3_T9 is shown in bold; this coding portion starts at position 743 and ends at position 2581. 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 H88495_PEA_3_P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 19 - Nucleic acid SNPs
303
As noted above, cluster H88495 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 H88495_PEA_3_node_0 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_l according to the present invention is supported 304 by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495JPEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_4 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
305
Segment cluster H88495_PEA_3_node_9 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_13 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9. Table 24 below describes the starting and ending position of this segment on each transcript. 306 Table 24 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_19 according to the present invention is supported by 4 libraπes. The number of libraries was determined as previously descnbed. This segment can be found in the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4 and H88495_PEA_3_T7. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_21 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): H88495_PEA_3_T5, H88495_PEA_3_T6 and H88495 PEA 3 T7. Table 26 below describes the starting and ending position of this segment on each transcript. 307 Table 26 - Segment location on transcripts Transpripf name ^ Segment •* Segment , z"*" f starting^position endin position H88495 PEA 3 T5 2769 3095 H88495 PEA 3 T6 2769 3095 H88495 PEA 3 T7 3020 3346
Segment cluster H88495_PEA_3_node_26 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 27 below describes the starting and ending position of this segment on each transcπpt. Table 27 - Segment location on transcripts
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. 308 Segment cluster H88495_PEA_3_node_2 according to the present invention is supported by 14 hbranes The number of libraπes was determined as previously described This segment can be found in the following transcπpt(s) H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9 Table 28 below describes the starting and ending position of this segment on each transcript Table 28 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_5 according to the present invention is supported by 16 hbranes The number of hbraπes was detennined as previously described. This segment can be found in the following transcnpt(s) H88495_PEA_3_T3, H88495 PEA 3 T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9. Table 29 below describes the starting and ending position of this segment on each transcnpt. Table 29 - Segment location on transcripts
309
Segment cluster H88495_PEA_3_node_6 according to the present invention is supported by 14 libraries. The number of libranes was detennined as previously described. This segment can be found in the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_7 according to the present invention can be found in the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts 310
Segment cluster H88495_PEA_3_node_8 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 transcnpt(s) H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9 Table 32 below describes the starting and endmg position of this segment on each transcπpt Table 32 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_10 according to the present invention can be 31 1 found in the following transcπpt(s) H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 33 below describes the starting and ending position of this segment on each transcript Table 33 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_l 1 according to the present invention can be found in the following transcπpt(s)- H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9. Table 34 below descnbes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts
312
Segment cluster H88495_PEA_3_node_12 according to the present invention can be found in the following transcript(s). H88495 PEA 3 T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495 PEA 3 T9 Table 35 below describes the starting and ending position of this segment on each transcπpt. Table 35 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_14 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously descπbed. This segment can be found in the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and H88495_PEA_3_T9. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts 313
Segment cluster H88495_PEA_3_node_16 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7 and H88495_PEA_3_T8. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_18 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): H88495_PEA_3_T3, H88495_PEA_3_T4, 314 H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7, H88495_PEA_3_T8 and II88495_PEA_3_T9 Table 38 below describes the starting and ending position of this segment on each transcript Table 38 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_20 according to the present invention is supported by 27 hbranes The number of hbranes was detennined as previously described This segment can be found in the following transcπpt(s) H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7 and H88495_PEA_3_T9 Table 39 below describes the starting and ending position of this segment on each transcπpt.
315
Segment cluster H88495_PEA_3_node_23 according to the present invention can be found in the following transcript(s): H88495_PEA_3_T3, H88495_PEA_3_T4 and H88495_PEA_3_T9. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts
Segment cluster H88495_PEA_3_node_24 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): H88495_PEA_3_T3, H88495_PEA_3_T4, H88495_PEA_3_T5, H88495_PEA_3_T6, H88495_PEA_3_T7 and H88495_PEA_3_T9. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts
316
Variant protein alignment to the previously known protein:
Sequence name: SRCH_HUMAN_V1
Sequence documentation:
Alignment of: H88495_PEA_3_P15 x SRCH_HUMAN_V1
Alignment segment 1/1: Quality: 6726.00 Escore: 0 Matching length: 657 Total length: 657 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.85 Total Percent Similarity: 100.00 Total Percent Identity: 99.85 Gaps: 0
Alignment :
1 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLS 50 II I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I : I II I I I I 1 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAGLS 50
51 EEASAE RHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG 100 I I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I II I 51 EEASAELRHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG 100 . . . . . 101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I II I I II I I I II I I I I I I II 101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150 151 HLPSHRSHSHQDEDEDEWSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200 I II I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I 151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200
201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250 I I I II I I I II I I I I I I I I I I I I I I I I I I I I II I I I I M I I II I I I I I M I 201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250
251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300 317 I I I I I I I I I I I I I M I M I I II I I I I I I II II I I II I I I I I I I I I I I I II 251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300
301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350
351 EEEDEDVSTER HQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400 II I I I I I I I I I I I I I II I I II I I I I II I I 1 II I I I II I II I I I I I I I II I 351 EEEDEDVSTERWHQGPQHVHHG VDEEEEEEEITVQFGHYVASHQPRGHK 400
401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450 I I I II I I I II I II I I I I I I I I I I I I I I I I I I I I II II II I I II I I I II I I 401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450 . . . . . 451 GHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500 I I I II I I I I I I I I I I I I I I I I I I I II I I II I I I I I I I I I I I I I I I I I I II 451 GHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500 501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550 I I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I II I I I I I II 501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550
551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II 551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600
601 SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMG 650 I I I I I I I I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I 601 SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMG 650
651 EHCDQCQ 657 I I I I I I I 651 EHCDQCQ 657
Sequence name: SRCH_HUMAN_V1
Sequence documentation: 318
Alignment of: H88495_PEA_3_P16 x SRCH_HUMAN_V1
Alignment segment 1/1:
Quality: 6935.00 Escore: 0 Matching length: 676 Total length: 676 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.85 Total Percent Similarity: 100.00 Total Percent Identity: 99.85 Gaps: 0
Alignment :
1 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAG S 50 I I I I I I I I I I I I I I I I I I I I I I I M I I I I II I I I I I I I I I I I : I I I I I I I 1 MGHHRPWLHASVL AGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAG S 50
51 EEASAELRHH HSPRDHPDENKDVSTENGHHF SHPDREKEDEDVAKEYG 100 I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I II I I I I I II I I I I I I I I I I 51 EEASAELRHHLHSPRDHPDENKDVSTENGHHFWSHPDREKEDEDVAKEYG 100
101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150 I I I I I I I I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150 . . . . . 151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200 I I I I I I I I I I I I I II I I I I I I I I I I I I I II I I I I I I I I I I I I I II I I I I I 151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200 201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250
251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300 II I I I I I I I I I I I I I I I I I II I M I I I I I I I I I I I I I I I I I I I I I I I I I I 251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300
301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350 319 II II II II I I I I I I I I I II I II I I I I I II I I I I I I I I I I I I I I I I II I II 301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350
351 EEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400 I || I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I 351 EEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400
401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450 I I I I I I I I I I I I II I I I II I II I I I I I I I I I I I I I I I I I I I I I I II I II I 401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450
451 GHGQRGSIKEMSHHPPGHTWKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I 451 GHGQRGSIKEMSHHPPGHTWKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500 . . . . . 501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550 I I I I I I II I I I II I I II I I I I I I I I I I I I I I I I I I II I II I I I I II I I I I 501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550 551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600 I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I II I I I I I I I I I I II I I I I 551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600
601 SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMG 650 I I I II I I I I I I I I I I I I I I M I I I I I I I I II I I I I I I I I I I I I I I I I I I I 601 SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMG 650
651 EHCDQCQHCQFCYLCP VCETVCAPG 676 I I I I I I I I I II I I I I I I I I I I I II I I 651 EHCDQCQHCQFCYLCPLVCETVCAPG 676
Sequence name: SRCH_HUMAN_V1
Sequence documentation:
Alignment of: H88495_PEA_3_P17 x SRCH_HUMAN_V1
Alignment segment 1/1: 320
Quality: 6726.00 Escore 0 Matching length: 657 Total length 657 Matching Percent Similarity: 100.00 Matching Percent Identity 99.85 Total Percent Similarity: 100.00 Total Percent Identity 99.85 Gaps: 0
Alignment :
1 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLS 50 I I I I II I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I : I I I I I I I 1 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAGLS 50
51 EEASAELRHHLHSPRDHPDENKDVSTENGHHF SHPDREKEDEDVAKEYG 100 II I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 EEASAELRHHLHSPRDHPDENKDVSTENGHHF SHPDREKEDEDVAKEYG 100
101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150 I II I I I I I I I I I I I I II I I I I I I I I I II I I I I I II I I I I I I I I I I I I II I 101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150
151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200 I I I I I I I I I I I I I I I I I I I II II I I I I I I I I I II I I I I I I I I I I I II I I I 151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200
201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250 I I I I I I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I 201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250
251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300
301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I II I I I I I I II I I I I I I I I 301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350
351 EEEDEDVSTER HQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400 321 I II I II I I II I I I I I I I I I I I I I I I I I II I I II I I I I I I I I II II I II II 351 EEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400
401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450 I I I I I I I I I I I I I I I I I I I II I I II II I II II I I I I II I II I II I I I I I I 401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450
451 GHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I II I I I I II I 451 GHGQRGSIKEMSHHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500
501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550 I I I I I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I II I I I 501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550 . . . . . 551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600 I I I I I I I I I I I I I I I I I I I I I I I I I II II I I I I I I I I I II I I I I I I I I I I 551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600 601 SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMG 650 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II II I I I I I I II I I I I I II 601 SSEEESGEDTGPQDAQEYGNYQPGSLCGYCSFCNRCTECESCHCDEENMG 650
651 EHCDQCQ 657 1 I ! I I I I 651 EHCDQCQ 657
Sequence name: SRCH_HUMAN_V1
Sequence documentation:
Alignment of: H88495_PEA_3_P18 x SRCH_HUMAN_V1
Alignment segment 1/1:
Quality: 6206.00 Escore: 0 Matching length: 610 Total length: 610 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.84 322 Total Percent Similarity: 100.00 Total Percent Identity: 99.84 Gaps : 0
Alignment : . . . . . 1 MGHHRPWLHASVL AGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLS 50 I I II I I II I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I : I I I I I II 1 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAGLS 50 51 EEASAELRHHLHSPRDHPDENKDVSTENGHHF SHPDREKEDEDVAKEYG 100 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I II I I I I I I I I 51 EEASAELRHHLHSPRDHPDENKDVSTENGHHF SHPDREKEDEDVAKEYG 100
101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150 II I I I I I I I I II I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I II I I 101 HLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRH 150
151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I 151 HLPSHRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEE 200
201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I 201 EEEEASTEYGHQAHRHRGHGSEEDEDVSDGHHHHGPSHRHQGHEEDDDDD 250 . . . . . 251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRΞH 300 I I I I I I I I I I I I I I I I I II I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I 251 DDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSH 300 301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350 I I I I I I I I I I I I I I I I II I I I I I I I I I I II I I I I I I I I I II I I I I I I I I I 301 EEDDNDDDDVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRD 350
351 EEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400 I II I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II 351 EEEDEDVSTER HQGPQHVHHGLVDEEEEEEEITVQFGHYVASHQPRGHK 400
401 SDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 450 323 I I I I I I M I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I l l I 401 S DEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEET 4 50
4 51 GHGQRGS IKEMSHHPPGHTWKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500 I M I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I l l I 451 GHGQRGSIKEMSHHPPGHTWKDRSHLRKDDSEEEKEKEEDPGSHEEDDE 500
501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550 M I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 501 SSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEEDKEEEEEEEDEE 550
551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTI I PNPLDRREEAGGA 600 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 551 RREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGA 600
601 SSEEESGEDT 610 I II I I I I I I I 601 SSEEESGEDT 610
DESCRIPTION FOR CLUSTER Z36249 Cluster Z36249 features 4 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
Table 2 - Segments of interest 32 '
Table 3 - Proteins of interest
The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster Z36249. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 27 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 histogram in Figure 27, concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figure 28, concerning the actual expression of oligonucleotides in various tissues, including heart. 325 This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 33.8; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 27.8; and fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 1.60E-47.
One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 33.8, which clearly supports specific expression in heart tissue
As noted above, cluster Z36249 features 4 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 Z36249_PEA_3_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z36249 PEA 3 T2. 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 Z36249_PEA_3_P2 and Q96LE7 (SEQ ID NO:344): l.An isolated chimeric polypeptide encoding for Z36249 PEA 3 P2, comprising a first amino acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQREAELKJG KLEQRSKLENLEDLEIIIQLKKPvKKYRKTKVPVVKEPEPEII coπesponding to amino acids 1 - 115 of Q96LE7, which also coπesponds to amino acids 1 - 115 326 of Z36249_PEA_3_P2, and a second amino acid sequence being at least 90 % homologous to YKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLDVLKLLLNKG AKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDREGDTPLHDAVRLNRYK MIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTKAIFDSLRENSYKTSRIATF coπesponding to amino acids 152 - 319 of Q96LE7, which also coπesponds to amino acids 1 16 - 283 of Z36249_PEA_3_P2, 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 Z36249_PEA_3_P2, 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 IY, having a structure as follows: a sequence starting from any of amino acid numbers 1 15-x to 115; and ending at any of amino acid numbers 116+ ((n-2) - x), in which x varies from 0 to n-2.
Comparison report between Z36249_PEA_3_P2 and Q15327 (SEQ ID NO:345): l.An isolated chimeric polypeptide encoding for Z36249 PEA 3 P2, comprising a first amino acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQREAEL coπesponding to amino acids 1 - 70 of Q15327, which also coπesponds to amino acids 1 - 70 of Z36249 PEA 3 P2, a bridging amino acid K coπesponding to amino acid 71 of Z36249 PEA 3 P2, a second amino acid sequence being at least 90 % homologous to KKKLEQRSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEII coπesponding to amino acids 72 - 115 of Q15327, which also conesponds to amino acids 72 - 115 of Z36249 PEA 3 P2, and a third amino acid sequence being at least 90 % homologous to YKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLDVLKLLLNKG AKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDREGDTPLHDAVRLNRYK MIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTKAIFDSLRENSYKTSRIATF conesponding to amino acids 152 - 319 of Q15327, which also coπesponds to amino acids 116 - 283 of Z36249 PEA 3 P2, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 327 order. 2.An isolated chimeric polypeptide encoding for an edge portion of Z36249_PEA_3_P2, 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 IY, having a structure as follows: a sequence starting from any of amino acid numbers 1 15-x to 1 15; and ending at any of amino acid numbers 1 16+ ((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: 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 Z36249 PEA 3 P2 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 Z36249_PEA_3_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 4 - Amino acid mutations
Variant protein Z36249 PEA 3 P2 is encoded by the following transcript(s): Z36249 PEA 3 T2, for which the sequence(s) is/are given at the end of the application. The 328 coding portion of transcript Z36249_PEA_3_T2 is shown in bold; this coding portion starts at position 250 and ends at position 1098. 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 Z36249 PEA 3 P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Nucleic acid SNPs
Variant protein Z36249 PEA 3 P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z36249_PEA_3_T3. 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: 329
Comparison report between Z36249_PEA_3_P3 and Q96LE7: l .An isolated chimeric polypeptide encoding for Z36249_PEA_3_P3, comprising a first amino acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEUTE PVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDEYKRTALHRACLEGHLAIVEKLMEA GAQIEFRDM conesponding to amino acids 1 - 184 of Q96LE7, which also corresponds to amino acids 1 - 184 of Z36249_PEA_3_P3, 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 VNIFLCLGMSQKK coπesponding to amino acids 185 - 197 of Z36249 PEA 3 P3, 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 Z36249_PEA_3_P3, 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 VNIFLCLGMSQKK in Z36249_PEA_3_P3.
Comparison report between Z36249_PEA_3_P3 and Q 15327: l.An isolated chimeric polypeptide encoding for Z36249 PEA 3 P3, comprising a first amino acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQREAEL coπesponding to amino acids 1 - 70 of QI 5327, which also coπesponds to amino acids 1 - 70 of Z36249 PEA 3 P3, a bridging amino acid K coπesponding to amino acid 71 of Z36249_PEA_3_P3, a second amino acid sequence being at least 90 % homologous to
KKKLEQRSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENK LPVVEKFLSDKNNPDVCDEYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDM coπesponding to amino acids 72 - 184 of Q 15327, which also coπesponds to amino acids 72 - 184 of Z36249 PEA 3 P3, 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 330 95% homologous to a polypeptide having the sequence VNIFLCLGMSQKK coπesponding to amino acids 185 - 197 of Z36249_PEA_3_P3, 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 Z36249_PEA_3_P3, 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 VNIFLCLGMSQKK in Z36249_PEA_3_P3. 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 Z36249 PEA 3 P3 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 Z36249_PEA_3_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations
Variant protein Z36249 PEA 3 P3 is encoded by the following transcript(s): 331 Z36249_PEA_3_T3, for which the sequence(s) is/are given at the end of the application The coding portion of transcript Z36249_PEA_3_T3 is shown in bold, this coding portion starts at position 250 and ends at position 840 The transcnpt 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 Z36249_PEA_3_P3 sequence provides support for the deduced sequence of this vanant protein according to the present invention). Table 7 - Nucleic acid SNPs
Variant protein Z36249 PEA 3 P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z36249_PEA_3_T5. 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 Z36249_PEA_3_P4 and Q96LE7: l.An isolated chimeric polypeptide encoding for Z36249 PEA 3 P4, comprising a first ammo acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQPvEAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITE PVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDE coπesponding to amino acids 1 - 151 of Q96LE7, which also coπesponds to amino acids 1 - 151 of Z36249_PEA_3_P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 332 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRLMQSTAKSSSLILCFLCFTPVLLI corresponding to amino acids 152 - 177 of Z36249_PEA_3_P4, 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 Z36249_PEA_3_P4, 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 VRLMQSTAKSSSLILCFLCFTPVLLI in Z36249_PEA_3_P4. Comparison report between Z36249_PEA_3_P4 and Q15327: l .An isolated chimeric polypeptide encoding for Z36249 PEA 3 P4, comprising a first amino acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQREAEL coπesponding to amino acids 1 - 70 of QI 5327, which also conesponds to amino acids 1 - 70 of Z36249 PEA 3 P4, a bridging amino acid K conesponding to amino acid 71 of Z36249 PEA 3 P4, a second amino acid sequence being at least 90 % homologous to
KKKLEQRSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENK LPWEKFLSDKNNPDVCDE coπesponding to amino acids 72 - 151 of Q 15327, which also coπesponds to amino acids 72 - 151 of Z36249_PEA_3_P4, 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 VRLMQSTAKSSSLILCFLCFTPVLLI conesponding to amino acids 152 - 177 of Z36249 PEA 3 P4, 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 Z36249 PEA 3 P4, 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 VRLMQSTAKSSSLILCFLCFTPVLLI in Z36249_PEA_3_P4.
The location of the variant protein was determined according to results from a number of 333 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 only one of the two trans- membrane region prediction programs (Tmpred: 1 , Tmhmm: 0) has predicted that this protein has a trans -membrane region. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.
Variant protein Z36249_PEA_3_P4 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 Z36249 PEA 3 P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations
Variant protein Z36249 PEA 3 P4 is encoded by the following transcript(s): Z36249 PEA 3 T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z36249 PEA 3 T5 is shown in bold; this coding portion starts at position 250 and ends at position 780. The transcript also has the Mowing 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 Z36249_PEA_3_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs 334
Variant protein Z36249_PEA_3_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z36249_PEA_3_T9. 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 Z36249_PEA_3_P5 and Q96LE7: l .An isolated chimeric polypeptide encoding for Z36249 PEA 3 P5, comprising a first amino acid sequence being at least 90 % homologous to MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGE QQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKXRKKYRKTKVPVVKEPEPEIITE PVDVPTFLKAALENKLPWEKFLSDKNNPDVCDE coπesponding to amino acids 1 - 151 of Q96LE7, which also coπesponds to amino acids 1 - 151 of Z36249 PEA 3 P5, and a second amino acid sequence being at least 90 % homologous to LESTAIHWASRGGNLDVLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACE ADLNAKDREGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNG TKA.iFDSLRENSYKTSRlA.TF coπesponding to amino acids 185 - 319 of Q96LE7, which also coπesponds to amino acids 152 - 286 of Z36249 PEA 3 P5, 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 Z36249 PEA 3JP5, 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 335 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 EL, having a structure as follows: a sequence starting from any of amino acid numbers 151-x to 151 ; and ending at any of amino acid numbers 152+ ((n-2) - x), in which x varies from 0 to n-2.
Comparison report between Z36249_PEA_3_P5 and Q15327: l .An isolated chimeric polypeptide encoding for Z36249 PEA 3 P5, comprising a first amino acid sequence being at least 90 % homologous to MM VLK V EELVTGKKNGNGEAGEFLPEDFRDGE Y E AA VTLEKQEDLKTLL AHP VTLGE QQWKSEKQREAEL coπesponding to amino acids 1 - 70 of QI 5327, which also coπesponds to amino acids 1 - 70 of Z36249 PEA 3 P5, a bridging amino acid K conesponding to amino acid 71 of Z36249 PEA 3 P5, a second amino acid sequence being at least 90 % homologous to
KKKLEQRSKLENLEDLEΠIQLKXRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENK LPVVEKFLSDKNNPDVCDE coπesponding to amino acids 72 - 151 of Q 15327, which also coπesponds to amino acids 72 - 151 of Z36249 PEA 3 P5, and a third amino acid sequence being at least 90 % homologous to
LESTAIHWASRGGNLDVLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACE ADLNAKDREGDTPLHDAVRLNRYKMIRLLΓMYGADLNIKNCAGKTPMDLVLHWQNG TKAIFDSLRENSYKTSRIATF coπesponding to amino acids 185 - 319 of QI 5327, which also coπesponds to amino acids 152 - 286 of Z36249 PEA 3 P5, 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 chimeric polypeptide encoding for an edge portion of Z36249_PEA_3_P5, 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 EL, having a structure as follows: a sequence starting from any of amino acid numbers 151-x to 151; and ending at any of amino acid numbers 152+ ((n-2) - x), in which x varies from 0 to n-2. 336 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 Z36249_PEA_3_P5 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 Z36249 PEA 3 P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Amino acid mutations
Variant protein Z36249 PEA 3 P5 is encoded by the following transcript(s): Z36249_PEA_3_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z36249_PEA_3_T9 is shown in bold; this coding portion starts at position 250 and ends at position 1107. 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 Z36249_PEA_3_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs
As noted above, cluster Z36249 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 Z36249_PEA_3_node_0 according to the present invention is supported by 42 libraries. The number of hbranes was determined as previously described. This segment can be found in the following transcript(s): Z36249_PEA_3_T2, Z36249 PEA 3 T3, Z36249_PEA_3_T5 and Z36249_PEA_3_ T9. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts
335
Segment cluster Z36249_PEA_3_node_3 according to the present invention is supported by 45 libraries The number of libraπes was determined as previously described This segment can be found in the following transcπpt(s) Z36249_PEA_3_T2, Z36249_PEA_3_T3, Z36249_PEA_3_T5 and Z36249_PEA_3_T9 Table 13 below descnbes the starting and ending position of this segment on each transcnpt Table 13 - Segment location on transcripts
Segment cluster Z36249_PEA_3_node_5 according to the present invention is supported by 34 hbranes The number of hbranes was detennined as previously described This segment can be found in the following transcπpt(s) Z36249_PEA_3_T2, Z36249_PEA_3_T3, Z36249_PEA_3_T5 and Z36249_PEA_3_T9 Table 14 below descnbes the starting and ending position of this segment on each transcnpt Table 14 - Segment location on transcripts
339
Segment cluster Z36249_PEA_3_node_l 1 according to the present invention is supported by 4 libraries The number of libranes was detennined as previously described. This segment can be found in the following transcπpt(s): Z36249 PEA 3 T5. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts
Segment cluster Z36249_PEA_3_node_14 according to the present invention is supported by 5 libraries. The number of hbraπes was detennined as previously descπbed. This segment can be found in the following transcript(s): Z36249 PEA 3 T3. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
Segment cluster Z36249_PEA_3_node_24 according to the present invention is supported by 34 libranes. The number of libranes was detennined as previously descπbed. This segment can be found in the following transcript(s): Z36249 PEA 3 T2 and Z36249_PEA_3_T9. Table 17 below describes the starting and ending position of this segment on each transcript. 340 Table 17 - Segment location on transcripts
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 Z36249_PEA_3_node_10 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): Z36249 PEA 3 T3, Z36249_PEA_3_T5 and Z36249_PEA_3_T9. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts
Segment cluster Z36249_PEA_3_node_13 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): Z36249_PEA_3_T2 and Z36249_PEA_3_T3. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts 34 1
Segment cluster Z36249_PEA_3_node_17 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): Z36249_PEA_3_T2 and Z36249_PEA_3_T9. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster Z36249_PEA_3_node_19 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): Z36249_PEA_3_T2 and Z36249_PEA_3_T9. Table 21 below describes the starting and ending position of this segment on each transcript. 7αt>/e 21 - Segment location on transcripts
Segment cluster Z36249_PEA_3_node_21 according to the present invention is supported 342 by 18 libraπes The number of libraries was determined as previously descπbed This segment can be found in the following transcπpt(s)- Z36249_PEA_3_T2 and Z36249_PEA_3_T9 Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: Q96LE7
Sequence documentation:
Alignment of: Z36249 PEA 3 P2 x Q96LE7
Alignment segment 1/1:
Quality: 2639.00 Escore: 0 Matching length: 283 Total length: 319 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 88.71 Total Percent Identity: 88.71 Gaps : 1
Alignment :
1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50
51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I II II I I I I I I I I I I I I II I I I I II I I I I I I I I I I I I I I II I I I I I II II 51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 343
101 KTKVPVVKEPEPEII 115 I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 . . . . . 116 . YKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIH ASRGGNLD 164 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLD 200 165 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 214 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I 201 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 250
215 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 264 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I 251 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 300
265 AIFDSLRENSYKTSRIATF 283 I I I II I I I I I I I I II I I I I 301 AIFDSLRENSYKTSRIATF 319
Sequence name: Q15327
Sequence documentation:
Alignment of: Z36249_PEA_3_P2 x Q15327
Alignment segment 1/1: Quality: 2626.00 Escore: 0 Matching length: 283 Total length: 319 Matching Percent Similarity: 99.65 Matching Percent Identity: 99.65 Total Percent Similarity: 88.40 Total Percent Identity: 88.40 Gaps : 1
Alignment :
1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 344 II I I I I I I I I I II I I I I I I I I I I I I I I II I I I I I I II I I I I I I I II II I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I I I I I I I I I M I I I I I I I I I I I I I I I I I I I I I I I I I I M I I I I I I I II I 51 HPVTLGEQQ KSEKQREAELPKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100
101 KTKVPVVKEPEPEII 115 I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
116 .YKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIH ASRGGNLD 164 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIH ASRGGNLD 200 . . . . . 165 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 214 I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I 201 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 250 215 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 264 I I I I I II I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I II I I I I I I I I I 251 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 300
265 AIFDSLRENSYKTSRIATF 283 I I I II I I I I II I I II I I I I 301 AIFDSLRENSYKTSRIATF 319
Sequence name: Q96LE7
Sequence documentation:
Alignment of: Z36249_PEA_3_P3 x Q96LE7
Alignment segment 1/1:
Quality: 1785.00 Escore: 0 Matching length: 184 Total length: 184 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 345 Total Percent Simi lari ty : 100 . 00 Tota l Percent I dentity : 100 . 00 Gaps : 0
Al ignment : . . . . . 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 HPVTLGEQQ KSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100
101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 I I II I I I I I I I I I I I I II I II I I I II I I I I II I I I I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDM 184 I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I 151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDM 184
Sequence name: Q15327
Sequence documentation:
Alignment of: Z36249_PEA_3_P3 x Q15327
Alignment segment 1/1:
Quality: 1772.00 Escore: 0 Matching length: 184 Total length: 184 Matching Percent Similarity: 99.46 Matching Percent Identity: 99.46 Total Percent Similarity: 99.46 Total Percent Identity: 99.46 Gaps: 0
Alignment :
1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 34 6 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50
51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I I I II I I I I I II I I I I I I I I I I I II I I I I I I I I I I II I I I I I I I I I I I I 51 HPVTLGEQQ KSEKQREAELPKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100
101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDM 184 I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDM 184
Sequence name: Q96LE7
Sequence documentation:
Alignment of: Z36249_PEA_3_P4 x Q96LE7
Alignment segment 1/1:
Quality: 1464.00 Escore: 0 Matching length: 151 Total length: 151 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment:
1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50
51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I II I I I I I I 51 HPVTLGEQQ KSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 347 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 I I I I I I I I I I I I I II I I I I II I I I I I I I I II I I I I I I I I I I I I I I I II I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
151 E 151 I 151 E 151
Sequence name: Q15327
Sequence documentation:
Alignment of: Z36249_PEA_3_P4 x Q15327
Alignment segment 1/1:
Quality: 1451.00 Escore: 0 Matching length: 151 Total length: 151 Matching Percent Similarity: 99.34 Matching Percent Identity: 99.34 Total Percent Similarity: 99.34 Total Percent Identity: 99.34 Gaps: 0
Alignment :
1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I II I I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 51 HPVTLGEQQ KSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I I I I II I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 HPVTLGEQQWKSEKQREAELPKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100
101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
151 E 151 348 I 151 E 151
Sequence name: Q96LE7
Sequence documentation:
Alignment of: Z362 9_PEA_3_P5 x Q96LE7
Alignment segment 1/1:
Quality: 2670.00 Escore: 0 Matching length: 286 Total length: 319 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 89.66 Total Percent Identity: 89.66 Gaps : 1
Alignment : 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I II I I I I I I I I I I I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50
51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I II I I 51 HPVTLGEQQ KSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100
101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
151 E LESTAIHWASRGGNLD 167 I I I I I I I I I I I I I I I I I 151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLD 200
168 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 217 I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I II I I II I I I I I I 201 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 250 34 9 218 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 2 67 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 251 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 300
268 AIFDSLRENSYKTSRIATF 286 I I I I I I I I I I I I I I I I I II 301 AIFDSLRENSYKTSRIATF 319
Sequence name: Q15327
Sequence documentation:
Alignment of: Z36249_PEA_3_P5 x Q15327
Alignment segment 1/1:
Quality: 2657.00 Escore: 0 Matching length: 286 Total length: 319 Matching Percent Similarity: 99.65 Matching Percent Identity: 99.65 Total Percent Similarity: 89.34 Total Percent Identity: 89.34 Gaps : 1
Alignment :
1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I II I I I II II I I I I I I I I 1 MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLA 50 51 HPVTLGEQQWKSEKQREAELKKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I II I I II I I I 51 HPVTLGEQQ KSEKQREAELPKKKLEQRSKLENLEDLEIIIQLKKRKKYR 100
101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150 I II I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 KTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCD 150
151 E LESTAIHWASRGGNLD 167 350 I I I I I I II I I I I I I I I I 151 EYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLD 200
168 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 217 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 201 VLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDR 250
218 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 267 II I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I II I I I I I I I I I I I I I I 251 EGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTK 300
268 AIFDSLRENSYKTSRIATF 286 I I I I I II I I I I I I I I II I I 301 AIFDSLRENSYKTSRIATF 319
DESCRIPTION FOR CLUSTER Z25377 Cluster Z25377 features 9 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
351
Table 2 - Segments oj interest jSegment Name
Z25377 PEA 1 node 5 197
Z25377 PEA 1 node 12 198
Z25377 PEA 1 node 15 199
Z25377 PEA 1 node 17 200
Z25377 PEA 1 node 18 201
Z25377 PEA 1 node 22 202
Z25377 PEA 1 node 24 203
Z25377 PEA 1 node 0 204
Z25377 PEA 1 node 7 205
Z25377 PEA 1 node 8 206
Z25377 PEA 1 node 10 207
Z25377 PEA 1 node 20 208
Table 3 - Proteins of interest
Z25377 PEA 1 P12 317 Z25377 PEA 1 Til
Z25377 PEA 1 PI3 318 Z25377 PEA 1 T12
Z25377 PEA 1 P14 319 Z25377 PEA 1 T13
Z25377 PEA 1 PI5 320 Z25377 PEA 1 TI
Z25377 PEA 1 P17 321 Z25377 PEA 1 T5
Z25377 PEA 1 PI8 322 Z25377 PEA 1 T7
Z25377 PEA 1 P19 323 Z25377 PEA 1 T8
Z25377 PEA 1 P20 324 Z25377 PEA 1 T9
Z25377 PEA 1 P21 325 Z25377 PEA 1 T10
These sequences are variants of the known protein Hypothetical protein FLJ26352 (SwissProt accession identifier Q6ZP80; known also according to the synonyms RLNI6974), 352 refeπed to herein as the previously known protein. The sequence for protein Hypothetical protein FLJ26352 is given at the end of the application, as "Hypothetical protein FLJ26352 amino acid sequence" (SEQ ID NO:390). The heart-selective diagnostic marker prediction engine provided the following results with regard to cluster Z25377. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the y-axis of Figure 29 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 histogram in
Figure 29, concerning the number of heart-specific clones in libraries/sequences. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non-heart ESTs, which was found to be 13.3; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 4.9; and fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 6.50E-07. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 13.3, which clearly supports specific expression in heart tissue. As noted above, cluster Z25377 features 9 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Hypothetical protein FLJ26352. A description of each variant protein according to the present invention is now provided. Variant protein Z25377_PEA_1_P12 according to the present invention has an amino acid 353 sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T11. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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 Z25377_PEA_1_P12 and BAC85244 (SEQ ID NO:341): l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P12, comprising a first amino acid sequence being at least 90 % homologous to MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRC WFNGIVEENDSNIWKFWYTNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWA VLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGI coπesponding to amino acids 1 - 158 of BAC85244, which also coπesponds to amino acids 1 - 158 of Z25377 PEA 1 P12.
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 Z25377_PEA_1_P12 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 Z25377_PEA_1_P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 4 - Amino acid mutations
Variant protein Z25377_PEA_1_P12 is encoded by the following transcript(s): Z25377_PEA_1_T11, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T1 1 B shown in bold; this coding portion starts at position 188 and ends at position 661. 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 Z25377 PEA 1 P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Nucleic acid SNPs
Variant protein Z25377_PEA_1_P13 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T12. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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: 355
Comparison report between Z25377_PEA_1_P13 and BAC85244: l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P13, comprising a first amino acid sequence being at least 90 % homologous to MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRC WFNGIVEENDSNIWKFWYTNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWA VLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAA coπesponding to amino acids 1 - 156 of BAC85244, which also coπesponds to amino acids 1 - 156 of Z25377_PEA_1_P13, 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 VSVGQECGSG conesponding to amino acids 157 - 166 of Z25377_PEA_1_P13, 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 Z25377_PEA_1_P13, 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 VSVGQECGSG in Z25377_PEA_1_P13.
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 Z25377_PEA_1_P13 is encoded by the following transcript(s):
Z25377_PEA_1_T12, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T12 is shown in bold; this coding portion starts at position 188 and ends at position 685. The transcript also has the following SNPs as listed in
Table 6 (given according to their position on the nucleotide sequence, with the alternative 356 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25377_PEA_1_P13 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs
Variant protein Z25377 PEA 1 P14 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T13. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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 Z25377_PEA_1_P14 and BAC85244: l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P14, comprising a first amino acid sequence being at least 90 % homologous to MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRC WFNGIVEENDSNIWKFWYTNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWA VLMLLGVVAVVIASFLI1CAAPFASHFLYKAGGGSYIAA conesponding to amino acids 1 - 156 of BAC85244, which also coπesponds to amino acids 1 - 156 of Z25377_PEA_1_P14, 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY coπesponding to amino acids 157 - 210 of Z25377_PEA_1_P14, wherein said first amino acid 357 sequence and second amino acid sequence are contiguous and in a sequential order. 2. An isolated polypeptide encoding for a tail of Z25377_PEA_1_P14, 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 DGISSLCYSSLSKSLLSQPLRETSSAIND1SLLQALMPLLGWTSHWTCITVGLY in Z25377 PEA 1 P14.
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 fo llows 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 Z25377_PEA_ 1JP14 is encoded by the following transcript(s): Z25377_PEA_1_T13, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T13 is shown in bold; this coding portion starts at position 188 and ends at position 817. 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 Z25377_PEA_1_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs
358
Variant protein Z25377_PEA_1_P15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T1. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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 Z25377_PEA_1_P15 and Q96NR4 (SEQ ID NO:342): l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P15, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIA A coπesponding to amino acids 1 - 60 of Q96NR4, which also conesponds to amino acids 1 - 60 of Z25377_PEA_1_P15, 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
DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY coπesponding to amino acids 61 - 114 of Z25377_PEA_1_P15, 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 Z25377_PEA_1_P15, comprising a polypeptide being at least 10%, 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY in Z25377_PEA_l_P15.
Comparison report between Z25377JPEA 1 P15 and BAC85244: l.An isolated chimeric polypeptide encoding for Z25377 PEA 1 P15, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIA 359 A coπesponding to amino acids 97 - 156 of BAC85244, which also corresponds to amino acids 1 - 60 of Z25377_PEA_1_P15, 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY conesponding to amino acids 61 - 114 of Z25377_PEA_1_P15, 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 Z25377_PEA_1_P15, 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 DGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY in Z25377 PEA 1 PI 5.
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 the Signalp_hmm software predicts that this protein has a signal anchor region. Variant protein Z25377_PEA_1_P15 is encoded by the following transcript(s): Z25377_PEA_1_T1, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T1 is shown in bold; this coding portion starts at position 261 and ends at position 602. 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 Z25377_PEA_1_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs
360
Variant protein Z25377_PEA_1_P17 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T5. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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 Z25377_PEA_1_P17 and Q96NR4: l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P17, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDSAV conesponding to amino acids 1 - 14 of Q96NR4, which also coπesponds to amino acids 1 - 14 of Z25377_PEA_1_P17, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to ILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAG LLFLVVGRHIQIHH coπesponding to amino acids 62 - 133 of Q96NR4, which also corresponds to amino acids 16 - 87 of Z25377 PEA 1 P17, 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 polypeptide encoding for an edge portion of Z25377_PEA_1_P17, 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 VSI having a structure as follows (numbering according to Z25377_PEA_1_P17): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((n-2) - x), in which x varies from 0 to n-2. 361
Comparison report between Z25377_PEA_1_P17 and Q8WW45 (SEQ ID NO:343): l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P17, 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 MRGEHNSTSYDSAVS coπesponding to amino acids 1 - 15 of Z25377_PEA_1_P17, and a second amino acid sequence being at least 90 % homologous to ILFSLVVMLYV1WVQAVADMESYRNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAG LLFLVVGRHIQIHH "coπesponding to amino acids 39 - 110 of Q8WW45, which also corresponds to amino acids 16 - 87 of Z25377_PEA_1_P17, 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 Z25377 PEA 1 P17, 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 MRGEHNSTSYDSAVS of Z25377_PEA_1_P17.
Comparison report between Z25377_PEA_1_P17 and BAC85244: l.An isolated chimeric polypeptide encoding for Z25377_PEA_1_P17, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDS AV conesponding to amino acids 97 - 1 10 of BAC85244, which also coπesponds to amino acids 1 - 14 of Z25377_PEA_1_P17, a second amino acid sequence bridging amino acid sequence comprising of S, and a third amino acid sequence being at least 90 % homologous to ILFSLVVMLYVIWVQAVADMESYRJNTMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAG LLFLVVGRHIQIHH coπesponding to amino acids 158 - 229 of BAC85244, which also coπesponds to amino acids 16 - 87 of Z25377 PEA 1 P17, 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 polypeptide encoding for an edge portion of Z25377_PEA_1_P17, 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 362 least about 50 amino acids in length, wherein at least two amino acids comprise VSI having a structure as follows (numbering according to Z25377_PEA_1_P17): a sequence starting from any of amino acid numbers 14-x to 14; and ending at any of amino acid numbers 16 + ((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 it is a partial protein, because both trans-membrane region prediction programs predict that this protein has a trans- membrane region.
Variant protein Z25377_PEA_1_P17 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 rot; the presence of known SNPs in variant protein Z25377_PEA_1_P17 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations
Variant protein Z25377_PEA_1_P17 is encoded by the following transcript(s): Z25377_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T5 is shown in bold; this coding portion starts at position 261 and ends at position 521. 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 363 known SNPs in variant protein Z25377_PEA_1_P 17 sequence provides support for the deduced sequence of this variant protein according to the present invention) Table 10 - Nucleic acid SNPs
Variant protein Z25377 PEA 1 P18 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T7. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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 Z25377_PEA_1_P18 and Q96NR4. l.An isolated chimeric polypeptide encoding for Z25377_PEA_1_P18, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAWIASFLIICAAPFASHFLYKAGGGSYIA AGI coπesponding to amino acids 1 - 62 of Q96NR4, which also coπesponds to amino acids 1 - 62 of Z25377 PEA 1 PI 8. 364
Comparison report between Z25377_PEA_1_P18 and Q8WW45: l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P18, 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 MRGEHNSTSYDSAVIYRGFWAVL coπesponding to amino acids 1 - 23 of Z25377_PEA_1_P18, and a second amino acid sequence being at least 90 % homologous to MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGI coπesponding to amino acids 1 - 39 of Q8WW45, which also coπesponds to amino acids 24 - 62 of Z25377 PEA 1JP18, 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 Z25377_PEA_1_P18, 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 MRGEHNSTSYDSAVIYRGFWAVL of Z25377_PEA_1_P18.
Comparison report between Z25377_PEA_1_P18 and BAC85244: l.An isolated chimeric polypeptide encoding for Z25377_PEA_1_P18, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIA AGI conesponding to amino acids 97 - 158 of BAC85244, which also conesponds to amino acids 1 - 62 of Z25377_PEA_1_P18.
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 the Signalp hmm software predicts that this protein has a signal anchor region. Variant protein Z25377_PEA_1_P18 also has the following non-silent SNPs (Single
Nucleotide Polymoφhisms) as listed in Table 11 , (given according to their position(s) on the 365 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 Z25377_PEA_1_P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations
Variant protein Z25377_PEA_1_P18 is encoded by the following transcript(s): Z25377_PEA_1_T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T7 is shown in bold; this coding portion starts at position 261 and ends at position 446. 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 Z25377_PEA_1_P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs
Variant protein Z25377 PEA 1 P19 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T8. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP 366 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 Z25377_PEA_1_P19 is encoded by the following transcript(s): Z25377_PEA_1_T8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T8 is shown in bold; this coding portion starts at position 127 and ends at position 261. 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 Z25377_PEA_1_P19 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Nucleic acid SNPs
Variant protein Z25377_PEA_1_P20 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25377_PEA_1_T9. An alignment is given to the known protein (Hypothetical protein FLJ26352) 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 Z25377_PEA_1_P20 and Q96NR4: 367 l .An isolated chimeric polypeptide encoding for Z25377_PEA_1_P20, comprising a first amino acid sequence being at least 90 % homologous to MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIA A coπesponding to amino acids 1 - 60 of Q96NR4, which also coπesponds to amino acids 1 - 60 of Z25377_PEA_1_P20, 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%o homologous to a polypeptide having the sequence VSVGQECGSG corresponding to amino acids 61 - 70 of Z25377_PEA_1_P20, 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 Z25377_PEA_1_P20, 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 VSVGQECGSG in Z25377_PEA_1_P20. Comparison report between Z25377_PEA_1_P20 and Q8WW45: l.An isolated chimeric polypeptide encoding for Z25377 PEA 1 P20, 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 MRGEHNSTSYDSAVIYRGFWAVL corresponding to amino acids 1 - 23 of Z25377_PEA_1_P20, a second amino acid sequence being at least 90 % homologous to MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAA coπesponding to amino acids 1 - 37 of Q8WW45, which also coπesponds to amino acids 24 - 60 of Z25377_PEA_1_P20, 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 VSVGQECGSG coπesponding to amino acids 61 - 70 of Z25377 PEA 1 P20, 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 polypeptide encoding for a head of Z25377_PEA_1_P20, 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 MRGEHNSTSYDSAVIYRGFWAVL of Z25377_PEA_1_P20. 368 3. An isolated polypeptide encoding for a tail of Z25377_PEA_1_P20, 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 VSVGQECGSG in Z25377_PEA_1_P20.
Comparison report between Z25377_PEA_1_P20 and BAC85244: 1.An isolated chimeric polypeptide encoding for Z25377_PEA_1_P20, comprising a first amino acid sequence being at least 90 %> homologous to MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIA A coπesponding to amino acids 97 - 156 of BAC85244, which also conesponds to amino acids 1 - 60 of Z25377_PEA_1_P20, 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%o homologous to a polypeptide having the sequence VSVGQECGSG corresponding to amino acids 61 - 70 of Z25377_PEA_1_P20, 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 Z25377_PEA_1_P20, 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 VSVGQECGSG in Z25377_PEA_1_P20.
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 the Signalp hmm software predicts that this protein has a signal anchor region. Variant protein Z25377_PEA_1_P20 is encoded by the following transcript(s): Z25377_PEA_1_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T9 is shown in bold; this coding portion starts at position 261 and ends at position 470. Variant protein Z25377_PEA_1_P21 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 369 Z25377_PEA_1_T10. 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 Z25377_PEA_1_P21 is encoded by the following transcript(s): Z25377JPEA_1_T10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25377_PEA_1_T10 is shown in bold; this coding portion starts at position 261 and ends at position 464. 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 Z25377_PEA_1_P21 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs
As noted above, cluster Z25377 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 Z25377_PEA_l_node_5 according to the present invention is supported 370 by 1 libraries The number of libranes was determined as previously described This segment can be found in the following transcπpt(s) Z25377_PEA_1_T11 , Z25377_PEA_1_T12 and Z25377_PEA_1_T13 Table 15 below describes the starting and ending position of this segment on each transcript Table 15 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_12 according to the present invention is supported by 2 libraries. The number of libranes was detennined as previously descnbed. This segment can be found in the following transcπpt(s): Z25377_PEA_1_T8. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_15 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 followmg transcπpt(s): Z25377_PEA_1_T1, Z25377_PEA_1_T7, Z25377_PEA_1_T9, Z25377_PEA_1_T11, Z25377_PEA_1_T12 and Z25377_PEA_1_T13. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts 371 Transcript name Segment Segment starting position endingfposition Z25377 PEA 1 TI 304 441 Z25377 PEA 1 T7 304 441 Z25377 PEA 1 T9 304 441 Z25377 PEA 1 Ti l 519 656 Z25377 PEA 1 T12 519 656 Z25377 PEA 1 T13 519 656
Segment cluster Z25377_PEA_l_node_17 according to the present invention is supported by 16 libraries. The number of libraπes was determined as previously described. This segment can be found m the following transcπpt(s): Z25377_PEA_1_T5. Table 18 below describes the starting and ending position of this segment on each transcnpt. Table 18 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_l 8 according to the present invention is supported by 55 libraries. The number of libraries was determined as previously descπbed. This segment can be found in the following transcript(s): Z25377_PEA_1_T5. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts
372
Segment cluster Z25377_PEA_l_node_22 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): Z25377_PEA_1_T1 , Z25377JPEA_1_T7, Z25377_PEA_1_T10, Z25377_PEA_1_T1 1 and Z25377_PEA_1_T13. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_24 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): Z25377_PEA_1_T9 and Z25377_PEA_1_T12. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts
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. 373
Segment cluster Z25377_PEA_l_node_0 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): Z25377_PEA_1_T1 , Z25377_PEA_1_T5, Z25377_PEA_1_T7, Z25377_PEA_1_T8, Z25377_PEA_1_T9 and Z25377_PEA_1_T10. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_7 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): Z25377_PEA_1_T1, Z25377_PEA_1_T5, Z25377_PEA_ 1_T7, Z25377_PEA_1_T8, Z25377_PEA_1_T9, Z25377_PEA_1_T10, Z25377_PEA_1_T11, Z25377_PEA_1_T12 and Z25377_PEA_1_T13. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts
374
Segment cluster Z25377_PEA_l_node_8 according to the present invention can be found in the following transcript(s): Z25377_PEA_1_T1, Z25377_PEA_1_T5, Z25377_PEA_1_T7, Z25377_PEA_1_T8, Z25377_PEA_1_T9, Z25377_PEA_1_T10, Z25377_PEA_1_T11, Z25377_PEA_1_T12 and Z25377_PEA_1_T13. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_10 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): Z25377_PEA_1_T1, Z25377_PEA_1_T5, 375 Z25377_PEA_1_T7, Z25377_PEAJ_T8, Z25377 PEAJ T9, Z25377_PEA_1_T10, Z25377_PEA_1_T1 1 , Z25377_PEA_l_ri2 and Z25377_PEA_1_T13 Table 25 below describes the starting and ending position of this segment on each transcπpt Table 25 - Segment location on transcripts
Segment cluster Z25377_PEA_l_node_20 according to the present invention is supported by 1 libraπes The number of libranes was detennined as previously descπbed This segment can be found in the following transcπpt(s) Z25377_PEA_1_T7 and Z25377_PEA_1_T11. Table 26 below descnbes the starting and ending position of this segment on each transcript Table 26 - Segment location on transcripts
Variant protein alignment to the previously known protein 376 Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P12 x BAC85244
Alignment segment 1/1:
Quality: 1575.00 Escore: 0 Matching length: 158 Total length: 158 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment:
1 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTF 50 I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTF 50 . . . . . 51 HHEGFFWRCWFNGIVEENDSNI KF YTNQPPSKNCTHAYLSPYPFMRGE 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I 51 HHEGFF RCWFNGIVEENDSNI KFWYTNQPPSKNCTHAYLSPYPFMRGE 100 101 HNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGG 150 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I II I II I I I 101 HNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGG 150
151 GSYIAAGI 158 I I I I I I I I 151 GSYIAAGI 158
Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P13 x BAC85244 377
Alignment segment 1/1:
Quality: 1558.00 Escore: 0 Matching length: 156 Total length: 156 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTF 50 I II I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTF 50
51 HHEGFFWRCWFNGIVEENDΞNI KFWYTNQPPSKNCTHAYLSPYPFMRGE 100 I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 HHEGFFWRCWFNGIVEENDSNIWKF YTNQPPSKNCTHAYLSPYPFMRGE 100 101 HNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGG 150 I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I 101 HNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGG 150
151 GSYIAA 156 I I I I I I 151 GSYIAA 156
Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P14 x BAC85244
Alignment segment 1/1:
Quality: 1559.00 Escore: 0 Matching length: 162 Total length: 162 Matching Percent Similarity: 98.15 Matching Percent Identity: 97.53 378 Total Percent Simi lari ty : 98 . 15 Total Pe rcent I denti ty : 97 . 53 Gaps : 0
Al ignment : . . . . . 1 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTF 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I II I I I I I I I I I I I 1 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTF 50 51 HHEGFFWRCWFNGIVEENDSNIWKFWYTNQPPSKNCTHAYLSPYPFMRGE 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 HHEGFFWRCWFNGIVEENDSNI KF YTNQPPSKNCTHAYLSPYPFMRGE 100
101 HNSTSYDSAVIYRGFWAVLMLLGVVAVV1ASFLIICAAPFASHFLYKAGG 150 I I I I I I I I I I II I I I I I I II I II I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 HNSTSYDSAVIYRGF AVLMLLGVVAVVIASFLIICAAPFASHFLYKAGG 150
151 GSYIAADGISSL 162 I I I I I I : I I 151 GSYIAAGILFSL 162
Sequence name: Q96NR4
Sequence documentation:
Alignment of: Z25377_PEA_1_P15 x Q96NR4
Alignment segment 1/1: Quality: 572.00 Escore: 0 Matching length: 66 Total length: 66 Matching Percent Similarity: 95.45 Matching Percent Identity: 93.94 Total Percent Similarity: 95.45 Total Percent Identity: 93.94 Gaps: 0
Alignment :
1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50 379 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MRGEHNSTSYDSAVIYRGF AVLMLLGVVAVVIASFLIICAAPFASHFLY 50
51 KAGGGSYIAADGISSL 66 I I I I I I I I I I : I I 51 KAGGGSYIAAGILFSL 66
Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P15 x BAC85244
Alignment segment 1/1:
Quality: 572.00 Escore: 0 Matching length: 66 Total length: 66 Matching Percent Similarity: 95.45 Matching Percent Identity: 93.94 Total Percent Similarity: 95.45 Total Percent Identity: 93.94 Gaps: 0
Alignment :
1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I 97 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 146
51 KAGGGSYIAADGISSL 66 I I I I I I I I I I : II 147 KAGGGSYIAAGILFSL 162
Sequence name: Q96NR4
Sequence documentation:
Alignment of: Z25377_PEA_1_P17 x Q96NR4
Alignment segment 1/1 : 380
Quality: 744.00 Escore: 0 Matching length: 87 Total length: 133 Matching Percent Similarity: 98.85 Matching Percent Identity: 98.85 Total Percent Similarity: 64.66 Total Percent Identity: 64.66 Gaps : 1
Alignment : 1 MRGEHNSTSYDSAV 14 I I I I I I I I I I I I I I 1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50
15 SILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVL 54 I I I M I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 KAGGGSYIAAGILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVL 100
55 YGWSFFLAPAGIFFSLLAGLLFLVVGRHIQIHH 87 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I 101 YG SFFLAPAGIFFSLLAGLLFLVVGRHIQIHH 133
Sequence name: Q8 W45
Sequence documentation:
Alignment of: Z25377_PEA_1_P17 x Q8 W45
Alignment segment 1/1: Quality: 711.00 Escore: 0 Matching length: 75 Total length: 75 Matching Percent Similarity: 97.33 Matching Percent Identity: 97.33 Total Percent Similarity: 97.33 Total Percent Identity: 97.33 Gaps : 0
Alignmen :
13 AVSILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVLYGWSFFLA 62 381 I I I I I I I I II I I I I I I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I 36 AAGILFSLVVMLYVI VQAVADMESYRNMKMKDCLDFTPSVLYG SFFLA 85
63 PAGIFFSLLAGLLFLVVGRHIQIHH 87 I I I I I I II I II I II I I I I I I II I I I 86 PAGIFFSLLAGLLFLVVGRHIQIHH 110
Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P17 x BAC85244
Alignment segment 1/1:
Quality: 744.00 Escore: 0 Matching length: 87 Total length: 133 Matching Percent Similarity: 98.85 Matching Percent Identity: 98.85 Total Percent Similarity: 64.66 Total Percent Identity: 64.66 Gaps: 1
Alignment :
1 MRGEHNSTSYDSAV 14 I I II I I I I I I I I I I 97 MRGEHNSTSYDSAVIYRGF AVLMLLGVVAVVIASFLIICAAPFASHFLY 146
15 SILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVL 54 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I 147 KAGGGSYIAAGILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVL 196
55 YGWSFFLAPAGIFFSLLAGLLFLVVGRHIQIHH 87 I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I 197 YGWSFFLAPAGIFFSLLAGLLFLVVGRHIQIHH 229
Sequence name: Q96NR4
Sequence documentation: 382
Alignment of: Z25377_PEA_1_P18 x Q96NR4
Alignment segment 1/1:
Quality: 588.00 Escore: 0 Matching length: 62 Total length: 62 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50 I I M I I I I I I I I II I I I I I M I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50
51 KAGGGSYIAAGI 62 I I I I I I I I I I I I 51 KAGGGSYIAAGI 62
Sequence name: Q8WW45
Sequence documentation:
Alignment of: Z25377_PEA_1_P18 x Q8WW45
Alignment segment 1/1: Quality: 358.00 Escore: 0 Matching length: 39 Total length: 39 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
24 MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGI 62 383 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGI 39
Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P18 x BAC85244
Alignment segment 1/1:
Quality: 588.00 Escore: 0 Matching length: 62 Total length: 62 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment : 1 MRGEHNSTSYDSAVIYRGF AVLMLLGVVAVVIASFLIICAAPFASHFLY 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 97 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 146
51 KAGGGSYIAAGI 62 I I I I I I I I I I I I 147 KAGGGSYIAAGI 158
Sequence name: Q96NR4
Sequence documentation:
Alignment of: Z25377_PEA_1_P20 x Q96NR4
Alignment segment 1/1:
Quality: 571.00 Escore: 0 Matching length: 60 Total length: 60 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 384 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
1 MRGEHNSTSYDSAVIYRGF AVLMLLGVVAVVIASFLIICAAPFASHFLY 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50
51 KAGGGSYIAA 60 I I I I I I I I I I 51 KAGGGSYIAA 60
Sequence name: Q8W 45
Sequence documentation:
Alignment of: Z25377_PEA_1_P20 x Q8WW45
Alignment segment 1/1:
Quality: 341.00 Escore: 0 Matching length: 37 Total length: 37 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment : 24 MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAA 60 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAA 37
Sequence name: BAC85244
Sequence documentation:
Alignment of: Z25377_PEA_1_P20 x BAC85244 385
Al ignment segment 1 / 1 :
Quality : 571.00 Escore: 0 Matching length: 60 Total length: 60 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
1 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 50 I I I I I II I I I I I I I I I I I I I I I I I I II I II I I I I I I I I I I I I I I I I I I I I 97 MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLY 146
51 KAGGGSYIAA 60 I I I I I I I I I I 147 KAGGGSYIAA 156 DESCRIPTION FOR CLUSTER HSACMHCP Cluster HSACMHCP features 10 transcript(s) and 65 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
386
Table 2 - Segments of interest
387
388
Table 3 - Proteins of interest
These sequences are variants of the known protein Myosin heavy chain, cardiac muscle alpha isoform (SwissProt accession identifier MYH6 HUMAN; known also according to the synonyms MyHC-alpha), refeπed to herein as the previously known protein.
Protein Myosin heavy chain, cardiac muscle alpha isoform is known or believed to have 389 the following function(s): Muscle contraction. The sequence for protein Myosin heavy chain, cardiac muscle alpha isoform is given at the end of the application, as "Myosin heavy chain, cardiac muscle alpha isoform amino acid sequence" (SEQ ID NO:391). Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein
390
Protein Myosin heavy chain, cardiac muscle alpha isoform localization is believed to be Thick filaments of the myofibrils. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: muscle contraction; striated muscle contraction; muscle development, which are annotation(s) related to Biological Process; microfilament motor; actin binding; calmodulin binding; ATP binding, which are annotation(s) related to Molecular Function; and muscle myosin; muscle thick filament; myosin, 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/>. The heart- selective diagnostic marker prediction engine provided the following results with regard to cluster HSACMHCP. Predictions were made for selective expression of transcripts of this cluster in heart tissue, according to the previously described methods. The numbers on the yaxis of Figure 30 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 histogram in Figure 30, concerning the number of heart- specific clones in libraries/sequences; as well as with regard to the histogram in Figures 31-32, concerning the actual expression of oligonucleotides in various tissues, including heart. This cluster was found to be selectively expressed in heart for the following reasons: in a comparison of the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in non- heart ESTs, which was found to be 24; the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle-specific ESTs which was found to be 92.5; and fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant, and were found to be 391
3.20E-47. One particularly important measure of specificity of expression of a cluster in heart tissue is the previously described comparison of the ratio of expression of the cluster in heart as opposed to muscle. This cluster was found to be specifically expressed in heart as opposed to non-heart ESTs as described above. However, many proteins have been shown to be generally expressed at a higher level in both heart and muscle, which is less desirable. For this cluster, as described above, the ratio of expression of the cluster in heart specific ESTs to the overall expression of the cluster in muscle- specific ESTs which was found to be 24, which clearly supports specific expression in heart tissue. As noted above, cluster HSACMHCP features 10 transcript(s), which were listed in Table
1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Myosin heavy chain, cardiac muscle alpha isoform. A description of each variant protein according to the present invention is now provided. Variant protein HSACMHCP_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T2. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP_PEA_1_P2 and MYH6_HUMAN_V1 : l.An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P2, comprising a first amino acid sequence being at least 90 % homologous to MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGK VIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYT YSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSI LITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGN AKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNK KPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYK 392
LTGA1MHYGNMKFKQKQREEQΛEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVG NEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLDIAGF EIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEK PMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGT VDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKG SSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVL EGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGH TKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIR AFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEK MVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMN AELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKL TKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLE RAKRK -.EGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKK LKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKR EAEFQKMRRDLEEATLQHEATAAALRKKFIADSVAELGEQIDNLQRVKQKLEKEKSEF KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQT ENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDC DLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKJLAE WKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQ LGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIER KLAEKDEEMEQAK NHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSH ANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELR AVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC RNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIAL KGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQ coπesponding to amino acids 1 - 1855 of MYH6_HUMAN_V1, which also conesponds to amino acids 1 - 1855 of HSACMHCP_PEA_1_P2, 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT coπesponding to 393 amino acids 1856 - 1904 of HSACMHCP PEA 1 P2, 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 HSACMHCP_PEA_1_P2, 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT in HSACMHCP PEA 1 P2.
It should be noted that the known protein sequence (MYH6_HUMAN; SEQ ID NO:391) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYH6_HUMAN_V 1 (SEQ ID NO:338). These changes were previously known to occur and are listed in the table below. Table 5 - Changes to MYH6_HUMAN_V1
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 HSACMHCP_PEA_1_P2 is encoded by the following transcript(s): HSACMHCP PEA 1 T2, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP_PEA_1_T2 is shown in bold; this coding portion 394 starts at position 78 and ends at position 5789 The transcript also has the following SNPs as listed in Table 6 (given according to then 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 HSACMHCP PEA 1 P2 sequence provides support for the deduced sequence of this variant protein according to the present invention) Table 6 - Nucleic acid SNPs
395
Variant protein HSACMHCP_PEA_1_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T3. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP_PEA_1_P3 and MYH6_HUMAN_V2: l.An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P3, comprising a first amino acid sequence being at least 90 % homologous to MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGK VIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYT YSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSI LITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGN AKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNK KPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYK LTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVG NEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRTNATLETKQPRQYFIGVLDIAGF 396
EIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEK PMGIMSIL EEECMFPKATDMTFKAKL YDNH LGKSNNFQKPRNI KGKQE AHFS LIH Y AGT VDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKG SSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVL EGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGH TKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIR AFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEK MVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMN AELTAKXPJ LEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKL TKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLE RAKPJ LEGDLKLTQESIMDLENDKLQLEEK KKKEFDINQQNSKIEDEQALALQLQKK LKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKR EAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQT ENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGK corresponding to amino acids 1 - 1326 of MYH6_HUMAN_V2, which also coπesponds to amino acids 1 - 1326 of HSACMHCP PEA 1 P3, 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 VRPSGEGGQA corresponding to amino acids 1327 - 1336 of HSACMHCP PEA 1 P3, 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 HSACMHCP PEA 1 P3, 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 VRPSGEGGQA in HSACMHCP_PEA_1_P3.
It should be noted that the known protein sequence (MYH6 HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYH6 HUMAN V2 (SEQ ID NO:339). These changes were previously known to occur and are listed in the table below.
Table 7 - Changes to MYH6_HUMAN_V2 397 SNP position(s) on Type of change amino acid sequence 89 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: 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 HSACMHCP_PEA_1_P3 also has the following non- silent SNPs (Single Nucleotide Polymoφhisms) 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 HSACMHCP PEA 1 P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations
rnssmmm E -> Q Yes
376 P -> Q Yes 540 M -> R No 783 L -> M Yes 1101 A -> V Yes 1130 A -> T No 398 Variant protein HSACMHCP PEA 1 P3 is encoded by the following transcript(s): HSACMHCP PEA 1 T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP PEA 1 T3 is shown in bold; this coding portion starts at position 78 and ends at position 4085. 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 HSACMHCP PEA 1 P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs
399
Variant protein HSACMHCP PEA 1 P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T4. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP PEA 1 P4 and MYH6_HUMAN_V2: l .An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P4, comprising a first amino acid sequence being at least 90 % homologous to MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGK VIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEP A VLFNLKERYAAWMIYT YSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSI LITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGN AKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNK KPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYK LTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVG NEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRTNATLETKQPRQYFIGVLDIAGF EIFDFNSFEQLCIlN^TNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEK PMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGT VDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKG SSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVL EGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGH TKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIR AFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEK 400
MVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMN AELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKL TKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLE RAKRKLEGDLKLTQESIMDLENDKLQLEEKXKKKEFDINQQNSKIEDEQALALQLQKK LKENQARI EELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKR EAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQT ENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDC DLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAE WKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQ coπesponding to amino acids 1 - 1508 of MYH6 HUMAN V2, which also coπesponds to amino acids 1 - 1508 of HSACMHCP PEA 1 P4, 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 GVLGVQEARDELVGGRAMQGQGEHRL coπesponding to amino acids 1509 - 1534 of HSACMHCP PEA 1 P4, 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 HSACMHCP_PEA_1_P4, 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 GVLGVQEARDELVGGRAMQGQGEHRL in HSACMHCP_PEA_1_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: 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. 401
Variant protein HSACMHCP PEA 1 P4 also has the following non- silent SNPs (Single Nucleotide Polymoφhisms) as listed in Table 1 1 , (given according to their posιtιon(s) on the amino acid sequence, with the alternative amino acιd(s) listed, the last column indicates whether the SNP is known or not, the presence of known SNPs in vanant protein HSACMHCP PEA 1 P4 sequence provides support for the deduced sequence of this variant protein according to the present invention) Table 11 - Amino acid mutations
Vanant protein HSACMHCP PEA 1 P4 is encoded by the following transcπpt(s) HSACMHCP PEA 1 T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP_PEA_1_T4 is shown in bold; this coding portion starts at position 78 and ends at position 4679 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 vanant protein HSACMHCP_PEA_1_P4 sequence provides support for the deduced sequence of this vanant protem according to the present invention) Table 12 - Nucleic acid SNPs 402
Variant protein HSACMHCP_PEA_1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T7. An alignment is given to the known protein (Myosin heavy chain, 4 03 cardiac muscle alpha isoform) 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 HSACMHCP_PEA_1_P6 and MYH6J-IUMAN VI: l.An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P6, comprising a first amino acid sequence being at least 90 % homologous to
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGK VIAETENGKTVTVKEDQVLQQNPPKFDK1EDMAMLTFLHEPAVLFNLKERYAAWMI YT YSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSI LITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGN AKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNK KPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYK LTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVG NEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLDIAGF EIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEK PMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGT VDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKG SSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVL EGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGH TKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIR AFMGVKNWPWMKLYFKDKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEK MVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMN AELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKL TKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLE RAKPJ<X.EGDLKLTQESIMDLENDKLQLEEKLKKKEFDΓNQQNSKIEDEQALALQLQKK LKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKR EAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQT ENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDC 4 04
DLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAE WKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQ LGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIER KLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSH ANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELR AVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC RNAEEKAKKAITD conesponding to amino acids 1 - 1763 of MYH6 HUMAN V1 , which also coπesponds to amino acids 1 - 1763 of HSACMHCP PEA 1 P6, 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 VSDRPPSASPKDRNKALGPGQATVL coπesponding to amino acids 1764 - 1788 of HSACMHCP PEA 1 P6, 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 HSACMHCP PEA 1 P6, 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 VSDRPPSASPKDRNKALGPGQATVL in HSACMHCP_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: 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 HSACMHCP_PEA_1_P6 also has the following non-silent SNPs (Single
Nucleotide Polymoφhisms) 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 405 HSAC HCP_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention) Table 14 - Amino acid mutations
Variant protein HSACMHCP PEA 1 P6 is encoded by the following transcript(s): HSACMHCP PEA 1 T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP PEA 1 T7 is shown in bold; this coding portion starts at position 78 and ends at position 5441. The transcπpt 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 HSACMHCP PEA 1 P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 15 - Nucleic acid SNPs
406
407 Variant protein HSACMHCP PEA 1 P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP_PEA_1_T13. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP_PEA_1_P12 and MYH6 HUMAN V3 : l.An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P12, 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 MGLWKPGSVLSDSLFASSPCPQ coπesponding to amino acids 1 - 22 of HSACMHCP PEA 1 P12, and a second amino acid sequence being at least 90 % homologous to
PMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGT VDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKG SSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVL EGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGH TKVFFKAGLLGLLEEMRDERLS iTPxMQAQARGQLMRIEFKKIVERRDALLVIQWNIR AFMGVK^WPWMKLWKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEK MVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMN AELTAK-KJIKLEDECSELKK IDDLELTLAKVEKEKXIATENKVKNLTEEMAGLDEIIAKL TKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLE RAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKK LKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKR EAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQT ENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDC DLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAE 408 WKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEE1SDLTEQ LGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIER KLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSH ANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELR AVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC RNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIAL KGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLLR LQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKL RAKSRDIGAKQKMHDEE coπesponding to amino acids 528 - 1939 of MYH6_HUMAN_V3, which also coπesponds to amino acids 23 - 1434 of HSACMHCP PEA 1 P12, 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 HSACMHCP PEA 1 P12, 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 MGLWKPGSVLSDSLFASSPCPQ of HSACMHCP_PEA_1_P12.
It should be noted that the known protein sequence (MYH6_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYH6 HUMAN V3 (SEQ ID NO:340). These changes were previously known to occur and are listed in the table below. Table 16 - Changes to MYH6_HUMAN_V3
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: 409 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 HSACMHCP_PEA_1_P12 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HSACMHCP PEA 1 P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 17 - Amino acid mutations
Variant protein HSACMHCP_PEA_1_P12 is encoded by the following transcript(s): HSACMHCP PEA 1 T13, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP PEA 1 T13 is shown in bold; this coding portion starts at position 67 and ends at position 4368. 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 HSACMHCP PEA 1 P12 sequence provides 410 support for the deduced sequence of this variant protein according to the present invention). Table 18 - Nucleic acid SNPs
Variant protein HSACMHCP PEA 1 P16 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP_PEA_1_T17. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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: 4 1 1 Comparison report between HSACMHCP PEAJ P16 and MYH6 HUMAN V2: l .An isolated chimeric polypeptide encoding for HSACMHCP_PEA_1_P16, comprising a first amino acid sequence being at least 90 % homologous to MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGK VIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYT YSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSI LITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGN AKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNK KPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYK LTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVG NEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLDIAGF EIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEK coπesponding to amino acids 1 - 527 of MYH6 HUMAN V2, which also coπesponds to amino acids 1 - 527 of HSACMHCP PEA 1 P16, 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 VPPWPHHLCPLLCHPDKVVAESLLHPRN coπesponding to amino acids 528 - 555 of HSACMHCP PEA 1 P16, 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 HSACMHCP PEA 1 P16, 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 VPPWPHHLCPLLCHPDKVVAESLLHPRN in HSACMHCP_PEA_1_P16.
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 412 protein
Variant protein HSACMHCP_PEA_1_P16 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) as listed in Table 20, (given according to their posιtιon(s) on the amino acid sequence, with the alternative amino acιd(s) listed, the last column indicates whether the SNP is known or not, the presence of known SNPs in variant protein HSACMHCP PEA 1 P16 sequence provides support for the deduced sequence of this variant protein according to the present invention) Table 20 - Am o acid mutations
Variant protem HSACMHCP PEA P16 is encoded by the following transcπpt(s) HSACMHCP_PEA_1_T17, for which the sequence(s) is/are given at the end of the application The coding portion of transcript HSACMHCP_PEA_1_T17 is shown in bold, this coding portion starts at position 78 and ends at position 1742. The transcnpt also has the following SNPs as listed in Table 21 (given accordmg 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 vanant protein HSACMHCP_PEA_1_P16 sequence provides support for the deduced sequence of this vanant protein according to the present invention) Table 21 - Nucleic acid SNPs
413
Variant protein HSACMHCP PEA 1 P25 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T26. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP_PEA_1_P25 and MYH6_HUMAN_V1 : l .An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P25, comprising a first amino acid sequence being at least 90 % homologous to MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGK VIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEP A VLFNLKERYAAWMIYT YSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSI LITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGN AKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNK KPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYK LTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVG NEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLDIAGF EIFD conesponding to amino acids 1 - 470 of MYH6 HUMAN V1, which also coπesponds to amino acids 1 - 470 of HSACMHCP PEA 1 P25, a second amino acid sequence being at least 90 % homologous to PMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGT 4 14
VDYNILGWLEKNKDPLNETVVALYQKSSLKL ATLFSSYATADTGDSGKSKGGKKKG SSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVL EG1RICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGH TKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWN1R AFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEK MVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMN AELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKL TKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLE RAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKK LKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATS VQIEMNKKR EAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQT ENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDC DLLREQYEEETEAKA.ELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAE WKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQ LGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIER KLAEKTJEEMEQAKJWHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSH ANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELR AVVEQTERS11KLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC lWAEEKAKKAITDAAMMAEELKKEQDTSAHLEPxMKKNMEQTIKDLQHRLDEAEQIAL KGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQ coπesponding to amino acids 528 - 1855 of MYH6_HUMAN_V1, which also coπesponds to amino acids 471 - 1798 of HSACMHCP_PEA_1_P25, 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT coπesponding to amino acids 1799 - 1847 of HSACMHCP_PEA_1_P25, 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 415
HSACMHCP PEA 1 P25, 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 DP, having a structure as follows: a sequence starting from any of amino acid numbers 470-x to 470; and ending at any of amino acid numbers 471+ ((n-2) - x), in which x varies from 0 to n-2. 3.An isolated polypeptide encoding for a tail of HSACMHCP PEA 1 P25, 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 VRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT in
HSACMHCP PEA 1 P25.
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 HSACMHCP_PEA_1_P25 also has the following non- silent SNPs (Single Nucleotide Polymoφhisms) 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 HSACMHCP_PEA_1_P25 sequence provides support for the deduced sequence of this variant protein according to the present invention).
Table 23 - Amino acid mutations 4 16
Variant protein HSACMHCP_PEA_1_P25 is encoded by the following transcript(s): HSACMHCP_PEA_1_T26, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP PEA 1 T26 is shown in bold; this coding portion starts at position 78 and ends at position 5618. 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 HSACMHCP PEA 1 P25 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 24 - Nucleic acid SNPs
417
Variant protein HSACMHCP PEA 1 P28 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T8. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP_PEA_1_P28 and MYH6_HUM AN_V3 : 418 l .An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P28, comprising a first amino acid sequence being at least 90 %> homologous to MLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQA NPALEAFGNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNY HIFYQILSNKKPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFT SEEKAGVYKLTGA1MHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKG LCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQ YFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGM DLQACIDLIEKPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQE AHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDS GKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLV MHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLD IDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRD ALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSE ARRKELEEKM VSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNE RLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKFIATENKVKNLTEEM AGLDEIIAKLTKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQ EKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATS VQIEMNKJ J^AEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQ KLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFT TQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHA LQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAK KKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQR NFDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQ EEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEF NQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDL NEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNL LQAELEELRAWEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSE VEEAVQECRNAEEKAXKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHR LDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQT 419 EEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERAD IAESQVNKLRAKSRDIGAKQKMHDEE coπesponding to amino acids 165 - 1939 of MYH6 HUMAN V3, which also corresponds to amino acids 1 - 1775 of HSACMHCP PEA 1 P28.
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 HSACMHCP PEA 1 P28 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) 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 HSACMHCP PEA 1 P28 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 26 - Amino acid mutations
420
Variant protein HSACMHCP_PEA_1_P28 is encoded by the following transcπpt(s): HSACMHCP_PEA_1_T8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP PEA 1 T8 is shown in bold; this coding portion starts at position 12 and ends at position 5336. 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 HSACMHCP PEA 1 P28 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 27 - Nucleic acid SNPs
421
Variant protein HSACMHCP PEA 1 P29 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSACMHCP PEA 1 T14. An alignment is given to the known protein (Myosin heavy chain, cardiac muscle alpha isoform) 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 HSACMHCP PEAJ P29 and MYH6_HUMAN_V3: l.An isolated chimeric polypeptide encoding for HSACMHCP PEA 1 P29, comprising a first amino acid sequence being at least 90 %> homologous to MNKKPEAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEK EKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRA KLQTENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSA RHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLA QRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDK ILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISD LTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKA EIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNEMEI QLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAEL EELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLΓNQKKKMESDLTQLQSEVEEA VQEC1WAEEKAKKAITDAAMMAEELK -EQDTSAHLERMKKNMEQTIKDLQHRLDEA EQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDK KNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAES QVNKLRAKSRDIGAKQKMHDEE coπesponding to amino acids 1165 - 1939 of MYH6 HUMAN V3, which also coπesponds to amino acids 1 - 775 of HSACMHCP PEA 1 P29. 422
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 HSACMHCP PEA 1 P29 also has the following non-silent SNPs (Single Nucleotide Polymoφhisms) as listed 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 HSACMHCP PEA 1 P29 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 29 - Amino acid mutations
Variant protein HSACMHCP_PEA_1_P29 is encoded by the following transcript(s): HSACMHCP PEA 1 T14, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSACMHCP_PEA_1_T14 is shown in bold; this coding portion starts at position 150 and ends at position 2474. The transcript also has the following SNPs as listed in Table 30 (given according to their position on the nucleotide sequence, with the altemative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSACMHCP PEA 1 P29 sequence provides 423 support for the deduced sequence of this variant protein according to the present invention). Table 30 - Nucleic acid SNPs
As noted above, cluster HSACMHCP features 65 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 HSACMHCP_PEA_l_node_2 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): HSACMHCP PEA 1 T14. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_20 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 followmg transcnpt(s)- HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA 1 T7, HSACMHCP PEA 1 T17 and HSACMHCP PEA T26. Table 32 below descnbes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_22 according to the present invention is supported by 7 libranes. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T17 and HSACMHCP_PEA_1_T26. Table 33 below describes the starting and ending position of this segment on each transcnpt. Table 33 - Segment location on transcripts 425
Segment cluster HSACMHCP_PEA_l_node_25 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T17 and HSACMHCP_PEA_1_T26. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_43 according to the present invention is 42 6 supported by 8 libraries The number of libraries was determined as previously described This segment can be found in the following transcπpt(s): HSACMHCP PEA 1 T2, HSACMHCP PEA 1 T3, HSACMHCP PEA 1 T4, HSACMHCP PEAJ T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP PEA 1 T26 Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_45 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 transcπpt(s): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_ T7, HSACMHCP_PEA_1_T8 and HSACMHCP_PEA_1_T17. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts
427
Segment cluster HSACMHCP_PEA_l_node_46 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): HSACMHCP PEA 1 T17. Table 37 below descnbes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_48 according to the present invention is supported by 1 libraries. The number of libranes was detennined as previously described. This segment can be found in the following transcript(s): HSACMHCP PEA 1 T13. Table 38 below descnbes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_49 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This 428 segment can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP PEA T8, HSACMHCP PEA 1 T13 and HSACMHCP PEA 1 T26. Table 39 below describes the starting and ending position of this segment on each transcript.
Segment cluster HSACMHCP_PEA_l_node_57 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP_PEA_1_T26. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts
429
Segment cluster HSACMHCP_PEA_l_node_59 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_61 according to the present invention is 430 supported by 5 libraries. The number of libraπes was detennined as previously described. This segment can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSAC HCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA 1 T7, HSACMHCP PEA 1 T8, HSACMHCP PEA 1 T13 and HSACMHCP PEA 1 T26. Table 42 below describes the starting and ending position of this segment on each transcript. Table 42 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_63 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 43 below describes the starting and ending position of this segment on each transcript. 7 t/e 43 - Segment location on transcripts Y s & 431
Segment cluster HSACMHCP_PEA_l_node_65 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 44 below describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts
432 Segment cluster HSACMHCP_PEA_l_node_67 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSAC HCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 45 below describes the starting and ending position of this segment on each transcript. Table 45 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_71 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP_PEA_1_T26. Table 46 below describes the starting and ending position of this segment on each transcript. Table 46 - Segment location on transcripts 133
Segment cluster HSACMHCP_PEA_l_node_81 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): HSACMHCP_PEA_1_T3. Table 47 below describes the starting and ending position of this segment on each transcript. Table 47 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_87 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 48 below describes the starting and ending position of this segment on each transcript. Table 48 - Segment location on transcripts 434
Segment cluster HSACMHCP_PEA_l_node_89 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEA 1 T14 and HSACMHCP_PEA_1_T26. Table 49 below descnbes the starting and ending position of this segment on each transcript. Table 49 - Segment location on transcripts
135
Segment cluster HSACMHCP_PEA_l_node_96 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): HSACMHCP PEA 1 T2, HSACMHCP PEA 1 T3, HSACMHCP PEA 1 T4, HSACMHCP PEA 1 T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 aαl HSACMHCP_PEA_1_T26. Table 50 below describes the starting and ending position of this segment on each transcript. Table 50 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_97 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, 436 HSACMHCP_PEAJ_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEA 1 T14 and HSACMHCP_PEA_1_T26. Table 51 below describes the starting and ending position of this segment on each transcript. Table 51 - Segment location on transcripts
Segment cluster HSACMHCP PEA l node lOO 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 52 below describes the starting and ending position of this segment on each transcript. Table 52 - Segment location on transcripts
437
Segment cluster HSACMHCP_PEA_l_node_105 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): HSACMHCP_PEA_1_T7. Table 53 below describes the starting and ending position of this segment on each transcript. Table 53 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_106 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 54 below describes the starting and ending position of this segment on each transcript. Table 54 - Segment location on transcripts
438
Segment cluster HSACMHCP_PEA_l_node_107 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7 and HSACMHCP_PEA_1_T26. Table 55 below describes the starting and ending position of this segment on each transcript. Table 55 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_108 according to the present invention is supported by 7 libraries. The number of libranes was detennined as previously described. This segment can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T7 and HSACMHCP_PEA_1_T26. Table 56 below describes the starting and ending position of this segment on each transcript. 4 39 Table 56 - Segment location on transcripts
Segment cluster PISACMHCP PEA l node l l l 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 57 below describes the starting and ending position of this segment on each transcript. Table 57 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_113 according to the present invention is 440 supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA _T3, HSACMHCP_PEA_1_T4, HSACMHCP »EA_1_T6, HSACMHCPJPEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 58 below describes the starting and ending position of this segment on each transcript. Table 58 - Segment location on transcripts
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 HSACMHCP PEA l node O according to the present invention can be found in the following transcript(s): HSACMHCP_PEA_1_T8. Table 59 below describes the starting and ending position of this segment on each transcript. Table 59 - Segment location on transcripts 4 4 1 Transcnpt name Segment Segment starting position endmg position HSACMHCP_PEA_ _T8 1 21
Segment cluster HSACMHCP_PEA_l_node_3 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 transcπpt(s) HSACMHCP PEA 1 T14 Table 60 below describes the starting and ending position of this segment on each transcπpt Table 60 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_4 according to the present invention can be found in the following transcπpt(s) HSACMHCP PEA 1 T14 Table 61 below descnbes the starting and ending position of this segment on each transcript Table 61 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_16 according to the present invention is supported by 1 hbranes The number of libranes was detennined as previously descnbed. This segment can be found m the following transcπpt(s) HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA 1 TJ, HSACMHCP PEA_1_T17 and HSACMHCP PEA 1 T26 Table 442 62 below describes the starting and ending position of this segment on each transcript Table 62 - Segment location on transcripts
Segment cluster HSACMHCP PEA l node l 8 according to the present invention is supported by 3 libranes The number of libranes was detennined as previously descπbed This segment can be found in the following transcπpt(s)- HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T17 and HSACMHCP_PEA_1_T26. Table 63 below describes the starting and ending position of this segment on each transcript Table 63 - Segment location on transcripts
443
Segment cluster HSACMHCP_PEA_l_node_23 according to the present invention can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T17 and HSACMHCP_PEA_1_T26. Table 64 below describes the starting and ending position of this segment on each transcript. Table 64 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_27 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP PEA 1 T26. Table 65 below describes the starting and ending position of this segment on each transcript. Table 65 - Segment location on transcripts
444
Segment cluster HSACMHCP_PEA_l_node_29 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously descπbed. This segment can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA 1 T7, HSACMHCP PEA T8, HSACMHCP PEA 1 T17 and HSACMHCP PEA 1 T26. Table 66 below describes the starting and ending position of this segment on each transcript. Table 66 - Segment location on transcripts
4 4 5 Segment cluster HSACMHCP_PEA_l_node_31 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP PEA 1 T26. Table 67 below describes the starting and ending position of this segment on each transcript. Table 67 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_33 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_ T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP PEA 1 T26. Table 68 below describes the starting and ending position of this segment on each transcript. Table 68 - Segment location on transcripts 4 4 6
Segment cluster HSACMHCP_PEA_l_node_35 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA 1 T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP PEA 1 T26. Table 69 below describes the starting and ending position of this segment on each transcript. Table 69 - Segment location on transcripts
447
Segment cluster HSACMHCP_PEA_l_node_37 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP PEA 1 T8, HSACMHCP PEA 1 T17 and HSACMHCP PEA 1 T26. Table 70 below describes the starting and ending position of this segment on each transcript. Table 70 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_39 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP PEA 1 T26. Table 71 below describes the starting and ending position of this segment on each transcript. 448 Table 71 - Segment location on transcripts Transmptmame Segment Segmejit starting position ending position HSACMHCP PEA 1 T2 1080 1 196 HSACMHCP PEA 1 T3 1080 1 196 HSACMHCP PEA 1 T4 1080 196 HSACMHCP PEA 1 T6 1080 1196 HSACMHCP PEA 1 T7 1080 1196 HSACMHCP PEA 1 T8 522 638 HSACMHCP PEA 1 T17 1080 1196 HSACMHCP PEA 1 T26 1080 1196
Segment cluster HSACMHCP_PEA_l_node_40 according to the present invention can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP PEA T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T17 and HSACMHCP_PEA_1_T26. Table 72 below describes the starting and ending position of this segment on each transcript. Table 72 - Segment location on transcripts
4 4 9
Segment cluster HSACMHCP_PEA_l_node_51 according to the present invention is supported by 6 libraπes The number of libraries was determined as previously described. This segment can be found in the following transcπpt(s). HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 73 below describes the starting and ending position of this segment on each transcπpt. Table 73 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_53 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA _T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP_PEA_1_T26. Table 74 below describes the starting and ending position of this segment on each transcript. Table 74 - Segment location on transcripts 450
Segment cluster HSACMHCP_PEA_l_node_55 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 75 below describes the starting and ending position of this segment on each transcript. Table 75 - Segment location on transcripts
451
Segment cluster HSACMHCP_PEA_l_node_69 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA T7, HSACMHCP PEAJ T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 76 below describes the starting and ending position of this segment on each transcript. Table 76 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_72 according to the present invention can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP_PEA_1_T26. Table 77 below describes the starting and ending position of this segment on each transcript. Table 77 - Segment location on transcripts 452
Segment cluster HSACMHCP_PEA_l_node_73 according to the present invention is supported by 10 libraries The number of libraries was determined as previously descnbed This segment can be found in the followmg transcπpt(s) HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP_PEA_1_T26 Table 78 below descnbes the starting and ending position of this segment on each transcript Table 78 - Segment location on transcripts
453
Segment cluster HSACMHCP_PEA_l_node_74 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): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_ 1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13 and HSACMHCP PEA 1 T26. Table 79 below describes the starting and ending position of this segment on each transcript. Table 79 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_77 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 80 below describes the starting and ending position of this segment on each transcript. 454 Table 80 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_78 according to the present invention can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP PEA 1 T3, HSACMHCP PEA 1 T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP PEA 1 T26. Table 81 below describes the starting and ending position of this segment on each transcript. Table 81 - Segment location on transcripts
4 55
Segment cluster HSACMHCP_PEA_l_node_80 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEA 1 T14 and HSACMHCP PEA 1 T26. Table 82 below describes the starting and ending position of this segment on each transcript. Table 82 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_82 according to the present invention can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and 4 5 6 HSACMHCP PEA 1 T26. Table 83 below describes the starting and ending position of this segment on each transcript. Table 83 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_83 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEA 1 T14 and HSACMHCP_PEA_1_T26. Table 84 below describes the starting and ending position of this segment on each transcript. Table 84 - Segment location on transcripts
457
Segment cluster HSACMHCP_PEA_l_node_84 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEA 1 T14 and HSACMHCP_PEA_1_T26. Table 85 below describes the starting and ending position of this segment on each transcript. Table 85 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_85 according to the present invention is 4 58 supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSACMHCP PEA 1 T2, HSACMHCP PEA 1 T3, HSACMHCP_PEA_1_T4, HSACMHCP PEAJ T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEAJ T14 and HSACMHCP_PEA_1_T26. Table 86 below describes the starting and ending position of this segment on each transcript. Table 86 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_90 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): HSACMHCP PEA 1 T4. Table 87 below describes the starting and ending position of this segment on each transcript. Table 87 - Segment location on transcripts
4 59
Segment cluster HSACMHCP_PEA_l_node_91 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): HSACMHCP_PEA_1_T2, HSACMHCP PEAJ T3, HSACMHCP_PEA_1_T4, HSACMHCP PEAJ T6, HSACMHCP PEAJ T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP PEAJ T14 and HSACMHCP_PEA_1_T26. Table 88 below describes the starting and ending position of this segment on each transcript. Table 88 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_92 according to the present invention can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 89 below describes the starting and ending position of this segment on each transcript. Table 89 - Segment location on transcripts 460
Segment cluster HSACMHCP_PEA_l_node_93 according to the present invention is supported by 14 libraries. The number of libraries was determined as previously descπbed. This segment can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP PEA 1 T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 90 below describes the starting and ending position of this segment on each transcript. Table 90 - Segment location on transcripts
4 61
Segment cluster HSACMHCP_PEA_l_node_95 according to the present invention can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP PEA 1 T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA _T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 91 below describes the starting and ending position of this segment on each transcript. Table 91 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_98 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA 1 T13, 4 62 HSACMHCP PEAJ T14 and HSACMHCP_PEA_1_T26 Table 92 below describes the starting and ending position of this segment on each transcript Table 92 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_103 accordmg 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 transcπpt(s) HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP PEA 1 T26 Table 93 below descnbes the starting and ending position of this segment on each transcnpt Table 93 - Segment location on transcripts
4 63
Segment cluster HSACMHCP_PEA_l_node_104 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): HSACMHCP PEA 1 T2, HSACMHCP_PEA_1_T3, HSACMHCP_PEA_1_T4, HSACMHCP_PEA_1_T6, HSACMHCP_PEA_1_T7, HSACMHCP_PEA_1_T8, HSACMHCP_PEA_1_T13, HSACMHCP_PEA_1_T14 and HSACMHCP_PEA_1_T26. Table 94 below describes the starting and ending position of this segment on each transcript. Table 94 - Segment location on transcripts
Segment cluster HSACMHCP_PEA_l_node_109 according to the present invention is 464 supported by 18 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HSACMHCP_PEA_1_T2, HSACMHCP_PEA_1_T3, HSACMHCP PEAJ T4, HSACMHCP_PEA_1_T6, HSACMHCP PEA T7, HSACMHCP PEA 1 T8, HSACMHCP PEA 1 T13, HSACMHCP PEA TI4 and HSACMHCP PEA 1 T26. Table 95 below describes the starting and ending position of this segment on each transcript. Table 95 - Segment location on transcripts
Variant protein alignment to the previously known protein: Sequence name: MYH6_HUMAN_V1
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P2 x MYH6_HUMAN_V1
Alignment segment 1/1:
Quality: 17978.00 Escore: 0 Matching length: 1855 Total length: 1855 465 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I II I I I I I 1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50
51 I SREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 I I I I I I I I I I I I I I II I I I I I II I I I I I I I I I I I I I I I I I I I II I I I I I I 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 101 VLFNLKERYAA MIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150 I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I 101 V FNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150
151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200
201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250 I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
251 IHFGATGKLASADIETYLLEKSRVIFQ KAERNYHIFYQI SNKKPELLD 300 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I 251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300 . . . . . 301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I 301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 351 YKLTGAIMHYGNMKF QKQREEQAEPDGTEDADKSAYLMG NSADLLKGL 400 I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II 351 YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAY MGLNSADLLKGL 400 466 401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450 I I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I I I I I I I I I I I I I I I I I 401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINAT ET 450
451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I II 451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500
501 EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550 I I I I I I I I I I I I I I I II I I I I I I I I I I I I II I II I I I I II I I I I I I I I II
501 EYKKEGIE TFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550
551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600 I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I II I 551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600
601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650 II I I I I I II I I I I I I I I I I I I I II I I I I I I I I I II I I I I I I I I I I I I I I I
601 PLNETVVALYQKSSLKLMATLFSSYATADTGDΞGKSKGGKKKGSSFQTVS 650 . . . . .
651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700 I I I I I II I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I 651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700
701 LEGIRICRKGFPNRILYGDFRQRYRI NPVAIPEGQFIDSRKGTEKLLSS 750 I I II I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I 701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750
751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800 I I I I I I M I I II II I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I
751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800
801 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I II I II 801 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850
851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900 I I I II I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I 467 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900
901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRK EDECS 950 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 901 NDAEERCDQLIKNKIQLEAKVKEMNER EDEEEMNAELTAKKRKLEDECS 950
951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000 I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000
1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I
1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGS EQEKKVRMDL 1050
1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100
1101 A ALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSD SRELEEISE 1150 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I II I I I I I I I I I I I I I II
1101 ALALQLQKK KENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150
1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200
1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250 I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250 . . . . .
1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300 I II I I I I II I I I II I I I I I I I I I I I I II I I I I I I I I I I I II I II I I I I I I 1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEA I 1300
1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350 I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I I I II 1301 SQLTRGKLSYTQQMED KRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350 468 1351 EETEAKAELQRV SKANSEVAQWRTKYETDAIQRTEELEEAKKK AQRLQ 1400 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I II I I I I II I I I I I I I I I I I I 1351 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1400
1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1450 I I I I I II I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIED MVDVERSNAAAAALDKKQRN 1450
1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I II I I II I
1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500
1501 KRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAE 1550 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I 1501 KRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEK ELQSALEEAE 1550
1551 ASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQ 1600 I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I 1551 ASLEHEEGKILRAQ EFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQ 1600 . . . . .
1601 TS DAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQS 1650 I I I I I I I I I I I I II II I I I I I II I I I II I I I I I I I I I I I I I I I I I I I I I I 1601 TSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKS QS 1650
1651 LLKDTQIQ DDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERS 1700 I I I I I I II I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I 1651 LKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERS 1700
1701 RKLAEQELIETSERVQLLHSQNTS INQKKKMESDLTQLQSEVEEAVQEC 1750 I I I || I I I I I I I I I I I I I I I I I I I II I II I I I II I I I I I I I I I I I I I II I
1701 RK AEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC 1750
1751 RNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLD 1800 I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1751 RNAEEKAKKAITDAAMMAEELKKEQDTSAH ERMKKNMEQTIKDLQHRLD 1800
1801 EAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIK 1850 I I I I I I I I I I I I I I I I I I I I I I I I II II I I I II II I I I I I II I I I I I I I I 469 1801 EAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIK 1850
1851 ELTYQ 1855 lll ll 1851 ELTYQ 1855
Sequence name: MYH6_HUMAN_V2
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P3 x MYH6_HUMAN_V2
Alignment segment 1/1: Quality: 12901.00 Escore: 0 Matching length: 1328 Total length: 1328 Matching Percent Similarity: 99.92 Matching Percent Identity: 99.85 Total Percent Similarity: 99.92 Total Percent Identity: 99.85 Gaps : 0
Alignment :
1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50
51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 . . . . . 101 VLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150 I I I I I II I I I I I I I I I I I I I I I I I I I I II I I I II I I II I I I I I I I I I I I I 101 VLFNLKERYAA MIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150 151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I II 151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 470 201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I 201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300
301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 II II II I I I I II I II I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I
301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350
351 YKLTGAIMHYGNMKFKQ QREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400 I II I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 351 YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400
401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450 I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I 401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFN MVTRINATLET 450 . . . . .
451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 451 KQPRQYFIGVLDIAGFEIFDFNΞFEQLCINFTNEKLQQFFNHHMFVLEQE 500
501 EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 501 EYKKEGIE TFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550
551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILG LEKNKD 600 I M I I I I I I I I I I I I I I II I I I I I I I I I I II I I I I I I I I I I I I I I I I II I
551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600
601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650 I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I 601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650
651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700 I I I I I I I I I I I I I I I I I I II I I I I I II I I I I I I I I I I I I I I I I I I I I I I I 471 651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700
701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I II I I I II I I I I I I I I I I I I I 701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750
751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800 I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I I 751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQ MR 800
801 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I II I I I I I I 801 IEFKKIVERRDALLVIQWNIRAFMGVKN PWMKLYFKIKPLLKSAETEKE 850 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900
901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950 I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950
951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I i E I I I I I I I I I I I I I I I I I I 951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000
1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050 I I I I I I I I II I I I II I I I I I I II I I I I I I I I I I I I II I I I I I I I I II I I I 1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050 . . . . .
1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100 I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I II I I II I I I I I I I I 1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100
1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150 I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150 472 1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200 I I I I I I II I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I 1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200 1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250 I I I I I I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I II I I I I 1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250
1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300 I I I II I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300
1301 SQLTRGKLSYTQQMEDLKRQLEEEGKVR 1328 II I I I I I I I I I I I I I I I I I II I I I I I : 1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAK 1328
Sequence name: MYH6_HUMAN_V2
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P4 x MYH6_HUMAN_V2
Alignment segment 1/1: Quality: 14661.00 Escore: Matching length: 1508 Total length: 1508 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50
51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I II I I I I I I I I I I I I I 473 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100
VLFNLKERYAAWMIYTYSGLFCVTVNPYK LPVYNAEVVAAYRGKKRSEA 150
I I I II I I I I I I I I I I I I I I I I I I I I I II I I I II I I I I I I I I I I II I I II I VLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150
PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200
I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200
IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
I I I I I I I I I I II I I I II I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300
I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300
MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I M I I I I I I I I I I I I I I I I I I I MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350
YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400
CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450
I I I II I I I I I I I I I I I I II I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450 . . . . . KQPRQYFIGVLDIAGFEIFDFNΞFEQLCINFTNEKLQQFFNHHMFVLEQE 500
I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500
EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550 I I I I I I I I I II I I I I I I I I I II I I I I I I I I I I I I I I II I I I I I I I I I I I I EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550 474 551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II 551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600 601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650 I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I II I I I I I I I I I I 601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650
651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700 I I I I I I I I II I I I I I I I I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I 651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700
701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750 I I I I I I I I I I I I I I I II I I I I I I I I II I I I I I I I I I I I I I I I I I I I II I I 701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750
751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800 I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800 . . . . . 801 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850 I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I 801 IEFKKIVERRDALLVIQ NIRAFMGVKNWP MKLYFKIKPLLKSAETEKE 850 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900 I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900
901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950
901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950
951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000 I I I I I I I I I I II I I I II I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I 951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000
1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050 I I I I I I I I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I II I 475 1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050
1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100 I I I I II I I I I I I I I I I I II I I I II I I I I I I I I I I I I I II I I I I I I I II II
1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100
1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I E I I I I I I I I I I I I I I I I I I
1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150
1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200 I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200
1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250
1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300 I I I I I I I I I I I I M I I M I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I
1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300
1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350 I I I I I I I I I I I I I I I II I I I II I I I I I I II I I I I I I I I I I I I I I I I I I I I 1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350
1351 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1400 I I I I I I I I I I I I I I I I II I I I I I I I I II I I I I I I I II I I I I I I I I I I I I I 1351 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1400 . . . . .
1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1450 I I I I I I I I I I I I I II I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I 1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1450
1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500 I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I II I I I I I I 1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500 476 1501 KRENKNLQ 150 I I I I I I I I 1501 KRENKNLQ 1505
Sequence name: MYH6_HUMAN_V1
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P6 x MYH6_HUMAN_V1
Alignment segment 1/1:
Quality: 17088.00 Escore: Matching length: 1763 Total length: 1763 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100
101 VLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150 I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 101 VLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150
151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200
201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250 I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I I I I II I I I I I I I I I I I I 477 201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300 I I I I II II I I I I I I I I I I I I I I I I I I II I I I II I I I II I I I I II I I I I II 251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300
301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350
351 YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 351 YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400
401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450 I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I 401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450
451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I II I I I I I I II I I II I I I I
451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500
501 EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550 I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I II I I I I I II I I I 501 EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550
551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600 I I I I I I I I II I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I 551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILG LEKNKD 600 . . . . .
601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650
651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700 I I I I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700 478 701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750 I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I II I I I I I I I I I I I I I I I I 701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750 751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800
801 IEFKKIVERRDALLVIQ NIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850 I I I I I I I I II I I I I I II I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 801 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850
851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900 I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900
901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950 I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I 901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950 . . . . . 951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000 I I I I I I I I I I I I I I I I II I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000
1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050
1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100 M I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100
1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150 I I I I I I I II I I II I I I I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I I 1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150
1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I 479 1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200
1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250 I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I II I I 1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250
1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300
1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350
1351 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1400 I I I I I I I I I I I I I I I I I I I I I I I II I I I I II I I I I I I I I I I I I I I I I I I I
1351 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1400
1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1450 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I II I I I I I I I I I II I I I I I I
1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1450
1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500
1501 KRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAE 1550 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I I I 1 1501 KRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAE 1550 . . . . .
1551 ASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQ 1600 I I I II I I I I I II I I I II I I I I I I I II I I I I I I I I I I I I I I II I II I I I I I 1551 ASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQ 1600
1601 TSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQS 1650 I I I I I II I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I 1601 TSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQS 1650 480 1 651 LLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERS 1 700 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1651 LLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERS 1700 1701 RKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC 1750 I I I I I I I II I II I I I II I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I 1701 RKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC 1750
1751 RNAEEKAKKAITD 1763 I I I I I I I I I I I I I 1751 RNAEEKAKKAITD 1763
Sequence name: MYH6_HUMAN_V3
Sequence documentation:
Alignment of: HSACMHCP_PEA__1_P12 x MYH6_HUMAN_V3
Alignment segment 1/1:
Quality: 13633.00 Escore: 0 Matching length: 1413 Total length: 1413 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.93 Total Percent Similarity: 100.00 Total Percent Identity: 99.93 Gaps: 0
Alignment :
22 QPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEA 71 : I I I I I I I I I I I M I I I I I I I I I I I I I I I I I I II I I II I I I I I I I I I I I I 527 KPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEA 576
72 HFSLIHYAGTVDYNILG LEKNKDPLNETVVALYQKSSLKLMATLFSSYA 121 I II I I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I II 577 HFSLIHYAGTVDYNILG LEKNKDPLNETVVALYQKSSLKLMATLFSSYA 626
122 TADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCII 171 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 481 627 TADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCII 676
172 PNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRI 221 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 677 PNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRI 726
222 LNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAGLLGLLE 271 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 727 LNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAGLLGLLE 776
272 EMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGV 321 I I I I I I I I I I I I I I II I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I II I 777 EMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQ NIRAFMGV 826 322 KNWP MKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELE 371 I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 827 KNWP MKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELE 876
372 EKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNE 421 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 877 EKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNE 926
422 RLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENK 471 I I I I II I I I I II I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I 927 RLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENK 976
472 VKNLTEEMAGLDEIIAKLTKEKKALQEAHQQALDDLQVEEDKVNSLSKSK 521 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I II 977 VKNLTEEMAGLDEIIAKLTKEKKALQEAHQQALDDLQVEEDKVNSLSKSK 1026 . . . . . 522 VKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKL 571 I I I I I II I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I II I I I I I I I I I
1027 VKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKL 1076 572 QLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEA 621 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I II I I I I I I I 1077 QLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEA 1126 482 622 ERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKM 671 I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I 1127 ERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKM 1176 672 RRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF 721 I I I I I I I I II I I I I I I I I I I I II II I I I I II I I I I I I I I I I I I I I I I I I I
1177 RRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEF 1226
722 KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFT 771 I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1227 KLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFT 1276
772 TQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGK 821 I I I I I I I I I I I I I I II I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I 1277 TQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGK 1326
822 AKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTK 871 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1327 AKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTK 1376 . . . . . 872 YETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNE 921 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1377 YETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNE 1426 922 IEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEESQSELESSQKEA 971 I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1427 IEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEESQSELESSQKEA 1476
972 RSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVH 1021 I I M I I I I I I M I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I
1477 RSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVH 1526
1022 ELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIER 1071 I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 1527 ELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIER 1576
1072 KLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNE 1121 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I 4 83 1577 KLAEKDEEMEQAKRNHQRWDSLQTSLDAETRSRNEVLRVKKKMEGDLNE 1 626
1122 MEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIV 1 17 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I 1627 MEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIV 1676 1172 ERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLI 1221 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I II I I I 1677 ERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLI 1726 . . . . . 1222 NQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEELKKEQD 1271 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1727 NQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEELKKEQD 1776 1272 TSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEG 1321 I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I II II I I I I I I I II I 1777 TSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEG 1826
1322 ELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLLRLQDLVDKLQLK 1371 I II I I I I I I II I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I 1827 ELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLLRLQDLVDKLQLK 1876
1372 VKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKLRAKS 1421 I I I I I I I I I I I I II I I I I I I I I II I I I I I I I I I I I II I I I I I I II I I I I I 1877 VKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKLRAKS 1926
1422 RDIGAKQKMHDEE 1434 I I I I I I I I I I I I I 1927 RDIGAKQKMHDEE 1939
Sequence name: MYH6_HUMAN_V2
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P16 x MYH6_HUMAN_V2
Alignment segment 1/1: 484 Quality: 5155.00 Escore: 0 Matching length: 527 Total length: 527 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment :
1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 I I I I I I I I I I I I I I I I II I I I II I I I I I I I I II I I I I I I I I I I I I I I I I I 1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50
51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100
101 VLFNLKERYAAWMIYTYSGLFCVTVNPYK LPVYNAEVVAAYRGKKRSEA 150 I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I II I I I I I I I I I I 101 VLFNLKERYAA MIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150 . . . . . 151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I 151 PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250 I I I I I I I II I II I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II 201 IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I M I I I I I I 251 IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300
301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 I I I I I I I II I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I II I I I 301 MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350
351 YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400 I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 485 351 YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400
401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I 401 CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFN MVTRINATLET 450
451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I 451 KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500
501 EYKKEGIE TFIDFGMDLQACIDLIEK 527 I I I I I II I I I I I I I I I II I I I I I I I I I 501 EYKKEGIEWTFIDFGMDLQACIDLIEK 527
Sequence name: MYH6_HUMAN_V1
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P25 x MYH6_HUMAN_V1
Alignment segment 1/1:
Quality: 17293.00 Escore: 0 Matching length: 1798 Total length: 1855 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 96.93 Total Percent Identity: 96.93 Gaps: 1
Alignment :
1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 I I I I I I I I I I I I I I I I I I I I I I I II I I I I II I I I II I I II I I I I I I I I I I 1 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAK 50 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 51 ILSREGGKVIAETENGKTVTVKEDQVLQQNPPKFDKIEDMAMLTFLHEPA 100 48 6 VLFNLKERYAAWMI YTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 1 50
I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I VLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEA 150
PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200 I I I I I I I I II I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I PPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAA 200
IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250 I I II I I I I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I I I I I I I I I I I IGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIR 250
IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300 I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I IHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLD 300
MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350
I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I MLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGV 350 . . . . . YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400
I I I I I I I I I I I I I I II I I I II I I I II I I I I I I I I I I I II I I I I I I I I I I I YKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGL 400
CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450 I I I II I I I I I I I I I I I I I I I I I I I I I I I I I II I II I I I I I I I I II I I I I I CHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLET 450
KQPRQYFIGVLDIAGFEIFD 470 I I I I I II I I II II I I I I I II KQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQE 500 PMGIMSILEEECMFPKATDMTFK 493 I I I I I I I II I I I I I I I I I II I II EYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFK 550
AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 543 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I II I I I I I I I 487 551 AKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKD 600
544 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 593 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 601 PLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVS 650
594 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 643 I I I I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I I I I I I I I I I I I I I I 651 ALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGV 700
644 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 693 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I II I 701 LEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS 750 694 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 743 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I 751 LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMR 800
744 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 793 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 801 IEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKE 850
794 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 843 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 851 MATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNL 900
844 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 893 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I 901 NDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECS 950 . . . . . 894 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 943 I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 951 ELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKA 1000 944 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 993 II I II I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I II I I 1001 LQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDL 1050 488 994 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1043 II I I I I I II I I I I I I II I I I I I I I II I I I I I I I M I I I I I I I I I I I I I I I 1051 ERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQ 1100
1044 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1093 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I 1101 ALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE 1150
1094 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1143 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1151 RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHAD 1200
1144 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1193 I I II I I I I I I I I I I I I I II I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I 1201 SVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKV 1250
1194 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1243 I I II I I I I II I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1251 SRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALI 1300 . . . . .
1244 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1293 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1301 SQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYE 1350
1294 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1343 I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I II I I 1351 EETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQ 1400
1344 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1393 I I I II I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I II I I I I I I I I I I I
1401 DAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRN 1450
1394 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1443 I I I I I I I I I I I I II I I I II I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I 1451 FDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETF 1500
1444 KRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAE 1493 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I II 489 1501 KRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAE 1550
1494 AΞLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQ 1543 I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1551 ASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQ 1600
1544 TSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQS 1593 I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1601 TSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQS 1650
1594 LLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERS 1643 I I I I I I I I II I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1651 LLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERS 1700 1644 RKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC 1693 I I I I I I I I I I I I I I I I I I I I I I I I II I I I I II I I I I I I II I I I I I I I I I I 1701 RKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQEC 1750
1694 RNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLD 1743 I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I 1751 RNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLD 1800
1744 EAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIK 1793 I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I II I I I I I I I I I I I I I I I I 1801 EAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIK 1850
1794 ELTYQ 1798 lllll 1851 ELTYQ 1855
Sequence name: MYH6_HUMAN_V3
Sequence documentation:
Alignment of: HSACMHCP_PEA_1_P28 x MYH6_HUMAN_V3
Alignment segment 1/1: 490 Quality: 17163.00 Escore: 0 Matching length: 1775 Total length: 1775 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps : 0
Alignment :
1 MLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANK 50 I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I 165 MLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANK 214
51 GTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIRIHFGATGKLASADI 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I II I I I I I 215 GTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIRIHFGATGKLASADI 264
101 ETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNPYDYAFV 150 I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I 265 ETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNPYDYAFV 314 . . . . . 151 SQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMK 200 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 315 SQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMK 364 201 FKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVGNEYVTK 250 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I 365 FKQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVGNEYVTK 414
251 GQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLDIA 300 I I I I I I I I I M I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 415 GQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPR QYFIGVLDIA 464
301 GFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDF 350 I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 465 GFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDF 514
351 GMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNF 400 I I I I I I I I I I I I I I I II I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 491 515 GMDLQACIDLIEKPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNF 564
401 QKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSS 450 I I I I I I I I I I I I I I I I I I I I I I M I I I I I I I I I I I I II I I I I I I I I I I I I
565 QKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSS 614
451 LKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNL 500 I I I I II I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I
615 LKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNL 664
501 RTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNR 550 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
665 RTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNR 714
551 ILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTK 600 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I 715 ILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTK 764
601 VFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALL 650 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I
765 VFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALL 814
651 VIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKET 700 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 815 VIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKET 864
701 LEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNK 750 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I 865 LEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNK 914 . . . . .
751 IQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLA 800 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 915 IQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLA 964
801 KVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKALQEAHQQALDDLQV 850 I I I I I I I I I I I I I I I I I I I I I I I I I I I II II I I I I I I I I I I I I I I I II I I 965 KVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKALQEAHQQALDDLQV 1014 492 851 EEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLT 900 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II 1015 EEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLT 1064 901 QESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQ 950 I I I II I I I I I I I I I I II I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1065 QESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQ 1114
951 ARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIE 1000 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1115 ARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIE 1164
1001 MNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQR 1050 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I 1165 MNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQR 1214
1051 VKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVK 1100 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I II I I 1215 VKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVK 1264 . . . . .
1101 LEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQM 1150 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I 1265 LEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQM 1314
1151 EDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLS 1200 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I 1315 EDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLS 1364
1201 KANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCS 1250 I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1365 KANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCS 1414
1251 SLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAE KQKYEE 1300 I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I II I I I I II I I I I I I II I 1415 SLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEE 1464
1301 SQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDL 1350 II I II I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I II I I I I I I I 493 1465 SQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDL 1514
1351 TEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQ 1400 I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I II I I II I I I I I I I I I 1515 TEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQ 1564
1401 LEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVL 1450 I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I II I I I I I I I I I I I I 1565 LEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVL 1614
1451 RVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVR 1500 I I I II I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1615 RVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVR 1664
1501 ANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSER 1550 II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I
1665 ANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSER 1714
1551 VQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDA 1600 I I I I I I I I I I I I I I 11 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1715 VQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDA 1764
1601 AMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQL 1650 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1765 AMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQL 1814
1651 QKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLL 1700 I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II II 1815 QKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLL 1864 . . . . .
1701 RLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADI 1750 I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1865 RLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADI 1914
1751 AESQVNKLRAKSRDIGAKQKMHDEE 1775 I I I I I I I I I I I I I I I I I I I I I I I I I 1915 AESQVNKLRAKSRDIGAKQKMHDEE 1939 494
Sequence name: MYH6 HUMAN V3
Sequence documentation:
Alignment of: HSACMHCP PEA 1_P29 x MYH6_HUMAN_V3
Alignment segment 1/1:
Quality: 7441.00 Escore 0 Matching length: 775 Total length 775 Matching Percent Similarity: 100.00 Matching Percent Identity 100.00 Total Percent Similarity: 100.00 Total Percent Identity 100.00 Gaps: 0
Alignment:
1 MNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQR 50 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I II I I I I I 1165 MNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQR 1214
51 VKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVK 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I 1215 VKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVK 1264 101 LEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQM 150 I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I 1265 LEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQM 1314
151 EDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLS 200
1315 EDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLS 1364
201 KANSEVAQ RTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCS 250 I I I I I I I I I I II I I I I I I I II I I I I I I I I I I I I I I I I I I I I II I I I I I I I 1365 KANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCS 1414
251 SLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEE 300 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I 495 1415 SLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEE 1464
301 SQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDL 350 I I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1465 SQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDL 1514
351 TEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQ 400 I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1515 TEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQ 1564
401 LEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVL 450 I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1565 LEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVL 1614 451 RVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVR 500 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1615 RVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVR 1664
501 ANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSER 550 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I ! I I I I I
1665 ANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSER 1714
551 VQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDA 600 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1715 VQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDA 1764
601 AMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQL 650 I II I II I I I II I I I I I I I I II I I I I I I I I I I I I I I I I I I I I I I I I I II I I 1765 AMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQL 1814 . . . . . 651 QKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLL 700 I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I
1815 QKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLL 1864 701 RLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADI 750 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1865 RLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADI 1914 496 751 AESQVNKLRAKSRDIGAKQKMHDEE 775 I I I I I I I I I I I I I I I I I I I I I I I I I 1 915 AESQVNKLRAKSRDIGAKQKMHDEE 1 939
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 incoφorated 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 incoφorated 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.
4 97 < 1 60> NUMBER OF SEQ I D NOS : 350
<210> SEQ I D NO 1
<211> Length: 2,110
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 1
>S67314_PEA_1_T4
TCTGCAGGAGGGGAGCTGGGAACGACCTGAGCTAAAGCTCGGAGCTGTGCGAAGAAACCGGAAAAGCCCAGAGCACT
TGCAGGGGCGGGTGGGGAGCTAGATGGTGGGGTGGGGTGGGGACGGAGGAGGGCCAGCAGGAGACATTCCGCAGGGA
GGGGCAAGCACGTGTGAGGCGGGCGGGGCGCGAAGGGTCAGGCTTTTGCTCAAAACAGGCAGAGGACAAGGTCAGCT
CAGCCGCAGACCGAGCCGCTGGTGACTGTCTCCGCCACCAGGCAGTGAGAGTGAAGGGAGAGCGCGAGCTCTGAAGC
CCGCTAGACTAAGCTTGSAATCTGAGCTCCATTCACCCCCTCCTATTTCTTGAGACCTTGTCAGTTCCCCTGTGAGC
CTCGGACTCCTCACTTGTAAAACGAGGACAGATGCCCGTGCCAGAAGTCAACCAGAGCTTTCCCCGGCGTGGGCACC
AGCCCAAGGGCGTTTTGCTTTTCTAGTCTCATCTCTGCTCTGACGCTAAGCTCAAAGAGGGACTGGGGGACGGGAAG
ATATCCACCATGGCATGCGCCCTAGCTCTCGGGCTGGTGTTGGCTGCTTCCTTCTCAGATTCCAGAGTGCCTAGAGG
CCAGGAAAGGGAGAAGGTCCTACCAGCCTGGGGTAGGGACTCGGGGGCCAGGCACTGGCGCTGACGCAGGCTAGCAG
GGCGCCACTGGCTGGTCCCCACCCACCTCGGTGGGTTGGGGGATGGGCGCACCAGCCCCTCCTGGGTGAGCCCTAGC
CTGGGGCTTCCTATTTCGGGAGCCGGGGGCGTGGGCCACGTCTCCTCATGTGATGCGAGGGCTATTTAAAGCGGCAG
CCCGGGCAGGGAGCCGCCGTCGGAGCCCTTGCACGCCTGCTCTCTTGTAGCTTCTCTCAGCCTAGCCCAGCATCACT
ATGGTGGACGCTTTCCTGGGCACCTGGAAGCTAGTGGACAGCAAGAATTTCGATGACTACATGAAGTCACTCGGTGT
GGGTTTTGCTACCAGGCAGGTGGCCAGCATGACCAAGCCTACCACAATCATCGAAAAGAATGGGGACATTCTCACCC
TAAAAACACACAGCACCTTCAAGAACACAGAGATCAGCTTTAAGTTGGGGGTGGAGTTCGATGAGACAACAGCAGAT
GACAGGAAGGTCAAGTCCATTGTGACACTGGATGGAGGGAAACTTGTTCACCTGCAGAAATGGGACGGGCAAGAGAC
CACACTTGTGCGGGAGCTAATTGATGGAAAACTCATCCTGGTAAGATGGGCAACTTTGGAGCTATATCTGATTGGTT
ATTACTACTGCTCTTTCAGCCAAGCCTGTTCTAAAAAGCCAAGTCCTCCCCTGAGAGCTGTAGAAGCTGGGACAAGA
GAGTGGTTGTGGGTCAGGGTGGTATCAGGTGGGAATTTTCTGTGTAGTGGCTTTGGACTCACACAGGCCGGAACTCA
AATCTTACCTTATAGGCTACATGACTGTGGGCAAATCACCTTTTCCAAGTGCAACTGTAAAACGGGTATTAATAATA
CCAACCTTGTAGGGCTGCTGGGAAGCCTGTAAGAGACAGTGTATGCACAGCACAAAGCATCACTGATTGAGGAACAC
AGCAGGTGCTCCATGTCCTTTGTTTGCTCTTCCTGTGTTTCTACCTTGCCTCACCTCAGGAAGAAGTAGAAAACAGG
GCCAAATCTGATCCCAGGCCCTCTAGGAGGGGCTCCCATTGCCTATCTCAGCATTCCCTTTCCTCTCCTCCCTAGGA
CTGCATTGTCACTTGCAGGGACAGGCTCGTGACTGGTGGGGACACTGAATGACAGTACAGTCCTTTCTTCCCCATTC
TAGTCCTACCCCATTTTCATGCTTTCTATGTCTGGCCTACTGAAACTACTTGACTACTGCTTGGGTAGGAAGTACCA
CAGCCAGGCTGGCAGATCTGTTCAAGCTTGGGGACTTCACTTGGAGAATCTAGCCTTGACTGAATTCCCCCCAGACC
CAGGGAGAGCAGCCAACTGTGGATTCTGCCTAACCACAGGGCCTCAGGTTTTCACCTAGGCATCTTCACTGCACACC
TTCTTGGGTCAGCATAACCTGTTAACTGCAT 498
<210> SEQ ID NO 2
<211> Length: 1,733
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 2
>S67314_PEA_1_T5
TCTGCAGGAGGGGAGCTGGGAACGACCTGAGCTAAAGCTCGGAGCTGTGCGAAGAAACCGGAAAAGCCCAGAGCACT
TGCAGGGGCGGGTGGGGAGCTAGATGGTGGGGTGGGGTGGGGACGGAGGAGGGCCAGCAGGAGACATTCCGCAGGGA
GGGGCAAGCACGTGTGAGGCGGGCGGGGCGCGAAGGGTCAGGCTTTTGCTCAAAACAGGCAGAGGACAAGGTCAGCT
CAGCCGCAGACCGAGCCGCTGGTGACTGTCTCCGCCACCAGGCAGTGAGAGTGAAGGGAGAGCGCGAGCTCTGAAGC
CCGCTAGACTAAGCTTGCAATCTGAGCTCCATTCACCCCCTCCTATTTCTTGAGACCTTGTCAGTTCCCCTGTGAGC
CTCGGACTCCTCACTTGTAAAACGAGGACAGATGCCCGTGCCAGAAGTCAACCAGAGCTTTCCCCGGCGTGGGCACC
AGCCCAAGGGCGTTTTGCTTTTCTAGTCTCATCTCTGCTCTGACGCTAAGCTCAAAGAGGGACTGGGGGACGGGAAG
ATATCCACCATGGCATGCGCCCTAGCTCTCGGGCTGGTGTTGGCTGCTTCCTTCTCAGATTCCAGAGTGCCTAGAGG
CCAGGAAAGGGAGAAGGTCCTACCAGCCTGGGGTAGGGACTCGGGGGCCAGGCACTGGCGCTGACGCAGGCTAGCAG
GGCGCCACTGGCTGGTCCCCACCCACCTCGGTGGGTTGGGGGATGGGCGCACCAGCCCCTCCTGGGTGAGCCCTAGC
CTGGGGCTTCCTATTTCGGGAGCCGGGGGCGTGGGCCACGTCTCCTCATGTGATGCGAGGGCTATTTAAAGCGGCAG
CCCGGGCAGGGAGCCGCCGTCGGAGCCCTTGCACGCCTGCTCTCTTGTAGCTTCTCTCAGCCTAGCCCAGCATCACT
ATGGTGGACGCTTTCCTGGGCACCTGGAAGCTAGTGGACAGCAAGAATTTCGATGACTACATGAAGTCACTCGGTGT
GGGTTTTGCTACCAGGCAGGTGGCCAGCATGACCAAGCCTACCACAATCATCGAAAAGAATGGGGACATTCTCACCC
TAAAAACACACAGCACCTTCAAGAACACAGAGATCAGCTTTAAGTTGGGGGTGGAGTTCGATGAGACAACAGCAGAT
GACAGGAAGGTCAAGTCCATTGTGACACTGGATGGAGGGAAACTTGTTCACCTGCAGAAATGGGACGGGCAAGAGAC
CACACTTGTGCGGGAGCTAATTGATGGAAAACTCATCCTGGATGTTCTGACAGCCTGGCCAAGCATCTACAGGAGAC
AAGTCAAAGTTTTAAGAGAAGATGAAATAACAATTCTTCCTTGGCATCTCCAATGGAGTAGAGAGAAGGCAACAAAG
CTTCTCAGACCCACATTACCGAGCTATAACAACCATGGCTGGGAGGAGCTGAGAGTTGGCAAATCAATAGTTTAGCT
ATGTTGCTGAACCTTCCTGGATGGCAAGACCATGGAAGTCCATCACAAGATATTATGGGGTCAGGAGCCTCACTGGG
TTCTGCCCCTTATATAGGTGAATATCCTGGGAAAGTAAAAATGAAAATACAGAGTCTGGCACCAGTTCCCTGCAAGC
CTGGTCCAGCCTGGATAAAGAAGTGAGGAGAGTAATAATACTGCCTTACACCTAAACAGTGCTTTAGTTTATCAAGC
TTTTTGCATCCTTATCTTACAATAATAGTCTGTAGAGTC
<210> SEQ ID NO 3
<211> Length: 1,822
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 3 499 >S67314_PEA_1_T6
TCTGCAGGAGGGGAGCTGGGAACGACCTGAGCTAAAGCTCGGAGCTGTGCGAAGAAACCGGAAAAGCCCAGAGCACT
TGCAGGGGCGGGTGGGGAGCTAGATGGTGGGGTGGGGTGGGGACGGAGGAGGGCCAGCAGGAGACATTCCGCAGGGA
GGGGCAAGCACGTGTGAGGCGGGCGGGGCGCGAAGGGTCAGGCTTTTGCTCAAAACAGGCAGAGGACAAGGTCAGCT
CAGCCGCAGACCGAGCCGCTGGTGACTGTCTCCGCCACCAGGCAGTGAGAGTGAAGGGAGAGCGCGAGCTCTGAAGC
CCGCTAGACTAAGCTTGCAATCTGAGCTCCATTCACCCCCTCCTATTTCTTGAGACCTTGTCAGTTCCCCTGTGAGC
CTCGGACTCCTCACTTGTAAAACGAGGACAGATGCCCGTGCCAGAAGTCAACCAGAGCTTTCCCCGGCGTGGGCACC
AGCCCAAGGGCGTTTTGCTTTTCTAGTCTCATCTCTGCTCTGACGCTAAGCTCAAAGAGGGACTGGGGGACGGGAAG
ATATCCACCATGGCATGCGCCCTAGCTCTCGGGCTGGTGTTGGCTGCTTCCTTCTCAGATTCCAGAGTGCCTAGAGG
CCAGGAAAGGGAGAAGGTCCTACCAGCCTGGGGTAGGGACTCGGGGGCCAGGCACTGGCGCTGACGCAGGCTAGCAG
GGCGCCACTGGCTGGTCCCCACCCACCTCGGTGGGTTGGGGGATGGGCGCACCAGCCCCTCCTGGGTGAGCCCTAGC
CTGGGGCTTCCTATTTCGGGAGCCGGGGGCGTGGGCCACGTCTCCTCATGTGATGCGAGGGCTATTTAAAGCGGCAG
CCCGGGCAGGGAGCCGCCGTCGGAGCCCTTGCACGCCTGCTCTCTTGTAGCTTCTCTCAGCCTAGCCCAGCATCACT
ATGGTGGACGCTTTCCTGGGCACCTGGAAGCTAGTGGACAGCAAGAATTTCGATGACTACATGAAGTCACTCGGTGT
GGGTTTTGCTACCAGGCAGGTGGCCAGCATGACCAAGCCTACCACAATCATCGAAAAGAATGGGGACATTCTCACCC
TAAAAACACACAGCACCTTCAAGAACACAGAGATCAGCTTTAAGTTGGGGGTGGAGTTCGATGAGACAACAGCAGAT
GACAGGAAGGTCAAGTCCATTGTGACACTGGATGGAGGGAAACTTGTTCACCTGCAGAAATGGGACGGGCAAGAGAC
CACACTTGTGCGGGAGCTAATTGATGGAAAACTCATCCTGATGGAAAAACTGCAACTCAGAAATGTAAAGTGAGTCG
ACCAAGGCTAAAGCGGCAAAACCACTATACTTTATAACACAGAGTTTGGCACTATTTCCACTTTGTTCTCTCTCAAA
GATGAAGGCTCAGGAGGAGGGAAGATAAAAACAAATCACTGGAGAGTCCTGGCATGCTGGAACATGGACTCTAGCTA
GCAAGAAGGGCTCAAGGAGGTGGCCTTCTCCTAGACCTCAACTTTGATGCAAAAGCTGTTTTGCAGCCTGAACAAAG
ACAATCCAATCCTCCAGCAAATGGCGTCATTTTCCCTACGTGTCTAGCCTTGAGCTACAGAACAAAAGAACAATCAC
ATCCGAAGTTGTAGTTCGCCTGGTTGCGGTGGCTCACGCCTGTGATCCCAGCACTTTGGGAGGCCAAGGTGGGTGGA
TCACCTGAGGTCAGGAGGTCGAGACTAGCCTGACCAACATGAAGAAACCCCATCTCTACTAAAAATACAAAATTAGC
TGGGCGTGGTGGCACATGCCTGTAATCCCAGCTACTCGGGAGGCTGAGGCA
<210> SEQ ID NO 4
<211> Length: 3,531
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 4
>S67314_PEA_1_T7
TCTGCAGGAGGGGAGCTGGGAACGACCTGAGCTAAAGCTCGGAGCTGTGCGAAGAAACCGGAAAAGCCCAGAGCACT
TGCAGGGGCGGGTGGGGAGCTAGATGGTGGGGTGGGGTGGGGACGGAGGAGGGCCAGCAGGAGACATTCCGCAGGGA
GGGGCAAGCACGTGTGAGGCGGGCGGGGCGCGAAGGGTCAGGCTTTTGCTCAAAACAGGCAGAGGACAAGGTCAGCT
CAGCCGCAGACCGAGCCGCTGGTGACTGTCTCCGCCACCAGGCAGTGAGAGTGAAGGGAGAGCGCGAGCTCTGAAGC
CCGCTAGACTAAGCTTGCAATCTGAGCTCCATTCACCCCCTCCTATTTCTTGAGACCTTGTCAGTTCCCCTGTGAGC 500 CTCGGACTCCTCACTTGTAAAACGAGGACAGATGCCCGTGCCAGAAGTCAACCAGAGCTTTCCCCGGCGTGGGCACC
AGCCCAAGGGCGTTTTGCTTTTCTAGTCTCATCTCTGCTCTGACGCTAAGCTCAAAGAGGGACTGGGGGACGGGAAG
ATATCCACCATGGCATGCGCCCTAGCTCTCGGGCTGGTGTTGGCTGCTTCCTTCTCAGATTCCAGAGTGCCTAGAGG
CCAGGAAAGGGAGAAGGTCCTACCAGCCTGGGGTAGGGACTCGGGGGCCAGGCACTGGCGCTGACGCAGGCTAGCAG
GGCGCCACTGGCTGGTCCCCACCCACCTCGGTGGGTTGGGGGATGGGCGCACCAGCCCCTCCTGGGTGAGCCCTAGC
CTGGGGCTTCCTATTTCGGGAGCCGGGGGCGTGGGCCACGTCTCCTCATGTGATGCGAGGGCTATTTAAAGCGGCAG
CCCGGGCAGGGAGCCGCCGTCGGAGCCCTTGCACGCCTGCTCTCTTGTAGCTTCTCTCAGCCTAGCCCAGCATCACT
ATGGTGGACGCTTTCCTGGGCACCTGGAAGCTAGTGGACAGCAAGAATTTCGATGACTACATGAAGTCACTCGCTCA
TATACTCATAACCTTCCCCCTACCCTCAGGTGTGGGTTTTGCTACCAGGCAGGTGGCCAGCATGACCAAGCCTACCA
CAATCATCGAAAAGAATGGGGACATTCTCACCCTAAAAACACACAGCACCTTCAAGAACACAGAGATCAGCTTTAAG
TTGGGGGTGGAGTTCGATGAGACAACAGCAGATGACAGGAAGGTCAAGTCCATTGTGACACTGGATGGAGGGAAACT
TGTTCACCTGCAGAAATGGGACGGGCAAGAGACCACACTTGTGCGGGAGCTAATTGATGGAAAACTCATCCTGACAC
TCACCCACGGCACTGCAGTTTGCACTCGCACTTATGAGAAAGAGGCATGACCTGACTGCACTGTTGCTGACTACTAC
TCTGCCAATCGGCTACCCCTCGACTCAGCACCACATTGCCTCATTTCTTCCTCTGCATTTTGTACAAATCCACGAAT
TCTTCTGGGGTCAGGTGCCACTGACCGGGATCCAGTTCCAGTTCCCATGGTGTATGTGGTTTTTTTTTTTTTTTTTT
AACTGCACTCATAGGGTGCTCTGAGGTCAATAAAGCAGAGCCAAGGCCACCCAGTTGCCTTTTTGCCTTTGGTAACA
TAACTCTGGGAGTCTTGGTTTATCCTGTGTGTCAGAGAGTGGGCAGAAATAACGGCCTGAAGGTTACTGAGGAAGAA
GCACTGGATGGGAGACTGAAATGGACAGTCTCGGAGCCTGTTAATCAGCTGATCACCTTACACATTTAATAATAAAA
GAGCTGTACCTACACGTTGCCTTTACACTGCCCCCCCTCCATGGTCAAATGACCTAGTTCAGTCAGTGATGGGGCTT
CCCCAGGTTTGGCTATTGAACTGTCACTTCAGGCCCATCCTACACTGAAAGCTCTTGGGTCTGGCTGTTCTCTGTGA
AATGCTGTAGTCTCTCCCTTTCCAGAATTCAGGTTCAGGGCACAGAACCCAGGCTTGTACCATGGTGGTGGGAGAAA
ATGACCACTGGCCAAGAGGACTGCTGACCTGTGCACCAGGCTAGTACTTATGACTACAAATTCTTACTGCTTCTCTA
ATCAACTCTGAGGGAAGAGGGCATCTGATCATTACAAAAGGGAGGGCTTATAAGTGATCTCCCAAGAAGGCAGTGAT
CTGCTAGTGCCTTTGGCTCTGTACCTCTGCTGGGCATCTCTCCAAGGTCTAAGGTAACATATTAAATGTTTTTGTCA
GCTAATGCAGGCTCAGTGACTTTAAGTCTGTAAGTTACCCAGGAAGAAGGATTATAGGAAAAATAACTCAGTAAGTT
TAAAACCAAACACATTTCCATTTAGTGACAGGAATTTAAGCAAGGACCTGAAGTAGAATCAACTGATTCACACAGTA
GTAAATACAAAGTAGAACAATGATCTTGGCTTCGCTGTCTGGTTCAGTGGTCTGCTGGAATGCAATACACAAGTTAA
GTCACACTGCAGACTGTTTTCTAGCTGTGGCCGCTGGATGCCACTTCTAGCATAGTAGAACTATGTTAGGAGGAATG
GGAAAAGTGAGCACCACTTCTCACCATGTTCCCCCCTCCTGCTGCCAGTCTCTGCTCCCATGTTGGATGCAGCAGAG
ATCACCCACCAGTTGGCCCAGGACAGACCAATAGGAAGGGTCCAATCACTCTAACTACAGCCGAACTCACCTCCACA
ACAGTCTCTGTGGCTCTAGCCTGGACTCCTTTACAGGAATCCAGCTCTGGCAGTGGCAGCTGGAGAGGGTAATAGGG
CCTCCTGCTGAATGAAGGAAGTTGGGTGAATGAATGGGTGAGCTGCAGGGTTCACTTGCAAAGGGACCAGGAGTGAT
AAGGAAACAACAACTCATTCAGGCAGCTGCTTTTGACCTCTAACTCCCAAACCTGCCTGTTGCATGAGGGGAAGCCA
TCTCCCATGGGAGCGAAGTTAATGGGGTGGGAGGCTATATTCTCACTATTGAGTCTTTCCAGGAGTCTCAAGGCACA
AGGCTCCTGGTTTCTTACTCTCAACCACCCCCTACACTCTTTATACTCTCACTCCTTGTGCTTCTTCTTGTGCTTCT
TCTTCTTTTTCTTCTTCTTTGCTGCCTTGCTGTCTTTTGATGTGTGCCTTGCCCTCTTGCCTGTATCACTCTCAGAG
TCTGAGCTGTCAGAGTCAGATGACTTCCTATCTCTATGTTTCTTTTTCTTCTTCTCCTGAAAAGAAAATTTTAAAAA
TCAACACTGTATGTGTATATTTGCTTTTAACAATCATAGCACATAATTGGCCAGGTGCAGTGGCTCACACCTGTAAT 501 CCTAGTACTTTGGGAAGCCGAGGTGGGAGGAATGCTTGAGGCCAGGAGTTCAAGATCAACCTGGCTAACATAGCAAG
ATCTCATCTCTAAAAAGAGAAAAAAAGAAAAATTATAGCACACAATCAATAGGGGACCACTTAATTTTCTTTTAGAC
AGTCTCGCTCTGTTGCCCAGGCTAGAGTGCAGTGCAGTGGCACGATCACAGCTCACTGCAACCTCA
<210> SEQ ID NO 5
<211> Length: 2,778
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 5
>N56180_T1
ATGCGTGCGTGCGTGCGTGCGTGTGTGTGTGTGTGTGCCTCTGCTCTTTGTCCTGAGCCCACGATTCCAGAGCTGGC
TGGACCCAAGGAGGTGAAGAGTCACTTTTCAGCCCCAGGAAGGGCAAAGAAGAGAGAAAATCAGCCTGTCTGCTCTC
TCCTTGGCTCAACAAGGCCTCTAACAGTCTTCTGTCCTCTATTCTGCACACGGCATATTTGGGAACGAGAAACAAAA
GTTTTCCCAAATGAAGAGAACTCACTTGTTTATTGTGGGGATTTATTTTCTGTCCTCTTGCAGGGCAGAAGAGGGGC
TTAATTTCCCCACATATGATGGGAAGGACCGAGTGGTAAGTCTTTCCGAGAAGAACTTCAAGCAGGTTTTAAAGAAA
TATGACTTGCTTTGCCTCTACTACCATGAGCCGGTGTCTTCAGATAAGGTCACGCAAAAACAGTTCCAACTGAAAGA
AATCGTGCTTGAGCTTGTGGCCCAGGTCCTTGAACATAAAGCTATAGGCTTTGTGATGGTGGATGCCAAGAAAGAAG
CCAAGCTTGCCAAGAAACTGGGTTTTGATGAAGAAGGAAGCCTGTATATTCTTAAGGGTGATCGCACAATAGAGTTT
GATGGCGAGTTTGCAGCTGATGTCTTGGTGGAGTTCCTCTTGGATCTAATTGAAGACCCAGTGGAGATCATCAGCAG
CAAACTGGAAGTCCAAGCCTTCGAACGCATTGAAGACTACATCAAACTCATTGGCTTTTTCAAGAGTGAGGACTCAG
AATACTACAAGGCTTTTGAAGAAGCAGCTGAACACTTCCAGCCTTACATCAAATTCTTTGCCACCTTTGACAAAGGG
GTGCTGTGGCTCACACCTGTAATCCCAACACTTTGGGAGGCTGACGGGGGTGGATTGCATGAGCCTTGGAGTTGGAG
ACCAGCCTGGGCAACATGGTTGCAAAGAAATTATCTTTGAAGATGAATGAGGTTGACTTCTATGAGCCATTTATGGA
TGAGCCCATTGCCATCCCCAACAAACCTTACACAGAAGAGGAGCTGGTGGAGTTTGTGAAGGAACACCAAAGACCCA
CTCTACGTCGCCTGCGCCCAGAAGAAATGTTTGAAACATGGGAAGATGATTTGAATGGGATCCACATTGTGGCCTTT
GCAGAGAAGAGTGATCCAGATGGCTACGAATTCCTGGAGATCCTGAAACAGGTTGCCCGGGACAATACTGACAACCC
CGATCTGAGCATCCTGTGGATCGACCCGGACGACTTTCCTCTGCTCGTTGCCTACTGGGAGAAGACTTTCAAGATTG
ACCTATTCAGGCCACAGATTGGGGTGGTGAATGTCACAGATGCTGACAGTGTCTGGATGGAGATTCCAGATGATGAC
GATCTTCCAACTGCTGAGGAGCTGGAGGACTGGATTGAGGATGTGCTTTCTGGAAAGATAAACACTGAAGATGATGA
TGAAGATGATGATGATGATGATAATTCTGATGAAGAGGATAATGATGACAGTGATGACGATGATGATGAATAGCCCA
ACTCCAAACAATTCTGATGAAAACAAAATCACAGCACCCACTACCATACAGACAGCACAAGGTGGCAGCAAGCAATT
CTGCCCCACACCCAGCCAGCTCCTTTCCCTTTTCCATCATCTCTTTTCCCACTCCCTTTGCGTCAGGAGCAGCATCA
TTCAGCAAATGCCTTTTCAAATGCAGCAATCCCACTTAGCAGGGACAGGAGAAAAATTATTCCCATGTTGACTGTCT
TGACTGTCACGGAACAGATCTTGTTCTTTGCTGGACCATCAAGGGTCATGGCAGTGCCTGAACATGGCAGTCTAGGG
TGAACAATCCCCTAACACAAGTTTACTTGTCTTTGATTATGACAGTAACAAAATTGACAGCTTTCTAACTCACAGGC
ATAGAGTGACCTTTTAATCAGAGCCCAGGGAAGACACATGATTAATGATTTAGCTCCCTCCATACCTCGAACATCAG
TTGGGATCCCTCCTCCAGCCAAGATGATCCTTCTTAGAGAAGGCTCAGCCTTGGAAGCAAACTTATAAATCATATTC 502 TCATGGCTTTGTTAAACTTATTTCAAGTGATGGTCATTCATATCACTATGAACTTGGATATTCAAGCCTTTGGATGG
CTATGGAGAGGCCTTGAAATGTGTACAGGTGTCACCATCATTTCTAGTATATTAGGAAACTGGGATGGGAGGTTGAT
TTGCTCTCTAAACTTCCCTCTAGTTGGCAAGTCTCACATATTCATCAGCAGGAGTGGAGGGTGGGGGAAAACTAGAA
AGATGAAAACTTTTACATTTTTCTGATGGGTTCATGTCTCTGATTGGGTCAGCTGGCTTCCTAGCCTAAGCTGGGAT
CTGAATACCCCTTCTCTGTAGCTGCTAGTGAGCCTTCCCATTTAGATTAAAGATTGCTTTATCCAGCAGTCAATTAA
CTCTCCAGTTATCAGTACTCCCACAATTGGCCAGGGCAACAATAATTGGAGTTCATACTGATGCCCTGAGGCACTGA
AAAAAAAAAAAATCCCAAAGTGCCTTCTGAGCTGTCTAAAAGTTACATTGTGCTTGGTAGATTTAGTGTTAAGTGTG
CAGTATAATTTTCTAATTTATTTTCTCAATCTTTTAGCACATGTGTAAGACACTGTGCAAATTTTTTGAAAATAGAG
CAATACTTTTTGTGGAATACTAGCTAACTAATTCTGTCATTAAACTCATATTTTGAAAATATTCAGACAATGTTGAA
AATCCT
<210> SEQ ID NO 6
<211> Length: 2,824
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 6
>N56180_T3
ATGCGTGCGTGCGTGCGTGCGTGTGTGTGTGTGTGTGCCTCTGCTCTTTGTCCTGAGCCCACGATTCCAGAGCTGGC
TGGACCCAAGGAGGTGAAGAGTCACTTTTCAGCCCCAGGAAGGGCAAAGAAGAGAGAAAATCAGCCTGTCTGCTCTC
TCCTTGGCTCAACAAGGCCTCTAACAGTCTTCTGTCCTCTATTCTGCACACGGCATATTTGGGAACGAGAAACAAAA
GTTTTCCCAAATGAAGAGAACTCACTTGTTTATTGTGGGGATTTATTTTCTGTCCTCTTGCAGGGCAGAAGAGGGGC
TTAATTTCCCCACATATGATGGGAAGGACCGAGTGGTAAGTCTTTCCGAGAAGAACTTCAAGCAGGTTTTAAAGAAA
TATGACTTGCTTTGCCTCTACTACCATGAGCCGGTGTCTTCAGATAAGGTCACGCAAAAACAGTTCCAACTGAAAGA
AATCGTGCTTGAGCACTGGCAAATATCCCAGTGGTGGTTGCATTTCCAAACCCCAAGAGAGGAAGGCAAAATGAAGT
TGCTGGAGTTGAGTGAATCTGCAGATGGAGCTGCGTGGAAACGCTGGGGAGGGAATAGCAACACACACAGGATTCAG
CTTGTGGCCCAGGTCCTTGAACATAAAGCTATAGGCTTTGTGATGGTGGATGCCAAGAAAGAAGCCAAGCTTGCCAA
GAAACTGGGTTTTGATGAAGAAGGAAGCCTGTATATTCTTAAGGGTGATCGCACAATAGAGTTTGATGGCGAGTTTG
CAGCTGATGTCTTGGTGGAGTTCCTCTTGGATCTAATTGAAGACCCAGTGGAGATCATCAGCAGCAAACTGGAAGTC
CAAGCCTTCGAACGCATTGAAGACTACATCAAACTCATTGGCTTTTTCAAGAGTGAGGACTCAGAATACTACAAGGC
TTTTGAAGAAGCAGCTGAACACTTCCAGCCTTACATCAAATTCTTTGCCACCTTTGACAAAGGGGTTGCAAAGAAAT
TATCTTTGAAGATGAATGAGGTTGACTTCTATGAGCCATTTATGGATGAGCCCATTGCCATCCCCAACAAACCTTAC
ACAGAAGAGGAGCTGGTGGAGTTTGTGAAGGAACACCAAAGACCCACTCTACGTCGCCTGCGCCCAGAAGAAATGTT
TGAAACATGGGAAGATGATTTGAATGGGATCCACATTGTGGCCTTTGCAGAGAAGAGTGATCCAGATGGCTACGAAT
TCCTGGAGATCCTGAAACAGGTTGCCCGGGACAATACTGACAACCCCGATCTGAGCATCCTGTGGATCGACCCGGAC
GACTTTCCTCTGCTCGTTGCCTACTGGGAGAAGACTTTCAAGATTGACCTATTCAGGCCACAGATTGGGGTGGTGAA
TGTCACAGATGCTGACAGTGTCTGGATGGAGATTCCAGATGATGACGATCTTCCAACTGCTGAGGAGCTGGAGGACT
GGATTGAGGATGTGCTTTCTGGAAAGATAAACACTGAAGATGATGATGAAGATGATGATGATGATGATAATTCTGAT 503 GAAGAGGATAATGATGACAGTGATGACGATGATGATGAATAGCCCAACTCCAAACAATTCTGATGAAAACAAAATCA
CAGCACCCACTACCATACAGACAGCACAAGGTGGCAGCAAGCAATTCTGCCCCACACCCAGCCAGCTCCTTTCCCTT
TTCCATCATCTCTTTTCCCACTCCCTTTGCGTCAGGAGCAGCATCATTCAGCAAATGCCTTTTCAAATGCAGCAATC
CCACTTAGCAGGGACAGGAGAAAAATTATTCCCATGTTGACTGTCTTGACTGTCACGGAACAGATCTTGTTCTTTGC
TGGACCATCAAGGGTCATGGCAGTGCCTGAACATGGCAGTCTAGGGTGAACAATCCCCTAACACAAGTTTACTTGTC
TTTGATTATGACAGTAACAAAATTGACAGCTTTCTAACTCACAGGCATAGAGTGACCTTTTAATCAGAGCCCAGGGA
AGACACATGATTAATGATTTAGCTCCCTCCATACCTCGAACATCAGTTGGGATCCCTCCTCCAGCCAAGATGATCCT
TCTTAGAGAAGGCTCAGCCTTGGAAGCAAACTTATAAATCATATTCTCATGGCTTTGTTAAACTTATTTCAAGTGAT
GGTCATTCATATCACTATGAACTTGGATATTCAAGCCTTTGGATGGCTATGGAGAGGCCTTGAAATGTGTACAGGTG
TCACCATCATTTCTAGTATATTAGGAAACTGGGATGGGAGGTTGATTTGCTCTCTAAACTTCCCTCTAGTTGGCAAG
TCTCACATATTCATCAGCAGGAGTGGAGGGTGGGGGAAAACTAGAAAGATGAAAACTTTTACATTTTTCTGATGGGT
TCATGTCTCTGATTGGGTCAGCTGGCTTCCTAGCCTAAGCTGGGATCTGAATACCCCTTCTCTGTAGCTGCTAGTGA
GCCTTCCCATTTAGATTAAAGATTGCTTTATCCAGCAGTCAATTAACTCTCCAGTTATCAGTACTCCCACAATTGGC
CAGGGCAACAATAATTGGAGTTCATACTGATGCCCTGAGGCACTGAAAAAAAAAAAAATCCCAAAGTGCCTTCTGAG
CTGTCTAAAAGTTACATTGTGCTTGGTAGATTTAGTGTTAAGTGTGCAGTATAATTTTCTAATTTATTTTCTCAATC
TTTTAGCACATGTGTAAGACACTGTGCAAATTTTTTGAAAATAGAGCAATACTTTTTGTGGAATACTAGCTAACTAA
TTCTGTCATTAAACTCATATTTTGAAAATATTCAGACAATGTTGAAAATCCT
<210> SEQ ID NO 7
<211> Length: 2,497
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 7
>N56180_T4
ATGCGTGCGTGCGTGCGTGCGTGTGTGTGTGTGTGTGCCTCTGCTCTTTGTCCTGAGCCCACGATTCCAGAGCTGGC
TGGACCCAAGGAGGTGAAGAGTCACTTTTCAGCCCCAGGAAGGGCAAAGAAGAGAGAAAATCAGCCTGTCTGCTCTC
TCCTTGGCTCAACAAGGCCTCTAACAGTCTTCTGTCCTCTATTCTGCACACGGCATATTTGGGAACGAGAAACAAAA
GTTTTCCCAAATGAAGAGAACTCACTTGTTTATTGTGGGGATTTATTTTCTGTCCTCTTGCAGGGCAGAAGAGGGGC
TTAATTTCCCCACATATGATGGGAAGGACCGAGTGGTAAGTCTTTCCGAGAAGAACTTCAAGCAGGTTTTAAAGAAA
TATGACTTGCTTTGCCTCTACTACCATGAGCCGGTGTCTTCAGATAAGGTCACGCAAAAACAGTTCCAACTGAAAGA
AATCGTGCTTGAGCTTGTGGCCCAGGTCCTTGAACATAAAGCTATAGGCTTTGTGATGGTGGATGCCAAGAAAGAAG
CCAAGCTTGCCAAGAAACTGGGTTTTGATGAAGAAGGAAGCCTGTATATTCTTAAGGGTGATCGCACAATAGAGTTT
GATGGCGAGTTTGCAGCTGATGTCTTGGTGGAGTTCCTCTTGGATGTTGCAAAGAAATTATCTTTGAAGATGAATGA
GGTTGACTTCTATGAGCCATTTATGGATGAGCCCATTGCCATCCCCAACAAACCTTACACAGAAGAGGAGCTGGTGG
AGTTTGTGAAGGAACACCAAAGACCCACTCTACGTCGCCTGCGCCCAGAAGAAATGTTTGAAACATGGGAAGATGAT
TTGAATGGGATCCACATTGTGGCCTTTGCAGAGAAGAGTGATCCAGATGGCTACGAATTCCTGGAGATCCTGAAACA
GGTTGCCCGGGACAATACTGACAACCCCGATCTGAGCATCCTGTGGATCGACCCGGACGACTTTCCTCTGCTCGTTG 504 CCTACTGGGAGAAGACTTTCAAGATTGACCTATTCAGGCCACAGATTGGGGTGGTGAATGTCACAGATGCTGACAGT
GTCTGGATGGAGATTCCAGATGATGACGATCTTCCAACTGCTGAGGAGCTGGAGGACTGGATTGAGGATGTGCTTTC
TGGAAAGATAAACACTGAAGATGATGATGAAGATGATGATGATGATGATAATTCTGATGAAGAGGATAATGATGACA
GTGATGACGATGATGATGAATAGCCCAACTCCAAACAATTCTGATGAAAACAAAATCACAGCACCCACTACCATACA
GACAGCACAAGGTGGCAGCAAGCAATTCTGCCCCACACCCAGCCAGCTCCTTTCCCTTTTCCATCATCTCTTTTCCC
ACTCCCTTTGCGTCAGGAGCAGCATCATTCAGCAAATGCCTTTTCAAATGCAGCAATCCCACTTAGCAGGGACAGGA
GAAAAATTATTCCCATGTTGACTGTCTTGACTGTCACGGAACAGATCTTGTTCTTTGCTGGACCATCAAGGGTCATG
GCAGTGCCTGAACATGGCAGTCTAGGGTGAACAATCCCCTAACACAAGTTTACTTGTCTTTGATTATGACAGTAACA
AAATTGACAGCTTTCTAACTCACAGGCATAGAGTGACCTTTTAATCAGAGCCCAGGGAAGACACATGATTAATGATT
TAGCTCCCTCCATACCTCGAACATCAGTTGGGATCCCTCCTCCAGCCAAGATGATCCTTCTTAGAGAAGGCTCAGCC
TTGGAAGCAAACTTATAAATCATATTCTCATGGCTTTGTTAAACTTATTTCAAGTGATGGTCATTCATATCACTATG
AACTTGGATATTCAAGCCTTTGGATGGCTATGGAGAGGCCTTGAAATGTGTACAGGTGTCACCATCATTTCTAGTAT
ATTAGGAAACTGGGATGGGAGGTTGATTTGCTCTCTAAACTTCCCTCTAGTTGGCAAGTCTCACATATTCATCAGCA
GGAGTGGAGGGTGGGGGAAAACTAGAAAGATGAAAACTTTTACATTTTTCTGATGGGTTCATGTCTCTGATTGGGTC
AGCTGGCTTCCTAGCCTAAGCTGGGATCTGAATACCCCTTCTCTGTAGCTGCTAGTGAGCCTTCCCATTTAGATTAA
AGATTGCTTTATCCAGCAGTCAATTAACTCTCCAGTTATCAGTACTCCCACAATTGGCCAGGGCAACAATAATTGGA
GTTCATACTGATGCCCTGAGGCACTGAAAAAAAAAAAAATCCCAAAGTGCCTTCTGAGCTGTCTAAAAGTTACATTG
TGCTTGGTAGATTTAGTGTTAAGTGTGCAGTATAATTTTCTAATTTATTTTCTCAATCTTTTAGCACATGTGTAAGA
CACTGTGCAAATTTTTTGAAAATAGAGCAATACTTTTTGTGGAATACTAGCTAACTAATTCTGTCATTAAACTCATA
TTTTGAAAATATTCAGACAATGTTGAAAATCCT
<210> SEQ ID NO 8
<211> Length: 2,209
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 8
>N56180_T5
TAATGAGACAGAGGCTGAGCAGAGCTATGTAAGGGCAGAAGAGGGGCTTAATTTCCCCACATATGATGGGAAGGACC
GAGTGGTAAGTCTTTCCGAGAAGAACTTCAAGCAGGTTTTAAAGAAATATGACTTGCTTTGCCTCTACTACCATGAG
CCGGTGTCTTCAGATAAGGTCACGCAAAAACAGTTCCAACTGAAAGAAATCGTGCTTGAGCTTGTGGCCCAGGTCCT
TGAACATAAAGCTATAGGCTTTGTGATGGTGGATGCCAAGAAAGAAGCCAAGCTTGCCAAGAAACTGGACTACAAGG
CTTTTGAAGAAGCAGCTGAACACTTCCAGCCTTACATCAAATTCTTTGCCACCTTTGACAAAGGGGTTGCAAAGAAA
TTATCTTTGAAGATGAATGAGGTTGACTTCTATGAGCCATTTATGGATGAGCCCATTGCCATCCCCAACAAACCTTA
CACAGAAGAGGAGCTGGTGGAGTTTGTGAAGGAACACCAAAGACCCACTCTACGTCGCCTGCGCCCAGAAGAAATGT
TTGAAACATGGGAAGATGATTTGAATGGGATCCACATTGTGGCCTTTGCAGAGAAGAGTGATCCAGATGGCTACGAA
TTCCTGGAGATCCTGAAACAGGTTGCCCGGGACAATACTGACAACCCCGATCTGAGCATCCTGTGGATCGACCCGGA
CGACTTTCCTCTGCTCGTTGCCTACTGGGAGAAGACTTTCAAGATTGACCTATTCAGGCCACAGATTGGGGTGGTGA 505 ATGTCACAGATGCTGACAGTGTCTGGATGGAGATTCCAGATGATGACGATCTTCCAACTGCTGAGGAGCTGGAGGAC
TGGATTGAGGATGTGCTTTCTGGAAAGATAAACACTGAAGATGATGATGAAGATGATGATGATGATGATAATTCTGA
TGAAGAGGATAATGATGACAGTGATGACGATGATGATGAATAGCCCAACTCCAAACAATTCTGATGAAAACAAAATC
ACAGCACCCACTACCATACAGACAGCACAAGGTGGCAGCAAGCAATTCTGCCCCACACCCAGCCAGCTCCTTTCCCT
TTTCCATCATCTCTTTTCCCACTCCCTTTGCGTCAGGAGCAGCATCATTCAGCAAATGCCTTTTCAAATGCAGCAAT
CCCACTTAGCAGGGACAGGAGAAAAATTATTCCCATGTTGACTGTCTTGACTGTCACGGAACAGATCTTGTTCTTTG
CTGGACCATCAAGGGTCATGGCAGTGCCTGAACATGGCAGTCTAGGGTGAACAATCCCCTAACACAAGTTTACTTGT
CTTTGATTATGACAGTAACAAAATTGACAGCTTTCTAACTCACAGGCATAGAGTGACCTTTTAATCAGAGCCCAGGG
AAGACACATGATTAATGATTTAGCTCCCTCCATACCTCGAACATCAGTTGGGATCCCTCCTCCAGCCAAGATGATCC
TTCTTAGAGAAGGCTCAGCCTTGGAAGCAAACTTATAAATCATATTCTCATGGCTTTGTTAAACTTATTTCAAGTGA
TGGTCATTCATATCACTATGAACTTGGATATTCAAGCCTTTGGATGGCTATGGAGAGGCCTTGAAATGTGTACAGGT
GTCACCATCATTTCTAGTATATTAGGAAACTGGGATGGGAGGTTGATTTGCTCTCTAAACTTCCCTCTAGTTGGCAA
GTCTCACATATTCATCAGCAGGAGTGGAGGGTGGGGGAAAACTAGAAAGATGAAAACTTTTACATTTTTCTGATGGG
TTCATGTCTCTGATTGGGTCAGCTGGCTTCCTAGCCTAAGCTGGGATCTGAATACCCCTTCTCTGTAGCTGCTAGTG
AGCCTTCCCATTTAGATTAAAGATTGCTTTATCCAGCAGTCAATTAACTCTCCAGTTATCAGTACTCCCACAATTGG
CCAGGGCAACAATAATTGGAGTTCATACTGATGCCCTGAGGCACTGAAAAAAAAAAAAATCCCAAAGTGCCTTCTGA
GCTGTCTAAAAGTTACATTGTGCTTGGTAGATTTAGTGTTAAGTGTGCAGTATAATTTTCTAATTTATTTTCTCAAT
CTTTTAGCACATGTGTAAGACACTGTGCAAATTTTTTGAAAATAGAGCAATACTTTTTGTGGAATACTAGCTAACTA
ATTCTGTCATTAAACTCATATTTTGAAAATATTCAGACAATGTTGAAAATCCT
<210> SEQ ID NO 9
<211> Length: 2,209
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 9
>N56180_T6
TGCAGGCAAACAGCAACCATTCTGCCTTGACAACACACTGAACATGTGGCTGCTTTAATCCAGAGAGAAAATGTCTT
CCTGGCTATCGGCTGGCTCTCCGAGCTCTTTATCTGTTGTTGCAAAGAAATTATCTTTGAAGATGAATGAGGTTGAC
TTCTATGAGCCATTTATGGATGAGCCCATTGCCATCCCCAACAAACCTTACACAGAAGAGGAGCTGGTGGAGTTTGT
GAAGGAACACCAAAGACCCACTCTACGTCGCCTGCGCCCAGAAGAAATGTTTGAAACATGGGAAGATGATTTGAATG
GGATCCACATTGTGGCCTTTGCAGAGAAGAGTGATCCAGATGGCTACGAATTCCTGGAGATCCTGAAACAGGTTGCC
CGGGACAATACTGACAACCCCGATCTGAGCATCCTGTGGATCGACCCGGACGACTTTCCTCTGCTCGTTGCCTACTG
GGAGAAGACTTTCAAGATTGACCTATTCAGGCCACAGATTGGGGTGGTGAATGTCACAGATGCTGACAGTGTCTGGA
TGGAGATTCCAGATGATGACGATCTTCCAACTGCTGAGGAGCTGGAGGACTGGATTGAGGATGTGCTTTCTGGAAAG
ATAAACACTGAAGATGATGATGAAGATGATGATGATGATGATAATTCTGATGAAGAGGATAATGATGACAGTGATGA
CGATGATGATGAATAGCCCAACTCCAAACAATTCTGATGAAAACAAAATCACAGCACCCACTACCATACAGACAGCA
CAAGGTGGCAGCAAGCAATTCTGCCCCACACCCAGCCAGCTCCTTTCCCTTTTCCATCATCTCTTTTCCCACTCCCT 506
TTGCGTCAGGAGCAGCATCATTCAGCAAATGCCTTTTCAAATGCAGCAATCCCACTTAGCAGGGACAGGAGAAAAAT
TATTCCCATGTTGACTGTCTTGACTGTCACGGAACAGATCTTGTTCTTTGCTGGACCATCAAGGGTCATGGCAGTGC CTGAACATGGCAGTCTAGGGTGAACAATCCCCTAACACAAGTTTACTTGTCTTTGATTATGACAGTAACAAAATTGA CAGCTTTCTAACTCACAGGCATAGAGTGACCTTTTAATCAGAGCCCAGGGAAGACACATGATTAATGATTTAGCTCC CTCCATACCTCGAACATCAGTTGGGATCCCTCCTCCAGCCAAGATGATCCTTCTTAGAGAAGGCTCAGCCTTGGAAG CAAACTTATAAATCATATTCTCATGGCTTTGTTAAACTTATTTCAAGTGATGGTCATTCATATCACTATGAACTTGG ATATTCAAGCCTTTGGATGGCTATGGAGAGGCCTTGAAATGTGTACAGGTGTCACCATCATTTCTAGTATATTAGGA AACTGGGATGGGAGGTTGATTTGCTCTCTAAACTTCCCTCTAGTTGGCAAGTCTCACATATTCATCAGCAGGAGTGG AGGGTGGGGGAAAACTAGAAAGATGAAAACTTTTACATTTTTCTGATGGGTTCATGTCTCTGATTGGGTCAGCTGGC TTCCTAGCCTAAGCTGGGATCTGAATACCCCTTCTCTGTAGCTGCTAGTGAGCCTTCCCATTTAGATTAAAGATTGC TTTATCCAGCAGTCAATTAACTCTCCAGTTATCAGTACTCCCACAATTGGCCAGGGCAACAATAATTGGAGTTCATA CTGATGCCCTGAGGCACTGAAAAAAAAAAAAATCCCAAAGTGCCTTCTGAGCTGTCTAAAAGTTACATTGTGCTTGG TAGATTTAGTGTTAAGTGTGCAGTATAATTTTCTAATTTATTTTCTCAATCTTTTAGCACATGTGTAAGACACTGTG CAAATTTTTTGAAAATAGAGCAATACTTTTTGTGGAATACTAGCTAACTAATTCTGTCATTAAACTCATATTTTGAA AATATTCAGACAATGTTGAAAATCCT
<210> SEQ ID NO 10
<211> Length: 1,740
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 10
>N56180_T7
TCTATAGAATAATCCTATAATTGAGGGTGAGCACCAAATGTCCTAAGAAGTCCTCGTGGAAAAATCACACTCTGCTC
TCCACATTAGAAGCTGTGTATGTGCAGGGGTTACTCAACTCTCTTGAATCCTGTTTCAGATGGCTACGAATTCCTGG
AGATCCTGAAACAGGTTGCCCGGGACAATACTGACAACCCCGATCTGAGCATCCTGTGGATCGACCCGGACGACTTT
CCTCTGCTCGTTGCCTACTGGGAGAAGACTTTCAAGATTGACCTATTCAGGCCACAGATTGGGGTGGTGAATGTCAC
AGATGCTGACAGTGTCTGGATGGAGATTCCAGATGATGACGATCTTCCAACTGCTGAGGAGCTGGAGGACTGGATTG
AGGATGTGCTTTCTGGAAAGATAAACACTGAAGATGATGATGAAGATGATGATGATGATGATAATTCTGATGAAGAG
GATAATGATGACAGTGATGACGATGATGATGAATAGCCCAACTCCAAACAATTCTGATGAAAACAAAATCACAGCAC
CCACTACCATACAGACAGCACAAGGTGGCAGCAAGCAATTCTGCCCCACACCCAGCCAGCTCCTTTCCCTTTTCCAT
CATCTCTTTTCCCACTCCCTTTGCGTCAGGAGCAGCATCATTCAGCAAATGCCTTTTCAAATGCAGCAATCCCACTT
AGCAGGGACAGGAGAAAAATTATTCCCATGTTGACTGTCTTGACTGTCACGGAACAGATCTTGTTCTTTGCTGGACC
ATCAAGGGTCATGGCAGTGCCTGAACATGGCAGTCTAGGGTGAACAATCCCCTAACACAAGTTTACTTGTCTTTGAT
TATGACAGTAACAAAATTGACAGCTTTCTAACTCACAGGCATAGAGTGACCTTTTAATCAGAGCCCAGGGAAGACAC
ATGATTAATGATTTAGCTCCCTCCATACCTCGAACATCAGTTGGGATCCCTCCTCCAGCCAAGATGATCCTTCTTAG
AGAAGGCTCAGCCTTGGAAGCAAACTTATAAATCATATTCTCATGGCTTTGTTAAACTTATTTCAAGTGATGGTCAT
TCATATCACTATGAACTTGGATATTCAAGCCTTTGGATGGCTATGGAGAGGCCTTGAAATGTGTACAGGTGTCACCA 507 TCATTTCTAGTATATTAGGAAACTGGGATGGGAGGTTGATTTGCTCTCTAAACTTCCCTCTAGTTGGCAAGTCTCAC
ATATTCATCAGCAGGAGTGGAGGGTGGGGGAAAACTAGAAAGATGAAAACTTTTACATTTTTCTGATGGGTTCATGT
CTCTGATTGGGTCAGCTGGCTTCCTAGCCTAAGCTGGGATCTGAATACCCCTTCTCTGTAGCTGCTAGTGAGCCTTC
CCATTTAGATTAAAGATTGCTTTATCCAGCAGTCAATTAACTCTCCAGTTATCAGTACTCCCACAATTGGCCAGGGC
AACAATAATTGGAGTTCATACTGATGCCCTGAGGCACTGAAAAAAAAAAAAATCCCAAAGTGCCTTCTGAGCTGTCT
AAAAGTTACATTGTGCTTGGTAGATTTAGTGTTAAGTGTGCAGTATAATTTTCTAATTTATTTTCTCAATCTTTTAG
CACATGTGTAAGACACTGTGCAAATTTTTTGAAAATAGAGCAATACTTTTTGTGGAATACTAGCTAACTAATTCTGT
CATTAAACTCATATTTTGAAAATATTCAGACAATGTTGAAAATCCT
<210> SEQ ID NO 11
<211> Length: 1,259
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 11
ATGCGTGCGTGCGTGCGTGCGTGTGTGTGTGTGTGTGCCTCTGCTCTTTGTCCTGAGCCCACGATTCCAGAGCTGGC
TGGACCCAAGGAGGTGAAGAGTCACTTTTCAGCCCCAGGAAGGGCAAAGAAGAGAGAAAATCAGCCTGTCTGCTCTC
TCCTTGGCTCAACAAGGCCTCTAACAGTCTTCTGTCCTCTATTCTGCACACGGCATATTTGGGAACGAGAAACAAAA
GTTTTCCCAAATGAAGAGAACTCACTTGTTTATTGTGGGGATTTATTTTCTGTCCTCTTGCAGGGCAGAAGAGGGGC
TTAATTTCCCCACATATGATGGGAAGGACCGAGTGGTAAGTCTTTCCGAGAAGAACTTCAAGCAGGTTTTAAAGAAA
TATGACTTGCTTTGCCTCTACTACCATGAGCCGGTGTCTTCAGATAAGGTCACGCAAAAACAGTTCCAACTGAAAGA
AATCGTGCTTGAGCTTGTGGCCCAGGTCCTTGAACATAAAGCTATAGGCTTTGTGATGGTGGATGCCAAGAAAGAAG
CCAAGCTTGCCAAGAAACTGGGTTTTGATGAAGAAGGAAGCCTGTATATTCTTAAGGGTGATCGCACAATAGAGTTT
GATGGCGAGTTTGCAGCTGATGTCTTGGTGGAGTTCCTCTTGGATCTAATTGAAGACCCAGTGGAGATCATCAGCAG
CAAACTGGAAGTCCAAGCCTTCGAACGCATTGAAGACTACATCAAACTCATTGGCTTTTTCAAGAGTGAGGACTCAG
AATACTACAAGGCTTTTGAAGAAGCAGCTGAACACTTCCAGCCTTACATCAAATTCTTTGCCACCTTTGACAAAGGG
GTTGCAAAGAAATTATCTTTGAAGATGAATGAGGTTGACTTCTATGAGCCATTTATGGATGAGCCCATTGCCATCCC
CAACAAACCTTACACAGAAGAGGAGCTGGTGGAGTTTGTGAAGGAACACCAAAGATCAAGGAATTGGACTCAATAGT
TAAGTAACTTAGCCAAGGATGAACACTCTATGCATAGAACTTCTGGGAGAGAAATGCTTGATACCACTTAGTGTAGC
TCCAGCATGGATCAGCAAACTTTTTCTGTAAAGAACAAAATGGTAAATATTTCAGGTTCTGTGGGCCAGATGGCGTC
TGTAGCAACTACTTGACTGCGGCTGTGGCATGAAAGCAGCCATGGATCATGTATAAACAAATGGGTGTGGCTGTGTA
CCAGTAAAAGTTTATCCGGAAAAAAAG
<210> SEQ ID NO 12
<211> Length: 2,412
<212> Type: DNA
<213> ORGANISM: Homo sapiens 508
<400> sequence: 12
>T10377_T0
GGGGGGGCCTTCGCGGTGCAGCTGAGGCTGCAAGTAGCCGGCGCCGTCCCGCGTCGCCCCCGCGCAGGGCGGGCCCC
GCACGCTTATCCTGCCCGGGAGGAACGCCGGCGTCCAGCCCGCTACCGACCGCCGCTGCGGGATGCTGCGCTCCACG
TCCACGGTCACCCTGCTCTCGGGCGGCGCCGCCAGGACGCCCGGGGCGCCCAGCAGGAGGGCAAATGTTTGCAGACT
ACGGCTGACCGTACCTCCTGAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAGAAAAGAGCAGCTTCTTG
ACCTGAGCAATGGAGAACCTACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAGATCAAAAT
CAGCAGAAAGAAATGGTGGTGTATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAAGATGTGAG
AGCCACTTTGGAAAAGGTGAGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACAGCTCACCC
AGGAACTATCAGTTTCCCATGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCCTGGATCGT
TTTAATGCCATGAACTCAGCCTTGGCATCAGATTCCATTGGCCTGCAGAAAACCCTCGTGGATGTGACTTTGGAAAA
CAGCAACATTAAGGATCAAATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGGAAAAGCAGA
GGCAGTTGGAGGTAGCGCAAGTTGAAAACCAGCTGCTAAAAATGAAGGTGGAATCGTCCCAAGAAGCCAATGCTGAG
GTGATGCGAGAGATGACCAAGAAGCTGTACAGCCAGTATGAGGAGAAGCTGCAGGAAGAACAGAGGAAGCACAGTGC
TGAGAAGGAGGCTCTTTTGGAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGATGCAAGCAG
CAGAGATCAGCCTAGAGGAGAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAAAGGAACGT
CATCAACTGCAACTTCAACTCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAGGAAAGGTA
TCAGCAGTTGGAGGAGGCATCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTGCCAGCAGA
AGAAAGTCAAGCAGATGGTCGAGGAGATTGAATCATTAAAGAAAAAGTTGCAACAGAAACAGCTCTTAATACTGCAG
CTTTTAGAAAAGATATCTTTCTTAGAAGGAGAGAATAATGAACTACAAAGCAGGTTGGACTATTTAACAGAAACCCA
GGCCAAGACCGAAGTGGAAACCAGAGAGATAGGAGTGGGCTGTGATCTTCTACCCAGCCAAACAGGCAGGACTCGTG
AAATTGTGATGCCTTCTAGGAACTACACCCCATACACAAGAGTCCTGGAGTTAACCATGAAGAAAACTCTGACTTAG
GCACTCAGAGGCATACACTTTTTACAGATGGACAAAAGCTCTGGAACCCTGTGGCTTCAAATCCTTTGGGAAGGGTG
ACTGTTGTTTCCCCTACACACAGTGTAAGCCGGAATGGGAATCGCTGAGGCTCTGATCCACTTCTAAGACAGGAAGG
AAAGTGAAGGCAGAGTGAGCAGGTAAGAGAGGGATATACAAGGTCACATTTCAGACACCCACTCGGCATACCCTGCC
GTACTGCATCATCATTTGTTTTCTTTGTAGACACTGAAATCCTATCAGGAGGATTCCTTCACAATGTATTTTATTTG
CTAGACTTTGGTTGGGAGGGAAAAGGACATTAATTTGAAGTTTCATGTTATTCATGCCAGGATTGTTTGATAGAGCA
TGAAGGTTTTGTTTACCCATAAAAGTATTAGAGGCAGCGTTTCTCTGATACAGAGAGGCCTGTCCACAAGAAGCATG
GGCACCCAGCCAAACTTGAACCTGGAAGGGAGGGTTCCCGGCCTGCAGGTGCTCTTTCCTCTTGGTCCCAAGCATCT
GTGCAGGGTCGTGGGAGCCACACTGAGAGACTTGTGTGGGCCAGACAAGCTTCATTCTGATGCGCTAGTCCCTTGGT
TTAATTTGTGCCTTATGCTTTCATTGGACCAGCTGAAATCACTGTATTTATTCAACTTGTGATTTTTTTTTCTTTCT
CACTTTAACTTAAAGAGAATTTTATATGTCTTGGAAATTTAATAATTTAGTGTTCTCAGTATCAATTGGTGTTTTTG
TTAAACGAATGAATCATCTGTTCATGCATGCTCTACTTTGATATTATAACCTATGTCACATGTGTTTAATAAATACC
ATATATTTTGTTCTACTAAAAAAAT
<210> SEQ ID NO 13 <211> Length: 2,393 509 <212> Type : DNA
<213> ORGANI SM : Homo sapiens
< 400> sequence : 13
>T10377_T1
TAGCAGTGGTGTTCAGGGTAGGATGCAGTTCTTCGCATTGTGCATAACACAAGCCCTGAACCAGCTGCTTTGGGAAC
CCCTGGGAATAAAGTGCCCTACCTGCCTTTCAGGCACTGCCAAGCCTGGGGCATCTCTGGAGATTGTGTATCCGAGT
TTCAGGAGACCATGGAGATCAGCCTCGTAAAATGCTCGGAGGCAAATGTTTGCAGACTACGGCTGACCGTACCTCCT
GAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAGAAAAGAGCAGCTTCTTGACCTGAGCAATGGAGAACC
TACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAGATCAAAATCAGCAGAAAGAAATGGTGG
TGTATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAAGATGTGAGAGCCACTTTGGAAAAGGTG
AGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACAGCTCACCCAGGAACTATCAGTTTCCCA
TGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCCTGGATCGTTTTAATGCCATGAACTCAG
CCTTGGCATCAGATTCCATTGGCCTGCAGAAAACCCTCGTGGATGTGACTTTGGAAAACAGCAACATTAAGGATCAA
ATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGGAAAAGCAGAGGCAGTTGGAGGTAGCGCA
AGTTGAAAACCAGCTGCTAAAAATGAAGGTGGAATCGTCCCAAGAAGCCAATGCTGAGGTGATGCGAGAGATGACCA
AGAAGCTGTACAGCCAGTATGAGGAGAAGCTGCAGGAAGAACAGAGGAAGCACAGTGCTGAGAAGGAGGCTCTTTTG
GAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGATGCAAGCAGCAGAGATCAGCCTAGAGGA
GAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAAAGGAACGTCATCAACTGCAACTTCAAC
TCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAGGAAAGGTATCAGCAGTTGGAGGAGGCA
TCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTGCCAGCAGAAGAAAGTCAAGCAGATGGT
CGAGGAGATTGAATCATTAAAGAAAAAGTTGCAACAGAAACAGCTCTTAATACTGCAGCTTTTAGAAAAGATATCTT
TCTTAGAAGGAGAGAATAATGAACTACAAAGCAGGTTGGACTATTTAACAGAAACCCAGGCCAAGACCGAAGTGGAA
ACCAGAGAGATAGGAGTGGGCTGTGATCTTCTACCCAGCCAAACAGGCAGGACTCGTGAAATTGTGATGCCTTCTAG
GAACTACACCCCATACACAAGAGTCCTGGAGTTAACCATGAAGAAAACTCTGACTTAGGCACTCAGAGGCATACACT
TTTTACAGATGGACAAAAGCTCTGGAACCCTGTGGCTTCAAATCCTTTGGGAAGGGTGACTGTTGTTTCCCCTACAC
ACAGTGTAAGCCGGAATGGGAATCGCTGAGGCTCTGATCCACTTCTAAGACAGGAAGGAAAGTGAAGGCAGAGTGAG
CAGGTAAGAGAGGGATATACAAGGTCACATTTCAGACACCCACTCGGCATACCCTGCCGTACTGCATCATCATTTGT
TTTCTTTGTAGACACTGAAATCCTATCAGGAGGATTCCTTCACAATGTATTTTATTTGCTAGACTTTGGTTGGGAGG
GAAAAGGACATTAATTTGAAGTTTCATGTTATTCATGCCAGGATTGTTTGATAGAGCATGAAGGTTTTGTTTACCCA
TAAAAGTATTAGAGGCAGCGTTTCTCTGATACAGAGAGGCCTGTCCACAAGAAGCATGGGCACCCAGCCAAACTTGA
ACCTGGAAGGGAGGGTTCCCGGCCTGCAGGTGCTCTTTCCTCTTGGTCCCAAGCATCTGTGCAGGGTCGTGGGAGCC
ACACTGAGAGACTTGTGTGGGCCAGACAAGCTTCATTCTGATGCGCTAGTCCCTTGGTTTAATTTGTGCCTTATGCT
TTCATTGGACCAGCTGAAATCACTGTATTTATTCAACTTGTGATTTTTTTTTCTTTCTCACTTTAACTTAAAGAGAA
TTTTATATGTCTTGGAAATTTAATAATTTAGTGTTCTCAGTATCAATTGGTGTTTTTGTTAAACGAATGAATCATCT
GTTCATGCATGCTCTACTTTGATATTATAACCTATGTCACATGTGTTTAATAAATACCATATATTTTGTTCTACTAA
AAAAAT 510 <210> SEQ ID NO 14
<211> Length: 2,497
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 14
>T10377_T2
GGGGGGGCCTTCGCGGTGCAGCTGAGGCTGCAAGTAGCCGGCGCCGTCCCGCGTCGCCCCCGCGCAGGGCGGGCCCC
GCACGCTTATCCTGCCCGGGAGGAACGCCGGCGTCCAGCCCGCTACCGACCGCCGCTGCGGGATGCTGCGCTCCACG
TCCACGGTCACCCTGCTCTCGGGCGGCGCCGCCAGGACGCCCGGGGCGCCCAGCAGGAGGGCACTGCCAAGCCTGGG
GCATCTCTGGAGATTGTGTATCCGAGTTTCAGGAGACCATGGAGATCAGCCTCGTAAAATGCTCGGAGGCAAATGTT
TGCAGACTACGGCTGACCGTACCTCCTGAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAGAAAAGAGCA
GCTTCTTGACCTGAGCAATGGAGAACCTACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAG
ATCAAAATCAGCAGAAAGAAATGGTGGTGTATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAA
GATGTGAGAGCCACTTTGGAAAAGGTGAGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACA
GCTCACCCAGGAACTATCAGTTTCCCATGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCC
TGGATCGTTTTAATGCCATGAACTCAGCCTTGGCATCAGATTCCATTGGCCTGCAGAAAACCCTCGTGGATGTGACT
TTGGAAAACAGCAACATTAAGGATCAAATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGGA
AAAGCAGAGGCAGTTGGAGGTAGCGCAAGTTGAAAACCAGCTGCTAAAAATGAAGGTGGAATCGTCCCAAGAAGCCA
ATGCTGAGGTGATGCGAGAGATGACCAAGAAGCTGTACAGCCAGTATGAGGAGAAGCTGCAGGAAGAACAGAGGAAG
CACAGTGCTGAGAAGGAGGCTCTTTTGGAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGAT
GCAAGCAGCAGAGATCAGCCTAGAGGAGAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAA
AGGAACGTCATCAACTGCAACTTCAACTCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAG
GAAAGGTATCAGCAGTTGGAGGAGGCATCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTG
CCAGCAGAAGAAAGTCAAGCAGATGGTCGAGGAGATTGAATCATTAAAGAAAAAGTTGCAACAGAAACAGCTCTTAA
TACTGCAGCTTTTAGAAAAGATATCTTTCTTAGAAGGAGAGAATAATGAACTACAAAGCAGGTTGGACTATTTAACA
GAAACCCAGGCCAAGACCGAAGTGGAAACCAGAGAGATAGGAGTGGGCTGTGATCTTCTACCCAGCCAAACAGGCAG
GACTCGTGAAATTGTGATGCCTTCTAGGAACTACACCCCATACACAAGAGTCCTGGAGTTAACCATGAAGAAAACTC
TGACTTAGGCACTCAGAGGCATACACTTTTTACAGATGGACAAAAGCTCTGGAACCCTGTGGCTTCAAATCCTTTGG
GAAGGGTGACTGTTGTTTCCCCTACACACAGTGTAAGCCGGAATGGGAATCGCTGAGGCTCTGATCCACTTCTAAGA
CAGGAAGGAAAGTGAAGGCAGAGTGAGCAGGTAAGAGAGGGATATACAAGGTCACATTTCAGACACCCACTCGGCAT
ACCCTGCCGTACTGCATCATCATTTGTTTTCTTTGTAGACACTGAAATCCTATCAGGAGGATTCCTTCACAATGTAT
TTTATTTGCTAGACTTTGGTTGGGAGGGAAAAGGACATTAATTTGAAGTTTCATGTTATTCATGCCAGGATTGTTTG
ATAGAGCATGAAGGTTTTGTTTACCCATAAAAGTATTAGAGGCAGCGTTTCTCTGATACAGAGAGGCCTGTCCACAA
GAAGCATGGGCACCCAGCCAAACTTGAACCTGGAAGGGAGGGTTCCCGGCCTGCAGGTGCTCTTTCCTCTTGGTCCC
AAGCATCTGTGCAGGGTCGTGGGAGCCACACTGAGAGACTTGTGTGGGCCAGACAAGCTTCATTCTGATGCGCTAGT
CCCTTGGTTTAATTTGTGCCTTATGCTTTCATTGGACCAGCTGAAATCACTGTATTTATTCAACTTGTGATTTTTTT
TTCTTTCTCACTTTAACTTAAAGAGAATTTTATATGTCTTGGAAATTTAATAATTTAGTGTTCTCAGTATCAATTGG 511 TGTTTTTGTTAAACGAATGAATCATCTGTTCATGCATGCTCTACTTTGATATTATAACCTATGTCACATGTGTTTAA
TAAATACCATATATTTTGTTCTACTAAAAAAAT
<210> SEQ ID NO 15
<211> Length: 2,328
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 15
>T10377_T5
GGGGGGGCCTTCGCGGTGCAGCTGAGGCTGCAAGTAGCCGGCGCCGTCCCGCGTCGCCCCCGCGCAGGGCGGGCCCC
GCACGCTTATCCTGCCCGGGAGGAACGCCGGCGTCCAGCCCGCTACCGACCGCCGCTGCGGGATGCTGCGCTCCACG
TCCACGGTCACCCTGCTCTCGGGCGGCGCCGCCAGGACGCCCGGGGCGCCCAGCAGGAGGGCAAATGTTTGCAGACT
ACGGCTGACCGTACCTCCTGAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAGAAAAGAGCAGCTTCTTG
ACCTGAGCAATGGAGAACCTACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAGATCAAAAT
CAGCAGAAAGAAATGGTGGTGTATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAAGATGTGAG
AGCCACTTTGGAAAAGGTGAGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACAGCTCACCC
AGGAACTATCAGTTTCCCATGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCCTGGATCGT
TTTAATGCCATGAACTCAGCCTTGGCATCAGATTCCATTGGCCTGCAGAAAACCCTCGTGGATGTGACTTTGGAAAA
CAGCAACATTAAGGATCAAATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGGAAAAGCAGA
GGCAGTTGGAGGTAGCGCAAGTTGAAAACCAGCTGCTAAAAATGAAGGTGGAATCGTCCCAAGAAGCCAATGCTGAG
GTGATGCGAGAGATGACCAAGAAGCTGTACAGCCAGTATGAGGAGAAGCTGCAGGAAGAACAGAGGAAGCACAGTGC
TGAGAAGGAGGCTCTTTTGGAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGATGCAAGCAG
CAGAGATCAGCCTAGAGGAGAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAAAGGAACGT
CATCAACTGCAACTTCAACTCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAGGAAAGGTA
TCAGCAGTTGGAGGAGGCATCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTGCCAGCAGA
AGAAAGTCAAGCAGATGGTCGAGGAGAATAATGAACTACAAAGCAGGTTGGACTATTTAACAGAAACCCAGGCCAAG
ACCGAAGTGGAAACCAGAGAGATAGGAGTGGGCTGTGATCTTCTACCCAGCCAAACAGGCAGGACTCGTGAAATTGT
GATGCCTTCTAGGAACTACACCCCATACACAAGAGTCCTGGAGTTAACCATGAAGAAAACTCTGACTTAGGCACTCA
GAGGCATACACTTTTTACAGATGGACAAAAGCTCTGGAACCCTGTGGCTTCAAATCCTTTGGGAAGGGTGACTGTTG
TTTCCCCTACACACAGTGTAAGCCGGAATGGGAATCGCTGAGGCTCTGATCCACTTCTAAGACAGGAAGGAAAGTGA
AGGCAGAGTGAGCAGGTAAGAGAGGGATATACAAGGTCACATTTCAGACACCCACTCGGCATACCCTGCCGTACTGC
ATCATCATTTGTTTTCTTTGTAGACACTGAAATCCTATCAGGAGGATTCCTTCACAATGTATTTTATTTGCTAGACT
TTGGTTGGGAGGGAAAAGGACATTAATTTGAAGTTTCATGTTATTCATGCCAGGATTGTTTGATAGAGCATGAAGGT
TTTGTTTACCCATAAAAGTATTAGAGGCAGCGTTTCTCTGATACAGAGAGGCCTGTCCACAAGAAGCATGGGCACCC
AGCCAAACTTGAACCTGGAAGGGAGGGTTCCCGGCCTGCAGGTGCTCTTTCCTCTTGGTCCCAAGCATCTGTGCAGG
GTCGTGGGAGCCACACTGAGAGACTTGTGTGGGCCAGACAAGCTTCATTCTGATGCGCTAGTCCCTTGGTTTAATTT
GTGCCTTATGCTTTCATTGGACCAGCTGAAATCACTGTATTTATTCAACTTGTGATTTTTTTTTCTTTCTCACTTTA 512 ACTTAAAGAGAATTTTATATGTCTTGGAAATTTAATAATTTAGTGTTCTCAGTATCAATTGGTGTTTTTGTTAAACG
AATGAATCATCTGTTCATGCATGCTCTACTTTGATATTATAACCTATGTCACATGTGTTTAATAAATACCATATATT
TTGTTCTACTAAAAAAAT
<210> SEQ ID NO 16
<211> Length: 2,311
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 16
>T10377_T6
GGGGGGGCCTTCGCGGTGCAGCTGAGGCTGCAAGTAGCCGGCGCCGTCCCGCGTCGCCCCCGCGCAGGGCGGGCCCC
GCACGCTTATCCTGCCCGGGAGGAACGCCGGCGTCCAGCCCGCTACCGACCGCCGCTGCGGGATGCTGCGCTCCACG
TCCACGGTCACCCTGCTCTCGGGCGGCGCCGCCAGGACGCCCGGGGCGCCCAGCAGGAGGGCAAATGTTTGCAGACT
ACGGCTGACCGTACCTCCTGAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAGAAAAGAGCAGCTTCTTG
ACCTGAGCAATGGAGAACCTACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAGATCAAAAT
CAGCAGAAAGAAATGGTGGTGTATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAAGATGTGAG
AGCCACTTTGGAAAAGGTGAGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACAGCTCACCC
AGGAACTATCAGTTTCCCATGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCCTGGATCGT
TTTAATGCCATGAACTCAGCCTTGGCATCAGATTCCATTGGCCTGCAGAAAACCCTCGTGGATGTGACTTTGGAAAA
CAGCAACATTAAGGATCAAATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGGAAAAGCAGA
GGCAGTTGGAGGTAGCGCAAGTTGAAAACCAGCTGCTAAAAATGAAGGTGGAATCGTCCCAAGAAGCCAATGCTGAG
GTGATGCGAGAGATGACCAAGAAGCTGTACAGCCAGTATGAGGAGAAGCTGCAGGAAGAACAGAGGAAGCACAGTGC
TGAGAAGGAGGCTCTTTTGGAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGATGCAAGCAG
CAGAGATCAGCCTAGAGGAGAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAAAGGAACGT
CATCAACTGCAACTTCAACTCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAGGAAAGGTA
TCAGCAGTTGGAGGAGGCATCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTGCCAGCAGA
AGAAAGTCAAGCAGATGGTCGAGGAGATTGAATCATTAAAGAAAAAGTTGCAACAGAAACAGCTCTTAATACTGCAG
CTTTTAGAAAAGATATCTTTCTTAGAAGGAGAGCCAAACAGGCAGGACTCGTGAAATTGTGATGCCTTCTAGGAACT
ACACCCCATACACAAGAGTCCTGGAGTTAACCATGAAGAAAACTCTGACTTAGGCACTCAGAGGCATACACTTTTTA
CAGATGGACAAAAGCTCTGGAACCCTGTGGCTTCAAATCCTTTGGGAAGGGTGACTGTTGTTTCCCCTACACACAGT
GTAAGCCGGAATGGGAATCGCTGAGGCTCTGATCCACTTCTAAGACAGGAAGGAAAGTGAAGGCAGAGTGAGCAGGT
AAGAGAGGGATATACAAGGTCACATTTCAGACACCCACTCGGCATACCCTGCCGTACTGCATCATCATTTGTTTTCT
TTGTAGACACTGAAATCCTATCAGGAGGATTCCTTCACAATGTATTTTATTTGCTAGACTTTGGTTGGGAGGGAAAA
GGACATTAATTTGAAGTTTCATGTTATTCATGCCAGGATTGTTTGATAGAGCATGAAGGTTTTGTTTACCCATAAAA
GTATTAGAGGCAGCGTTTCTCTGATACAGAGAGGCCTGTCCACAAGAAGCATGGGCACCCAGCCAAACTTGAACCTG
GAAGGGAGGGTTCCCGGCCTGCAGGTGCTCTTTCCTCTTGGTCCCAAGCATCTGTGCAGGGTCGTGGGAGCCACACT
GAGAGACTTGTGTGGGCCAGACAAGCTTCATTCTGATGCGCTAGTCCCTTGGTTTAATTTGTGCCTTATGCTTTCAT 513 TGGACCAGCTGAAATCACTGTATTTATTCAACTTGTGATTTTTTTTTCTTTCTCACTTTAACTTAAAGAGAATTTTA
TATGTCTTGGAAATTTAATAATTTAGTGTTCTCAGTATCAATTGGTGTTTTTGTTAAACGAATGAATCATCTGTTCA
TGCATGCTCTACTTTGATATTATAACCTATGTCACATGTGTTTAATAAATACCATATATTTTGTTCTACTAAAAAAA
T
<210> SEQ ID NO 17
<211> Length: 1418
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 17
>T10377_T7
GGGGGGGCCTTCGCGGTGCAGCTGAGGCTGCAAGTAGCCGGCGCCGTCCCGCGTCGCCCCCGCGCAGGGCGGGCCCC
GCACGCTTATCCTGCCCGGGAGGAACGCCGGCGTCCAGCCCGCTACCGACCGCCGCTGCGGGATGCTGCGCTCCACG
TCCACGGTCACCCTGCTCTCGGGCGGCGCCGCCAGGACGCCCGGGGCGCCCAGCAGGAGGGCAAATGTTTGCAGACT
ACGGCTGACCGTACCTCCTGAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAGAAAAGAGCAGCTTCTTG
ACCTGAGCAATGGAGAACCTACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAGATCAAAAT
CAGCAGAAAGAAATGGTGGTGTATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAAGATGTGAG
AGCCACTTTGGAAAAGGTGAGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACAGCTCACCC
AGGAACTATCAGTTTCCCATGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCCTGGATCGT
TTTAATGCCATGAACTCAGCCTTGGCATCAGATTCCATTGGCCTGCAGAAAACCCTCGTGGATGTGACTTTGGAAAA
CAGCAACATTAAGGATCAAATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGGAAAAGCAGA
GGCAGTTGGAGGTAGCGCAAGTTGAAAACCAGCTGCTAAAAATGAAGGTGGAATCGTCCCAAGAAGCCAATGCTGAG
GTGATGCGAGAGATGACCAAGAAGCTGTACAGCCAGTATGAGGAGAAGCTGCAGGAAGAACAGAGGAAGCACAGTGC
TGAGAAGGAGGCTCTTTTGGAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGATGCAAGCAG
CAGAGATCAGCCTAGAGGAGAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAAAGGAACGT
CATCAACTGCAACTTCAACTCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAGGAAAGGTA
TCAGCAGTTGGAGGAGGCATCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTGCCAGCAGA
AGAAAGTCAAGCAGATGGTCGAGGAGATCATGTCGCACGAGCTCTTCTCCAGATTTAGTCTCCGGCTCTTTGGAAGA
TGATAAGTTGGTAGCCTGCTCTGGGTTGGAAGCGATTCCTTTATTGTTCGTGATTAGAAGAACACTTGTACACTCTC
TGCTGGGAAGAGGTGGTATTTATCTATGATGA
<210> SEQ ID NO 18
<211> Length: 1,027
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 18 514 >Z24874_PEA_2_T10
GTTGGCCCTGACCTCGTTGGAAAACGAAGCTCCCCGCAGGGTCCCGGCCTCTAGGGCTGCTGTGCGGGCGGGGGTGG
CCTGGAGCTATTTCCATTCGGCGGCGGGAACAGGTGCCGGCGCCTCCGCCCCATCCCCAGGGGCCGCCTCCCCCGGG
GCGGCCTCCAGGCTGCCGAGACCTATAAAGGCGCCAGGTTTTCTCAATGAAGCCGGGACGCACTCCGGAGCGCACTG
CGTGGTCGCACCCTACCCGGGCTGCCTTGGAAGTCGTCCCCGCCGCCCCTCCGCACCGGCATGAAGCTCATCGTGGG
CATCGGAGGCATGACCAACGGCGGCAAGACCACGCTGACCAACAGCCTGCTCAGAGCCCTGCCCAACTGCTGCGTGA
TCCATCAGGATGACTTCTTCAAGCCCCAAGACCAAATAGCAGTTGGGGAAGACGGCTTCAAACAGTGGGACGTGCTG
GAGTCTCTGGACATGGAGGCCATGCTGGACACCGTGCAGGCCTGGCTGAGCAGCCCGCAGAAGTTTGCCCGTGCCCA
CGGGGTCAGCGTCCAGCCAGAGGCCTCGGACACCCACATCCTCCTCCTGGAAGGCTTCCTGCTCTACAGCTACAAGC
CCCTGGTGGACTTGTACAGCCGCCGGTACTTCCTGACCGTCCCGTATGAAGAGTGCAAGTGGAGGAGAAGTCTACCT
GGACGGCATGAAGTCCCGAGAGGAGCTCTTCCGTGAAGTCCTGGAAGACATTCAGAACTCGCTGCTGAACCGCTCCC
AGGAATCAGCCCCCTCCCCGGCTCGCCCAGCCAGGACACAGGGACCCGGACGCGGATGCGGCCACAGAACGGCCAGG
CCTGCAGCGTCCCAGCAGGACAGCATGTGAGCGTTTCCCTATGGGGGTGTCTGTACGTAGGAGAGTGGAGGCCCCAC
TCCCAGTTGGGCGTCCCGGAGCTCAGGGACTGAGCCCCAAGACGCCTCTGTAACCTCGCTGCAGCTTCAGTAGTAAA
CTGGGTCCTGTTTTTTTAACTGTTGG
<210> SEQ ID NO 19
<211> Length: 955
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 19
>Z24874_PEA_2_T11
GTTGGCCCTGACCTCGTTGGAAAACGAAGCTCCCCGCAGGGTCCCGGCCTCTAGGGCTGCTGTGCGGGCGGGGGTGG
CCTGGAGCTATTTCCATTCGGCGGCGGGAACAGGTGCCGGCGCCTCCGCCCCATCCCCAGGGGCCGCCTCCCCCGGG
GCGGCCTCCAGGCTGCCGAGACCTATAAAGGCGCCAGGTTTTCTCAATGAAGCCGGGACGCACTCCGGAGCGCACTG
CGTGGTCGCACCCTACCCGGGCTGCCTTGGAAGTCGTCCCCGCCGCCCCTCCGCACCGGCATGAAGCTCATCGTGGG
CATCGGAGGCATGACCAACGGCGGCAAGACCACGCTGACCAACAGCCTGCTCAGAGCCCTGCCCAACTGCTGCGTGA
TCCATCAGGATGACTTCTTCAAGCCCCAAGACCAAATAGCAGTTGGGGAAGACGGCTTCAAACAGTGGGACGTGCTG
GAGTCTCTGGACATGGAGGCCATGCTGGACACCGTGCAGGCCTGGCTGAGCAGCCCGCAGAAGTTTGCCCGTGCCCA
CGGGGTCAGCGTCCAGCCAGAGGCCTCGGACACCCACATCCTCCTCCTGGAAGGCTTCCTGCTCTACAGCTACAATC
TACCTGGACGGCATGAAGTCCCGAGAGGAGCTCTTCCGTGAAGTCCTGGAAGACATTCAGAACTCGCTGCTGAACCG
CTCCCAGGAATCAGCCCCCTCCCCGGCTCGCCCAGCCAGGACACAGGGACCCGGACGCGGATGCGGCCACAGAACGG
CCAGGCCTGCAGCGTCCCAGCAGGACAGCATGTGAGCGTTTCCCTATGGGGGTGTCTGTACGTAGGAGAGTGGAGGC
CCCACTCCCAGTTGGGCGTCCCGGAGCTCAGGGACTGAGCCCCAAGACGCCTCTGTAACCTCGCTGCAGCTTCAGTA
GTAAACTGGGTCCTGTTTTTTTAACTGTTGG
<210> SEQ ID NO 20 515 <211> Length: 986
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 20
>HUMCDDANF_T3
GGTTGGATTCCTGGGAGCTTCATCACATTTGGTTCTCAGCTGACTTTATATACTAAAAAATAACTTCCTTTCGCCTG
ACCATGGAGAGGGACTGCCAGGGGTGAAGGCAGCCCTGTCTGAGGCCAGAGGTCTGCCCACGTGGCGGATGAGGCAG
GTGTGAGGCCAGCTTGAGCATCTGGATCCATTTGTCTCGGGCTGCTGGCTGCCTGCCATTTCCTCCTCTCCACCCTT
ATTTGGAGGCCCTGACAGCTGAGCCACAAACAAACCAGGGGAGCTGGGCACCAGCCAAGCGTCACCCTCTGTTTCCC
CGCACGGGTACCAGCGTCGAGGAGAAAGAATCCTGAGGCACGGCGAATTTGCTGGACCATTTGGAAGAAAAGATGCC
TTTAGAAGATGAGGTCGTGCCCCCACAAGTGCTCAGTGAGCCGAATGAAGAAGCGGGGGCTGCTCTCAGCCCCCTCC
CTGAGGTGCCTCCCTGGACCGGGGAAGTCAGCCCAGCCCAGAGAGATGGAGGTGCCCTCGGGCGGGGCCCCTGGGAC
TCCTCTGATCGATCTGCCCTCCTAAAAAGCAAGCTGAGGGCGCTGCTCACTGCCCCTCGGAGCCTGCGGAGATCCAG
CTGCTTCGGGGGCAGGATGGACAGGATTGGAGCCCAGAGCGGACTGGGCTGTAACAGCTTCCGGTACTGAAGATAAC
AGCCAGGGAGGACAAGCAGGGCTGGGCCTAGGGACAGACTGCAAGAGGCTCCTGTCCCCTGGGGTCTCTGCTGCATT
TGTGTCATCTTGTTGCCATGGAGTTGTGATCATCCCATCTAAGCTGCAGCTTCCTGTCAACACTTCTCACATCTTAT
GCTAACTGTAGATAAAGTGGTTTGATGGTGACTTCCTCGCCTCTCCCACCCCATGCATTAAATTTTAAGGTAGAACC
TCACCTGTTACTGAAAGTGGTTTGAAAGTGAATAAACTTCAGCACCATGGACAGAAGACAAA
<210> SEQ ID NO 21
<211> Length: 760
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 21
>HUMCDDANF_T4
CtGGGAGACAGGGACAGACGTAGGCCAAGAGAGGGGAACCAGAGAGGAACCAGAGGGGAGAGACAGAGCAGCAAGCA
GTGGATTGCTCCTTGACGACGCCAGCATGAGCTCCTTCTCCACCACCACCAATTTGCTGGACCATTTGGAAGAAAAG
ATGCCTTTAGAAGATGAGGTCGTGCCCCCACAAGTGCTCAGTGAGCCGAATGAAGAAGCGGGGGCTGCTCTCAGCCC
CCTCCCTGAGGTGCCTCCCTGGACCGGGGAAGTCAGCCCAGCCCAGAGAGATGGAGGTGCCCTCGGGCGGGGCCCCT
GGGACTCCTCTGATCGATCTGCCCTCCTAAAAAGCAAGCTGAGGGCGCTGCTCACTGCCCCTCGGAGCCTGCGGAGA
TCCAGCTGCTTCGGGGGCAGGATGGACAGGATTGGAGCCCAGAGCGGACTGGGCTGTAACAGCTTCCGGTACTGAAG
ATAACAGCCAGGGAGGACAAGCAGGGCTGGGCCTAGGGACAGACTGCAAGAGGCTCCTGTCCCCTGGGGTCTCTGCT
GCATTTGTGTCATCTTGTTGCCATGGAGTTGTGATCATCCCATCTAAGCTGCAGCTTCCTGTCAACACTTCTCACAT
CTTATGCTAACTGTAGATAAAGTGGTTTGATGGTGACTTCCTCGCCTCTCCCACCCCATGCATTAAATTTTAAGGTA
GAACCTCACCTGTTACTGAAAGTGGTTTGAAAGTGAATAAACTTCAGCACCATGGACAGAAGACAAA 516 <210> SEQ ID NO 22
<231> Length: 892
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 22
>HUMTROPIA_PEA_2_T10
TCTCAGTGTCCTCGGGGAGTCTCAAGCAGCCCGGAGGAGACTGACGGTCCCTGGGACCCTGAAGGTCACCCGGGCGG
CCCCCTCACTGACCCTCCAAACGCCCCTGTCCTCGCCCTGCCTCCTGCCATTCCCGGCCTGAGTCTCAGCATGGCGG
ATGGGAGCAGCGATGCGGTGAGAGCAGCGGGCTAAGGCGTGGCTGGGACCCCCAGGGCCAGGGCTAGGGAACCTCGC
CCTGCACCAGCCCCAATCAGACGCCGCTCCTCCAACTACCGCGCTTATGCCACGGAGCCGCACGCCAAGAAAAAATC
TAAGATCTCCGCCTCGAGAAAATTGCAGCTGAAGACTCTGCTGCTGCAGATTGCAAAGCAAGAGCTGGAGCGAGAGG
CGGAGGAGCGGCGCGGAGAGAAGGGGCGCGCTCTGAGCACCCGCTGCCAGCCGCTGGAGTTGGCCGGGCTGGGCTTC
GCGGAGCTGCAGGACTTGTGCCGACAGCTCCACGCCCGTGTGGACAAGGTGGATGAAGAGAGATACGACATAGAGGC
AAAAGTCACCAAGAACATCACGGAGATTGCAGATCTGACTCAGAAGATCTTTGACCTTCGAGGCAAGTTTAAGCGGC
CCACCCTGCGGAGAGTGAGGATCTCTGCAGATGCCATGATGCAGGCGCTGCTGGGGGCCCGGGCTAAGGAGTCCCTG
GACCTGCGGGCCCACCTCAAGCAGGTGAAGAAGGAGGACACCGAGAAGGAAAACCGGGAGGTGGGAGACTGGCGCAA
GAACATCGATGCACTGAGTGGAATGGAGGGCCGCAAGAAAAAGTTTGAGAGCTGAGCCTTCCTGCCTACTGCCCCTG
CCCTGAGGAGGGCCCTGAGGAATAAAGCTTCTCTCTGAGCTGAAA
<210> SEQ ID NO 23
<211> Length: 763
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 23
>HUMTROPIA_PEA_2_T15
TCTCAGTGTCCTCGGGGAGTCTCAAGCAGCCCGGAGGAGACTGACGGTCCCTGGGACCCTGAAGGTCACCCGGGCGG
CCCCCTCACTGACCCTCCAAACGCCCCTGTCCTCGCCCTGCCTCCTGCCATTCCCGGCCTGAGTCTCAGCATGGCGG
ATGGGAGCAGCGATGCGAAAAAATCTAAGATCTCCGCCTCGAGAAAATTGCAGCTGAAGACTCTGCTGCTGCAGATT
GCAAAGCAAGAGCTGGAGCGAGAGGCGGAGGAGCGGCGCGGAGAGAAGGGGCGCGCTCTGAGCACCCGCTGCCAGCC
GCTGGAGTTGGCCGGGCTGGGCTTCGCGGAGCTGCAGGACTTGTGCCGACAGCTCCACGCCCGTGTGGACAAGGTGG
ATGAAGAGAGATACGACATAGAGGCAAAAGTCACCAAGAACATCACGGAGATTGCAGATCTGACTCAGAAGATCTTT
GACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGATCTCTGCAGATGCCATGATGCAGGCGCTGCT
GGGGGCCCGGGCTAAGGAGTCCCTGGACCTGCGGGCCCACCTCAAGCAGGTGAAGAAGGAGGACACCGAGAAGGAAA
ACCGGGAGGTGGGAGACTGGCGCAAGAACATCGATGCACTGAGTGGAATGGAGGGCCGCAAGAAAAAGTTTGAGAGC
TGAGCCTTCCTGCCTACTGCCCCTGCCCTGAGGAGGGCCCTGAGGAATAAAGCTTCTCTCTGAGCTGAAA 517 <210> SEQ ID NO 24
<211> Length: 1,381
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 24
>HUMTROPIA_PEA_2__T3
TCTCAGTGTCCTCGGGGAGTCTCAAGCAGCCCGGAGGAGACTGACGGTCCCTGGGACCCTGAAGGTCACCCGGGCGG
CCCCCTCACTGACCCTCCAAACGCCCCTGTCCTCGCCCTGCCTCCTGCCATTCCCGGCCTGAGTCTCAGCATGGCGG
ATGGGAGCAGCGATGCGGCTAGGGAACCTCGCCCTGCACCAGCCCCAATCAGACGCCGCTCCTCCAACTACCGCGCT
TATGCCACGGAGCCGCACGCCAAGAAAAAATCTAAGATCTCCGCCTCGAGAAAATTGCAGCTGAAGACTCTGCTGCT
GCAGATTGCAAAGCAAGAGCTGGAGCGAGAGGCGGAGGAGCGGCGCGGAGAGAAGGGGCGCGCTCTGAGCACCCGCT
GCCAGCCGCTGGAGTTGGCCGGGCTGGGCTTCGCGGAGCTGCAGGACTTGTGCCGACAGCTCCACGCCCGTGTGGAC
AAGGTGGATGAAGAGAGATACGACATAGAGGCAAAAGTCACCAAGAACATCACGGAGGTGGGACGCATGGGCAGCTC
GGGTACCTTCGGGGTAGGGTGAGATGGCTGGGACTTGGTCTCTGCCTGACCCCTTGCAGCTGCTTTTGGCTGCACAT
CCCAGGAGACCCAGGACAACTGTGAGCCTGGCAGGGCTGGGGCAGAAGGATGAGTACAATATAGTCAAGGAAAGCTG
TTCTAGGCAGAGGGAACAGCACATGCAAGGCCATGGGTTGGGAAACAGAAAATAAGTTAGTGAACATGCTCAGGGCA
TCACATGTTGGTAAATTAGCTCAGGCACTGGCCAGGGAATTGTGATTTGCATGTAGCTGGACCAGGTTATGCCAGTG
GTTTTGAGAGGTGAGGCTGGAGCATATGAGGAGGGGGATTCAGTTCCAGGATTAGAAGCCTAGACTGGGAGCCTAAG
CCGGGAAGAGACTGGTAAGGCCTCGGTACTGGAAGACGAGATAAGGAGAATAAAAAAGGAGTGTAGGATGGAGGAGT
TGGGTGTGCGGGAAATGGAAGGAGAAGTACCCACCCCCTCGTGTGCCCCCAGATTGCAGATCTGACTCAGAAGATCT
TTGACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGATCTCTGCAGATGCCATGATGCAGGCGCTG
CTGGGGGCCCGGGCTAAGGAGTCCCTGGACCTGCGGGCCCACCTCAAGCAGGTGAAGAAGGAGGACACCGAGAAGGA
AAACCGGGAGGTGGGAGACTGGCGCAAGAACATCGATGCACTGAGTGGAATGGAGGGCCGCAAGAAAAAGTTTGAGA
GCTGAGCCTTCCTGCCTACTGCCCCTGCCCTGAGGAGGGCCCTGAGGAATAAAGCTTCTCTCTGAGCTGAAA
<210> SEQ ID NO 25
<211> Length: 1,252
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 25
>HUMTROPIA_PEA_2_T7
TCTCAGTGTCCTCGGGGAGTCTCAAGCAGCCCGGAGGAGACTGACGGTCCCTGGGACCCTGAAGGTCACCCGGGCGG
CCCCCTCACTGACCCTCCAAACGCCCCTGTCCTCGCCCTGCCTCCTGCCATTCCCGGCCTGAGTCTCAGCATGGCGG
ATGGGAGCAGCGATGCGGCTAGGGAACCTCGCCCTGCACCAGCCCCAATCAGACGCCGCTCCTCCAACTACCGCGCT
TATGCCACGGAGCCGCACGCCAAGGTGGGACGGGGCTTCCTGGGGGCAGAGTACAGGCGCCGGAGGGATCCAAGACC
CTGGGAGTGGGGGGAGGAGCCAGGGCTGCGAAGGGGGCGGGGACTACGCGGAGGGGCTTCAGGGGCGGAGTTTTGCA 518 GAGGGTCATGCTCGGATTGGTGACAGCAGCCTGCGGGCGGAACTCCGTTGCCCTCGGACTTGCTTAGGGATAGATGG
GAAGTGCCTATCCAAAGGAAGAGACCCAGATTGGTGGATGGGAATGAGGGGCGTGGCCTCCCGTAGACTCAGGGCTC
AAGTTGGACGTGGGCCCAAATCTGGACCGGCTGGGTTTGCTGGGGGTGTCTTGAGGTCCCCTCCACCGTCGTCTCCG
AATCCCCCTCCATGATCCTTCCTTGCTCCATCTCACCCTGGCAGAAAAAATCTAAGATCTCCGCCTCGAGAAAATTG
CAGCTGAAGACTCTGCTGCTGCAGATTGCAAAGCAAGAGCTGGAGCGAGAGGCGGAGGAGCGGCGCGGAGAGAAGGG
GCGCGCTCTGAGCACCCGCTGCCAGCCGCTGGAGTTGGCCGGGCTGGGCTTCGCGGAGCTGCAGGACTTGTGCCGAC
AGCTCCACGCCCGTGTGGACAAGGTGGATGAAGAGAGATACGACATAGAGGCAAAAGTCACCAAGAACATCACGGAG
ATTGCAGATCTGACTCAGAAGATCTTTGACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGATCTC
TGCAGATGCCATGATGCAGGCGCTGCTGGGGGCCCGGGCTAAGGAGTCCCTGGACCTGCGGGCCCACCTCAAGCAGG
TGAAGAAGGAGGACACCGAGAAGGAAAACCGGGAGGTGGGAGACTGGCGCAAGAACATCGATGCACTGAGTGGAATG
GAGGGCCGCAAGAAAAAGTTTGAGAGCTGAGCCTTCCTGCCTACTGCCCCTGCCCTGAGGAGGGCCCTGAGGAATAA
AGCTTCTCTCTGAGCTGAAA
<210> SEQ ID NO 26
<211> Length: 2,820
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 26
>HUMSMCK_T5
TTCCATGCTCTTTAAAAGCCTTATAATTTTCTGGATCTGGGAGCTGGGCTATTTCAGGGTCAATGGATTTATTTCAG
TTGGTGCCTGAACTGACTTGAAACAAGTGTGTGTGGAAAAGAGCTATTTTGAGAAGGAATAAACCGAGACTGCCCTG
ATGATAGAATATGCAAGCTGGTGGGTCTTGACTCCTTAAAGGATTATGAAATTAATTTGATTGGTCCCAATCTTTAT
ATAACCACCCCAATCAGGAAACTTCCCATCCCGCCAAAAGGCCCCCTCACGTGCTCTCCCTGTCAGTACCCCATGCA
AAGGTAAAATAGATGATATTTTTAAACATGGGTCGTGTTTAAAAGAAATGGAAACTCCTTCAGAGAATGAAGGAGAA
CCACACTGGGTAGAAGGTTATTCCTGGGGCTCCACCCCTTGCTCCATCAAGTCCTCTGAGCATGAGCTGGGCTCTGA
GAAGGAAGAGACAGGAACCAATTGGTCATGTCCACGTGGCCTCAGAAGCTGAGTACGTGACGGTCACCAGATGCCTA
GGCAGGCTCCCTTGAAATGGCAGGGCTGCTGTCCAAAATCCTGCTGGGTCATTGCTATTTACAGGCAGCCTTCCCGG
CGTGCGGTGGATATCCCAAGCGGGGCTATTTTTAAGCAGGGCTATGGCCTGCCGTGGGTTAAGCTGGTGTGGACAGA
AAGCGAGATGATCTAGCCATCTACTGCAGGGGGCCTGATCTTGAACAGAAACCTGACTGTAATTGTCCCTGGATCCA
GGTCCCAGACAAAGACGCTGGAAGGAGGTCCCTCCAGCCCCTGGCTCAGGGCCCGGTCAGCTGCTGGAGCCAGGCAG
CTTGAGACATCCTCCTCTCCGACCTTGGCTTGAGGGGTTCATCCTCCAGAGCTCACCAGGGCCCCAAGGCTGGTACA
CCTGAGAGAAGAGAGAAACAAATCCCCCAACAGATGTGCAATTTCACCTGCTGGCCCTTCCATTCTGAGATCCAGAG
CCCTGGCAAAGGAGCCTCCAGGACCAGGCCTGGGAAGCAAGACTGGCTCCGCCTTTTACGTTTCAGAGAAAGGGCAG
GTGCTATAAAGGGCCCAGCGCCCACGGGCCTGCCTTCAAGGGTACAGCTGTGGGGGCCGGTGCGCCCGGAGGTCTAC
GCTGGGATTGGTGAGGTCCTCTGGCCCCGCCCCGCCAGGGAGGATTTCCAGGCCGGCCCGACCAGCTCGCCCTGCAT
ACACTTCTTGGCTGTGTGCGCTCAGCAGGACGTGGGAGGCTCCGGCTTCAAGACACTCATCCAAGAGGAAGGATGGC
CAGTATCTTTTCTAAGTTGCTAACTGGCCGCAATGCTTCTCTGCTGTTTGCTACCATGGGCACCAGTGTCCTGACCA 519 CCGGGTACCTGCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGGGAGCAGCCTAGGCTATTTCCTCCAAGCGCAGAC
TACCCAGACCTGCGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCCCCGCCATTTATGCCAAGCTTCGCAACAA
GGTGACACCCAACGGCTACACGCTGGACCAGTGCATCCAGACTGGAGTGGACAACCCTGGCCACCCCTTCATAAAGA
CTGTGGGCATGGTGGCTGGTGACGAGGAGTCCTATGAGGTGTTTGCTGACCTTTTTGACCCCGTCATCAAACTAAGA
CACAACGGCTATGACCCCAGGGTGATGAAGCACACAACGGATCTGGATGCATCAAAGATCACCCAAGGGCAGTTCGA
CGAGCATTACGTGCTGTCTTCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAGCCTGCCTCCAGCCTGCACCC
GGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGGGGGACCTGGCTGGCCGCTAC
TACAAGCTGTCCGAGATGACGGAGCAGGACCAGCAGCGGCTCATCGATGACCACTTTCTGTTTGATAAGCCAGTGTC
CCCTTTATTAACATGTGCTGGGATGGCCCGTGACTGGCCAGATGCCAGGGGAATCTGGCATAATTATGATAAGACAT
TTCTCATCTGGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAGGCAATATGAAACGAGTATTT
GAGCGATTCTGTCGTGGACTAAAAGAAGTAGAACGGTTAATCCAAGAACGAGGCTGGGAGTTCATGTGGAATGAGCG
CCTAGGATACATTTTGACCTGTCCTTCGAACCTTGGAACAGGACTACGAGCTGGTGTCCACGTTAGGATCCCAAAGC
TCAGCAAGGACCCACGCTTTTCTAAGATCCTGGAAAACCTAAGACTCCAGAAGCGTGGCACAGGTGGTGTGGACACT
GCCGCGGTCGCAGATGTGTACGACATTTCCAACATAGATAGAATTGGTCGATCAGAGGTAACGTCTCTCTCACTTTC
CTAACATGAACTAACAAAATCAGCCTAAGAGAGAATAGAGAAAAGCAAACAGCCTAGCCGTTTTCACAAAATTCGAG
ACCTCCTCTTCGCCCATTGAGTCCTGAGTTATGTTAGCTTTTCATTCTGTAACATTATTCTTCCATGGGAAATAACT
GCATAAAGGGAAACATAATGTGAGCTGAGAATTTATAGGCAAGTATAGGAATTCACAGTGGGACTGTTGTCACCGAC
CTGCCATGAGAGCTATTCCAACAATCCTCAGCGAGCAGGAGCTCTGTTATGCTAAAGGACTGCAGTTTTTTTATTAC
TGTAAAGTCAGAACATCTATGCTATCCCTCTGAGGGTGGCAAAATAGT
<210> SEQ ID NO 27
<211> Length: 2,448
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 27
>HUMSMCK_T6
TTCCATGCTCTTTAAAAGCCTTATAATTTTCTGGATCTGGGAGCTGGGCTATTTCAGGGTCAATGGATTTATTTCAG
TTGGTGCCTGAACTGACTTGAAACAAGTGTGTGTGGAAAAGAGCTATTTTGAGAAGGAATAAACCGAGACTGCCCTG
ATGATAGAATATGCAAGCTGGTGGGTCTTGACTCCTTAAAGGATTATGAAATTAATTTGATTGGTCCCAATCTTTAT
ATAACCACCCCAATCAGGAAACTTCCCATCCCGCCAAAAGGCCCCCTCACGTGCTCTCCCTGTCAGTACCCCATGCA
AAGGTAAAATAGATGATATTTTTAAACATGGGTCGTGTTTAAAAGAAATGGAAACTCCTTCAGAGAATGAAGGAGAA
CCACACTGGGTAGAAGGTTATTCCTGGGGCTCCACCCCTTGCTCCATCAAGTCCTCTGAGCATGAGCTGGGCTCTGA
GAAGGAAGAGACAGGAACCAATTGGTCATGTCCACGTGGCCTCAGAAGCTGAGTACGTGACGGTCACCAGATGCCTA
GGCAGGCTCCCTTGAAATGGCAGGGCTGCTGTCCAAAATCCTGCTGGGTCATTGCTATTTACAGGCAGCCTTCCCGG
CGTGCGGTGGATATCCCAAGCGGGGCTATTTTTAAGCAGGGCTATGGCCTGCCGTGGGTTAAGCTGGTGTGGACAGA
AAGCGAGATGATCTAGCCATCTACTGCAGGGGGCCTGATCTTGAACAGAAACCTGACTGTAATTGTCCCTGGATCCA
GGTCCCAGACAAAGACGCTGGAAGGAGGTCCCTCCAGCCCCTGGCTCAGGGCCCGGTCAGCTGCTGGAGCCAGGCAG 520 CTTGAGACATCCTCCTCTCCGACCTTGGCTTGAGGGGTTCATCCTCCAGAGCTCACCAGGGCCCCAAGGCTGGTACA
CCTGAGAGAAGAGAGAAACAAATCCCCCAACAGATGTGCAATTTCACCTGCTGGCCCTTCCATTCTGAGATCCAGAG
CCCTGGCAAAGGAGCCTCCAGGACCAGGCCTGGGAAGCAAGACTGGCTCCGCCTTTTACGTTTCAGAGAAAGGGCAG
GTGCTATAAAGGGCCCAGCGCCCACGGGCCTGCCTTCAAGGGTACAGCTGTGGGGGCCGGTGCGCCCGGAGGTCTAC
GCTGGGATTGGTGAGGTCCTCTGGCCCCGCCCCGCCAGGGAGGATTTCCAGGCCGGCCCGACCAGCTCGCCCTGCAT
ACACTTCTTGGCTGTGTGCGCTCAGCAGGACGTGGGAGGCTCCGGCTTCAAGACACTCATCCAAGAGGAAGGATGGC
CAGTATCTTTTCTAAGTTGCTAACTGGCCGCAATGCTTCTCTGCTGTTTGCTACCATGGGCACCAGTGTCCTGACCA
CCGGGTACCTGCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGGGAGCAGCCTAGGCTATTTCCTCCAAGCGCAGAC
TACCCAGACCTGCGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCCCCGCCATTTATGCCAAGCTTCGCAACAA
GGTGACACCCAACGGCTACACGCTGGACCAGTGCATCCAGACTGGAGTGGACAACCCTGGCCACCCCTTCATAAAGA
CTGTGGGCATGGTGGCTGGTGACGAGGAGTCCTATGAGGTGTTTGCTGACCTTTTTGACCCCGTCATCAAACTAAGA
CACAACGGCTATGACCCCAGGGTGATGAAGCACACAACGGATCTGGATGCATCAAAGATCACCCAAGGGCAGTTCGA
CGAGCATTACGTGCTGTCTTCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAGCCTGCCTCCAGCCTGCACCC
GGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGGGGGACCTGGCTGGCCGCTAC
TACAAGCTGTCCGAGATGACGGAGCAGGACCAGCAGCGGCTCATCGATGACCACTTTCTGTTTGATAAGCCAGTGTC
CCCTTTATTAACATGTGCTGGGATGGCCCGTGACTGGCCAGATGCCAGGGGAATCTGGCATAATTATGATAAGACAT
TTCTCATCTGGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAGGCAATATGAAACGAGTATTT
GAGCGATTCTGTCGTGGACTAAAAGAAGTAGAACGGTTAATCCAAGAACGAGGCTGGGAGTTCATGTGGAATGAGCG
CCTAGGATACATTTTGACCTGTCCTTCGAACCTTGGAACAGGACTACGAGCTGGTGTCCACGTTAGGATCCCAAAGC
TCAGCAAGGTACTGTTATGTGCCCAGTGGCCCTGATGGGCCAGGATCAGCTCAGATGCGACTGCTTTGTGGAGGAAG
AAAACATCACTGCCCATTCCTTAACCCTTACTTTCTCTATCTACAATATAAAAATAAGAAA
<210> SEQ ID NO 28
<211> Length: 2,632
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 28
>HUMSMCK_T7
TTCCATGCTCTTTAAAAGCCTTATAATTTTCTGGATCTGGGAGCTGGGCTATTTCAGGGTCAATGGATTTATTTCAG
TTGGTGCCTGAACTGACTTGAAACAAGTGTGTGTGGAAAAGAGCTATTTTGAGAAGGAATAAACCGAGACTGCCCTG
ATGATAGAATATGCAAGCTGGTGGGTCTTGACTCCTTAAAGGATTATGAAATTAATTTGATTGGTCCCAATCTTTAT
ATAACCACCCCAATCAGGAAACTTCCCATCCCGCCAAAAGGCCCCCTCACGTGCTCTCCCTGTCAGTACCCCATGCA
AAGGTAAAATAGATGATATTTTTAAACATGGGTCGTGTTTAAAAGAAATGGAAACTCCTTCAGAGAATGAAGGAGAA
CCACACTGGGTAGAAGGTTATTCCTGGGGCTCCACCCCTTGCTCCATCAAGTCCTCTGAGCATGAGCTGGGCTCTGA
GAAGGAAGAGACAGGAACCAATTGGTCATGTCCACGTGGCCTCAGAAGCTGAGTACGTGACGGTCACCAGATGCCTA
GGCAGGCTCCCTTGAAATGGCAGGGCTGCTGTCCAAAATCCTGCTGGGTCATTGCTATTTACAGGCAGCCTTCCCGG
CGTGCGGTGGATATCCCAAGCGGGGCTATTTTTAAGCAGGGCTATGGCCTGCCGTGGGTTAAGCTGGTGTGGACAGA 521
AAGCGAGATGATCTAGCCATCTACTGCAGGGGGCCTGATCTTGAACAGAAACCTGACTGTAATTGTCCCTGGATCCA
GGTCCCAGACAAAGACGCTGGAAGGAGGTCCCTCCAGCCCCTGGCTCAGGGCCCGGTCAGCTGCTGGAGCCAGGCAG CTTGAGACATCCTCCTCTCCGACCTTGGCTTGAGGGGTTCATCCTCCAGAGCTCACCAGGGCCCCAAGGCTGGTACA CCTGAGAGAAGAGAGAAACAAATCCCCCAACAGATGTGCAATTTCACCTGCTGGCCCTTCCATTCTGAGATCCAGAG CCCTGGCAAAGGAGCCTCCAGGACCAGGCCTGGGAAGCAAGACTGGCTCCGCCTTTTACGTTTCAGAGAAAGGGCAG GTGCTATAAAGGGCCCAGCGCCCACGGGCCTGCCTTCAAGGGTACAGCTGTGGGGGCCGGTGCGCCCGGAGGTCTAC GCTGGGATTGGTGAGGTCCTCTGGCCCCGCCCCGCCAGGGAGGATTTCCAGGCCGGCCCGACCAGCTCGCCCTGCAT ACACTTCTTGGCTGTGTGCGCTCAGCAGGACGTGGGAGGCTCCGGCTTCAAGACACTCATCCAAGAGGAAGGATGGC CAGTATCTTTTCTAAGTTGCTAACTGGCCGCAATGCTTCTCTGCTGTTTGCTACCATGGGCACCAGTGTCCTGACCA CCGGGTACCTGCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGGGAGCAGCCTAGGCTATTTCCTCCAAGCGCAGAC TACCCAGACCTGCGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCCCCGCCATTTATGCCAAGCTTCGCAACAA GGTGACACCCAACGGCTACACGCTGGACCAGTGCATCCAGACTGGAGTGGACAACCCTGGCCACCCCTTCATAAAGA CTGTGGGCATGGTGGCTGGTGACGAGGAGTCCTATGAGGTGTTTGCTGACCTTTTTGACCCCGTCATCAAACTAAGA CACAACGGCTATGACCCCAGGGTGATGAAGCACACAACGGATCTGGATGCATCAAAGATCACCCAAGGGCAGTTCGA CGAGCATTACGTGCTGTCTTCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAGCCTGCCTCCAGCCTGCACCC GGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGGGGGACCTGGCTGGCCGCTAC TACAAGCTGTCCGAGATGACGGAGCAGGACCAGCAGCGGCTCATCGATGCATAATTATGATAAGACATTTCTCATCT GGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAGGCAATATGAAACGAGTATTTGAGCGATTC TGTCGTGGACTAAAAGAAGTAGAACGGTTAATCCAAGAACGAGGCTGGGAGTTCATGTGGAATGAGCGCCTAGGATA CATTTTGACCTGTCCTTCGAACCTTGGAACAGGACTACGAGCTGGTGTCCACGTTAGGATCCCAAAGCTCAGCAAGG ACCCACGCTTTTCTAAGATCCTGGAAAACCTAAGACTCCAGAAGCGTGGCACAGGTGGTGTGGACACTGCCGCGGTC GCAGATGTGTACGACATTTCCAACATAGATAGAATTGGTCGATCAGAGGTTGAGCTTGTTCAGATAGTCATCGATGG AGTCAATTACCTGGTGGATTGTGAAAAGAAGTTGGAGAGAGGCCAAGATATTAAGGTGCCACCCCCTCTGCCTCAGT TTGGCAAAAAGTAAACTTTCCCTTTCCCAATTTATAAATAATCTGTCTGCTGGTACGACAGACATAAATCTCTACTC TGAGAGTTTTTATACACTTGGAAAAATATAAAATTGTAGATCCTGCCTATCTTTACAATAAAACTCTCCTTAATATA AAAAACTTTGCTTT
<210> SEQ ID NO 29
<211> Length: 2,382
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 29
>HUMSMCK_T9
TTCCATGCTCTTTAAAAGCCTTATAATTTTCTGGATCTGGGAGCTGGGCTATTTCAGGGTCAATGGATTTATTTCAG
TTGGTGCCTGAACTGACTTGAAACAAGTGTGTGTGGAAAAGAGCTATTTTGAGAAGGAATAAACCGAGACTGCCCTG
ATGATAGAATATGCAAGCTGGTGGGTCTTGACTCCTTAAAGGATTATGAAATTAATTTGATTGGTCCCAATCTTTAT
ATAACCACCCCAATCAGGAAACTTCCCATCCCGCCAAAAGGCCCCCTCACGTGCTCTCCCTGTCAGTACCCCATGCA 522 AAGGTAAAATAGATGATATTTTTAAACATGGGTCGTGTTTAAAAGAAATGGAAACTCCTTCAGAGAATGAAGGAGAA
CCACACTGGGTAGAAGGTTATTCCTGGGGCTCCACCCCTTGCTCCATCAAGTCCTCTGAGCATGAGCTGGGCTCTGA
GAAGGAAGAGACAGGAACCAATTGGTCATGTCCACGTGGCCTCAGAAGCTGAGTACGTGACGGTCACCAGATGCCTA
GGCAGGCTCCCTTGAAATGGCAGGGCTGCTGTCCAAAATCCTGCTGGGTCATTGCTATTTACAGGCAGCCTTCCCGG
CGTGCGGTGGATATCCCAAGCGGGGCTATTTTTAAGCAGGGCTATGGCCTGCCGTGGGTTAAGCTGGTGTGGACAGA
AAGCGAGATGATCTAGCCATCTACTGCAGGGGGCCTGATCTTGAACAGAAACCTGACTGTAATTGTCCCTGGATCCA
GGTCCCAGACAAAGACGCTGGAAGGAGGTCCCTCCAGCCCCTGGCTCAGGGCCCGGTCAGCTGCTGGAGCCAGGCAG
CTTGAGACATCCTCCTCTCCGACCTTGGCTTGAGGGGTTCATCCTCCAGAGCTCACCAGGGCCCCAAGGCTGGTACA
CCTGAGAGAAGAGAGAAACAAATCCCCCAACAGATGTGCAATTTCACCTGCTGGCCCTTCCATTCTGAGATCCAGAG
CCCTGGCAAAGGAGCCTCCAGGACCAGGCCTGGGAAGCAAGACTGGCTCCGCCTTTTACGTTTCAGAGAAAGGGCAG
GTGCTATAAAGGGCCCAGCGCCCACGGGCCTGCCTTCAAGGGTACAGCTGTGGGGGCCGGTGCGCCCGGAGGTCTAC
GCTGGGATTGGTGAGGTCCTCTGGCCCCGCCCCGCCAGGGAGGATTTCCAGGCCGGCCCGACCAGCTCGCCCTGCAT
ACACTTCTTGGCTGTGTGCGCTCAGCAGGACGTGGGAGGCTCCGGCTTCAAGACACTCATCCAAGAGGAAGGATGGC
CAGTATCTTTTCTAAGTTGCTAACTGGCCGCAATGCTTCTCTGCTGTTTGCTACCATGGGCACCAGTGTCCTGACCA
CCGGGTACCTGCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGGGAGCAGCCTAGGCTATTTCCTCCAAGCGCAGAC
TACCCAGACCTGCGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCCCCGCCATTTATGCCAAGCTTCGCAACAA
GGTGACACCCAACGGCTACACGCTGGACCAGTGCATCCAGACTGGAGTGGACAACCCTGGCCACCCCTTCATAAAGA
CTGTGGGCATGGTGGCTGGTGACGAGGAGTCCTATGAGGTGTTTGCTGACCTTTTTGACCCCGTCATCAAACTAAGA
CACAACGGCTATGACCCCAGGGTGATGAAGCACACAACGGATCTGGATGCATCAAAGATCACCCAAGGGCAGTTCGA
CGAGCATTACGTGCTGTCTTCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAGCCTGCCTCCAGCCTGCACCC
GGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGGGGGACCTGGCTGGCCGCTAC
TACAAGCTGTCCGAGATGACGGAGCAGGACCAGCAGCGGCTCATCGATGACCACTTTCTGTTTGATAAGCCAGTGTC
CCCTTTATTAACATGTGCTGGGATGGCCCGTGACTGGCCAGATGCCAGGGGAATCTGGCATAATTATGATAAGACAT
TTCTCATCTGGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAGGCAATATGAAACGAGTATTT
GAGCGATTCTGTCGTGGACTAAAAGAAGTAAGATGTTATCTGAGATTTCTGGATATTTATTAAAATAAAATTACCGT
ATTGTTTGTTCTTGAAAGAAGACACTATGGTAACTTCCAAGATGGAGCTAATTTTTTTCTAGAAATCAAAGCAACTG
CCGCCTCCCAGGTTCAAGTGATTATCCCGCCTCAGCCTCTAGAGTAGCTGGGATTACAGGTGCCACCACCAC
<210> SEQ ID NO 30
<211> Length: 2,296
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 30
>HUMSMCK_T11
TTCCATGCTCTTTAAAAGCCTTATAATTTTCTGGATCTGGGAGCTGGGCTATTTCAGGGTCAATGGATTTATTTCAG
TTGGTGCCTGAACTGACTTGAAACAAGTGTGTGTGGAAAAGAGCTATTTTGAGAAGGAATAAACCGAGACTGCCCTG 523
ATGATAGAATATGCAAGCTGGTGGGTCTTGACTCCTTAAAGGATTATGAAATTAATTTGATTGGTCCCAATCTTTAT
ATAACCACCCCAATCAGGAAACTTCCCATCCCGCCAAAAGGCCCCCTCACGTGCTCTCCCTGTCAGTACCCCATGCA AAGGTAAAATAGATGATATTTTTAAACATGGGTCGTGTTTAAAAGAAATGGAAACTCCTTCAGAGAATGAAGGAGAA CCACACTGGGTAGAAGGTTATTCCTGGGGCTCCACCCCTTGCTCCATCAAGTCCTCTGAGCATGAGCTGGGCTCTGA GAAGGAAGAGACAGGAACCAATTGGTCATGTCCACGTGGCCTCAGAAGCTGAGTACGTGACGGTCACCAGATGCCTA GGCAGGCTCCCTTGAAATGGCAGGGCTGCTGTCCAAAATCCTGCTGGGTCATTGCTATTTACAGGCAGCCTTCCCGG CGTGCGGTGGATATCCCAAGCGGGGCTATTTTTAAGCAGGGCTATGGCCTGCCGTGGGTTAAGCTGGTGTGGACAGA AAGCGAGATGATCTAGCCATCTACTGCAGGGGGCCTGATCTTGAACAGAAACCTGACTGTAATTGTCCCTGGATCCA GGTCCCAGACAAAGACGCTGGAAGGAGGTCCCTCCAGCCCCTGGCTCAGGGCCCGGTCAGCTGCTGGAGCCAGGCAG CTTGAGACATCCTCCTCTCCGACCTTGGCTTGAGGGGTTCATCCTCCAGAGCTCACCAGGGCCCCAAGGCTGGTACA CCTGAGAGAAGAGAGAAACAAATCCCCCAACAGATGTGCAATTTCACCTGCTGGCCCTTCCATTCTGAGATCCAGAG CCCTGGCAAAGGAGCCTCCAGGACCAGGCCTGGGAAGCAAGACTGGCTCCGCCTTTTACGTTTCAGAGAAAGGGCAG GTGCTATAAAGGGCCCAGCGCCCACGGGCCTGCCTTCAAGGGTACAGCTGTGGGGGCCGGTGCGCCCGGAGGTCTAC GCTGGGATTGGTGAGGTCCTCTGGCCCCGCCCCGCCAGGGAGGATTTCCAGGCCGGCCCGACCAGCTCGCCCTGCAT ACACTTCTTGGCTGTGTGCGCTCAGCAGGACGTGGGAGGCTCCGGCTTCAAGACACTCATCCAAGAGGAAGGATGGC CAGTATCTTTTCTAAGTTGCTAACTGGCCGCAATGCTTCTCTGCTGTTTGCTACCATGGGCACCAGTGTCCTGACCA CCGGGTACCTGCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGGGAGCAGCCTAGGCTATTTCCTCCAAGCGCAGAC TACCCAGACCTGCGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCCCCGCCATTTATGCCAAGCTTCGCAACAA GGTGACACCCAACGGCTACACGCTGGACCAGTGCATCCAGACTGGAGTGGACAACCCTGGCCACCCCTTCATAAAGA CTGTGGGCATGGTGGCTGGTGACGAGGAGTCCTATGAGGTGTTTGCTGACCTTTTTGACCCCGTCATCAAACTAAGA CACAACGGCTATGACCCCAGGGTGATGAAGCACACAACGGATCTGGATGCATCAAAGATCACCCAAGGGCAGTTCGA CGAGCATTACGTGCTGTCTTCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAGCCTGCCTCCAGCCTGCACCC GGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGGGGGACCTGGCTGGCCGCTAC TACAAGCTGTCCGAGATGACGGAGCAGGACCAGCAGCGGCTCATCGATGCATAATTATGATAAGACATTTCTCATCT GGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAGGCAATATGAAACGAGTATTTGAGCGATTC TGTCGTGGACTAAAAGAAGTAAGATGTTATCTGAGATTTCTGGATATTTATTAAAATAAAATTACCGTATTGTTTGT TCTTGAAAGAAGACACTATGGTAACTTCCAAGATGGAGCTAATTTTTTTCTAGAAATCAAAGCAACTGCCGCCTCCC AGGTTCAAGTGATTATCCCGCCTCAGCCTCTAGAGTAGCTGGGATTACAGGTGCCACCACCAC
<210> SEQ ID NO 31
<211> Length: 3,189
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 31 >H88 95_PEA_3_T3
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC 524 TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG
TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA
GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCATCATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC
AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA
AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGGTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCC
TGTGTGGCTACTGCTCCTTCTGCAATCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAG
CACTGCGACCAGTGCCAGGTGAGACCTCACCTCACACTCAAGGCTCCACTGGGCCTCAGGATGCACCGGGACCCTCT
GAGGACCCCCAGCCCTAAATCCTGGCCTCTGACCCAACCCCTTACCCCTGATGCAACCTTGACTCCACAAGCGATCC
TGACTCCAACCTTAACCTAGACCTAGCCTCTGGTCCGGGTCTGGTCCCGGCCCCATCCTAACTCCGCCCCCGGCCAC
GCCCCACGCTCACTCTCTCTCCCCGTCCCCGCCTCCAGCACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAA
ACGGTCTGCGCTCCAGGAAGCTACGTTGACTATTTCTCCTCGTCCCTTTATCAGGCCCTGGCAGACATGCTGGAAAC 525 GCCGGAACCCTGACCCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGCCTTCCAACCCCTTTCCACGAGCTA
TATTTATTTCTCCGAATAAACGTGCTCCCCGA
<210> SEQ ID NO 32
<211> Length: 3,298
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 32
>H88495_PEA_3_T4
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG
ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG
TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA
GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCATCATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC
AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA 526 AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGGTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCC
TGTGTGGCTACTGCTCCTTCTGCAATCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAG
CACTGCGACCAGTGCCAGGTGAGACCTCACCTCACACTCAAGGCTCCACTGGGCCTCAGGATGCACCGGGACCCTCT
GAGGACCCCCAGCCCTAAATCCTGGCCTCTGACCCAACCCCTTACCCCTGATGCAACCTTGACTCCACAAGCGATCC
TGACTCCAACCTTAACCTAGACCTAGCCTCTGGTCCGGGTCTGGTCCCGGCCCCATCCTAACTCCGCCCCCGGCCAC
GCCCCACGCTCACTCTCTCTCCCCGTCCCCGCCTCCAGCACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAA
ACGGTCTGCGCTCCAGGAAGCTACGTTGACTATTTCTCCTCGTCCCTTTATCAGGCCCTGGCAGACATGCTGGAAAC
GCCGGAACCCTGACCCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGCCTTCCAACCCCTTTCCACGAGCTA
TATTTATTTCTCCGAATAAACGTGCTCCCCGAAACCTCATTGTCAGACGTGGGGTCTGGGAATCTCAGGGCATCGGG
GAATGCGGGTAGGGTCTAGAGACCTGGACCTAGACTTGAGGGATGAGGGGCCTGGACTCCTGGC
<210> SEQ ID NO 33
<211> Length: 3,257
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 33
>H88495_PEA_3_T5
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG
ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG
TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA 527 GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCATCATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC
AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA
AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGGTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCC
TGTGTGGCTACTGCTCCTTCTGCAATCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAG
CACTGCGACCAGTGCCAGCACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAAACGGTCTGCGCTCCAGGTGA
GCATGGGCGGGGCCCTGGAAAAACCTGAGGAAGGTGCCGGGCCCAGCGTGGTGAATCCTGGTGGGGGCGGAGCCTGG
CCCGGTAGGCTGGTGGGGCGGGGCTAAGAGGGGAGGCGTGGCCAAGGCTCTGAGCACGTGGGCCGGGGCCTGGCTCG
AGGAACACCAGGTGGAGTTGCTGGAGCCAAGGGACAGAAATGAGTGGAGGGTTGAGATGCGGGCTTAGAGCCTAATG
GGCGAGGCCAACTCAAGTAGGAATCGAAGGGGCGGGGCTACTGGAGAACGGAATCACCCAGAACGAAAAAGGGGTCC
GGTAGAAGGGATTCAGTTGACTATTTCTCCTCGTCCCTTTATCAGGCCCTGGCAGACATGCTGGAAACGCCGGAACC
CTGACCCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGCCTTCCAACCCCTTTCCACGAGCTATATTTATTT
CTCCGAATAAACGTGCTCCCCGA
<210> SEQ ID NO 34
<211> Length: 3,366
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 34
>H88 95_PEA_3_T6
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG 528 ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG
TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA
GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCATCATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC
AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA
AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGGTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCC
TGTGTGGCTACTGCTCCTTCTGCAATCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAG
CACTGCGACCAGTGCCAGCACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAAACGGTCTGCGCTCCAGGTGA
GCATGGGCGGGGCCCTGGAAAAACCTGAGGAAGGTGCCGGGCCCAGCGTGGTGAATCCTGGTGGGGGCGGAGCCTGG
CCCGGTAGGCTGGTGGGGCGGGGCTAAGAGGGGAGGCGTGGCCAAGGCTCTGAGCACGTGGGCCGGGGCCTGGCTCG
AGGAACACCAGGTGGAGTTGCTGGAGCCAAGGGACAGAAATGAGTGGAGGGTTGAGATGCGGGCTTAGAGCCTAATG 529 GGCGAGGCCAACTCAAGTAGGAATCGAAGGGGCGGGGCTACTGGAGAACGGAATCACCCAGAACGAAAAAGGGGTCC
GGTAGAAGGGATTCAGTTGACTATTTCTCCTCGTCCCTTTATCAGGCCCTGGCAGACATGCTGGAAACGCCGGAACC
CTGACCCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGCCTTCCAACCCCTTTCCACGAGCTATATTTATTT
CTCCGAATAAACGTGCTCCCCGAAACCTCATTGTCAGACGTGGGGTCTGGGAATCTCAGGGCATCGGGGAATGCGGG
TAGGGTCTAGAGACCTGGACCTAGACTTGAGGGATGAGGGGCCTGGACTCCTGGC
<210> SEQ ID NO 35
<211> Length: 3,508
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 35
>H88495_PEA_3_T7
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG
ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG
TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA
GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCATCATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC 530 AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA
AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGGTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCC
TGTGTGGCTACTGCTCCTTCTGCAATCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAG
CACTGCGACCAGTGCCAGGTGAGACCTCACCTCACACTCAAGGCTCCACTGGGCCTCAGGATGCACCGGGACCCTCT
GAGGACCCCCAGCCCTAAATCCTGGCCTCTGACCCAACCCCTTACCCCTGATGCAACCTTGACTCCACAAGCGATCC
TGACTCCAACCTTAACCTAGACCTAGCCTCTGGTCCGGGTCTGGTCCCGGCCCCATCCTAACTCCGCCCCCGGCCAC
GCCCCACGCTCACTCTCTCTCCCCGTCCCCGCCTCCAGCACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAA
ACGGTCTGCGCTCCAGGTGAGCATGGGCGGGGCCCTGGAAAAACCTGAGGAAGGTGCCGGGCCCAGCGTGGTGAATC
CTGGTGGGGGCGGAGCCTGGCCCGGTAGGCTGGTGGGGCGGGGCTAAGAGGGGAGGCGTGGCCAAGGCTCTGAGCAC
GTGGGCCGGGGCCTGGCTCGAGGAACACCAGGTGGAGTTGCTGGAGCCAAGGGACAGAAATGAGTGGAGGGTTGAGA
TGCGGGCTTAGAGCCTAATGGGCGAGGCCAACTCAAGTAGGAATCGAAGGGGCGGGGCTACTGGAGAACGGAATCAC
CCAGAACGAAAAAGGGGTCCGGTAGAAGGGATTCAGTTGACTATTTCTCCTCGTCCCTTTATCAGGCCCTGGCAGAC
ATGCTGGAAACGCCGGAACCCTGACCCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGCCTTCCAACCCCTT
TCCACGAGCTATATTTATTTCTCCGAATAAACGTGCTCCCCGA
<210> SEQ ID NO 36
<211> Length: 2,955
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 36
>H88495_PEA_3_T8
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG
ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG 531 TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA
GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATC :ATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC
AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA
AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGGTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCC
TGTGTGGCTACTGCTCCTTCTGCAATCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAG
CACTGCGACCAGTGCCAGGGCCCTGGCAGACATGCTGGAAACGCCGGAACCCTGACCCAGTCGCTCGACTGCGACGC
AGGTGTACCTCCCCCTGCCTTCCAACCCCTTTCCACGAGCTATATTTATTTCTCCGAATAAACGTGCTCCCCGAAAC
CTCATTGTCAGACGTGGGGTCTGGGAATCTCAGGGCATCGGGGAATGCGGGTAGGGTCTAGAGACCTGGACCTAGAC
TTGAGGGATGAGGGGCCTGGACTCCTGGC
<210> SEQ ID NO 37
<211> Length: 2,867
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 37 >H88495 PEA 3 T9 532 GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG
ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT
TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAACCCCAAAGGGACAAAGACCCCAACGTTTG
TCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCCATGGGCCACCATAGGCCATGGCTGCACG
CTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCATGACCCAGCAGCTCAGAGGGGATGGGCTG
GGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGGAGGCATCAGCAGAGCTTCGCCACCACCT
CCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAGAATGGGCATCATTTCTGGAGCCACCCAG
ACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACTCCCAGGCCACAGGTCCCAAGACCACAAA
GTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTGGGCAGGCCCGTGGGCACAGAGGCCACGG
GAGTGAAGACACGGAAGACTCAGCTGAGCACAGGCACCACCTCCCCAGCCACAGGAGCCACAGCCATCAAGACGAGG
ATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGACACCGAGGCCATGATGGGGAAGAT
GATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACTGAGTATGGACACCAGGCCCACAG
GCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCATCATGGCCCCAGCCACAGGCACC
AAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATGATGATGATGTCTCCATTGAATAT
AGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTCTCAGATGGACACCATCATCGCGA
CCCCAGCCACAGGCACCGAAGCCATGAAGAAGATGACAATGATGATGATGATGTCTCCACTGAGTATGGACACCAGG
CCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCACCATCATGTCCCTGACCAC
AGGCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCACTGAACGTTGGCACCAGGGTCCCCAACATGT
CCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAGTCCAGTTCGGCCACTATGTTGCAAGCCACC
AACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTATAAAACAGAAGTCCCTCACCATCACCACCAC
AGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCACCAGGCCCCCAGCCACAGGCAAAGCCACCA
AGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGAGCCATCACCCCCCAGGACACACAGTGGTCA
AGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAGAAGGAAGAGGACCCCGGCTCCCATGAGGAA
GACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAGCCGGGACCAGGAAGATGAGGAGGATGAGGA
GGAAGGTCATGGCCTCAGCCTGAACCAGGAGGAGGAAGAAGAGGAAGACAAGGAGGAGGAGGAGGAGGAAGAAGACG
AGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGAGGAGGAGGAG
GAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAACCCACTGGACAGGAGAGAGGAGGCTGGAGGTGC
CTCCAGCGAGGAGGAAAGCGGTGAGGACACAGCGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATG
GGTGAGCACTGCGACCAGTGCCAGCACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAAACGGTCTGCGCTCC
AGGAAGCTACGTTGACTATTTCTCCTCGTCCCTTTATCAGGCCCTGGCAGACATGCTGGAAACGCCGGAACCCTGAC
CCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGCCTTCCAACCCCTTTCCACGAGCTATATTTATTTCTCCG
AATAAACGTGCTCCCCGA 533
<210> SEQ ID NO 38
<211> Length: 2,064
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 38
>Z36249_PEA_3_T2
ACATATTCAGCAGGGTTAGCTTGTCCTCCCCTCCCTCTTCAGCTTCCCAGACACTGAGTCTGGAATGAAAATTCACC
TGCCTCTGAGTTGGCTCCTAATGGGGGTGGGAGTGTTACTTCGGTTCCCAGGTTGGAAGATTATCTCACCCGGCCCC
AGCTATATAAGCTGACCGGTGTGGAGGGGCCCAGCAGGGCCAACTCCAGGGATTCCTTCCACGACAGAAAAACATAC
AAGACTCCTTCAGCCAACATGATGGTACTGAAAGTAGAGGAACTGGTCACTGGAAAGAAGAATGGCAATGGGGAGGC
AGGGGAATTCCTTCCTGAGGATTTCAGAGATGGAGAGTATGAAGCTGCTGTTACTTTAGAGAAGCAGGAGGATCTGA
AGACACTTCTAGCCCACCCTGTGACCCTGGGGGAGCAACAGTGGAAAAGCGAGAAACAACGAGAGGCAGAGCTCAAA
AAGAAAAAACTAGAACAAAGATCAAAGCTTGAAAATTTAGAAGACCTTGAAATAATCATTCAACTGAAGAAAAGGAA
AAAATACAGGAAAACTAAAGTTCCAGTTGTAAAGGAACCAGAACCTGAAATCATTTATAAACGGACAGCTCTTCATA
GAGCATGCTTGGAAGGACATTTGGCAATTGTGGAGAAGTTAATGGAAGCTGGAGCCCAGATCGAATTCCGTGATATG
CTTGAATCCACAGCCATCCACTGGGCAAGCCGTGGAGGAAACCTGGATGTTTTAAAATTGTTGCTGAATAAAGGAGC
AAAAATTAGCGCCCGAGATAAGTTGCTCAGCACAGCGCTGCATGTGGCGGTGAGGACTGGCCACTATGAGTGCGCGG
AGCATCTTATCGCCTGTGAGGCAGACCTCAACGCCAAAGACAGAGAAGGAGATACCCCGTTGCATGATGCGGTGAGA
CTGAACCGCTATAAGATGATCCGACTCCTGATTATGTATGGCGCGGATCTCAACATCAAGAACTGTGCTGGGAAGAC
GCCGATGGATCTGGTGCTACACTGGCAGAATGGAACCAAAGCAATATTCGACAGCCTCAGAGAGAACTCCTACAAGA
CCTCTCGCATAGCTACATTCTGAGGCAAACGACAGACTCTTAATCAGTAAATGTTCACTGGCATTTTGAAGGCATGG
CCCAAGAGAAGAGACACTAGCCATAAAATCTAGTTTCTATTTATCAACGTGTTGTGAAGATGTACCTAATGAAGTTT
TGAGAAAGCACAGGGTTATAGGTGTTTAAATTTCCTTTAGTGAAACTCTTATTTATTTTTATGTATTCCTGTTTATT
TATTTACTGCCACGCTACTGATATTCAGACCTTCATGATCATCCATCTGGTGAGCAGAGCTTCATTTGTATATAACA
CTTTCAGAGCCTTCCCACCCATAGGTAGTTCTTAAACCAGGTGAAAGAGCAAAGTTCAAGTGCCTACTTATGTGTCA
TTCGCTCATGTAAGAGTTTTTAAGAGAGGGCTGATTATCACAGCCCTCTTTTCTCCTGAATTTTTAATGCAGAAGTT
TGAATGAAGCAAGGGAAGGCATGTAGGGACAGGAAAGGAAACAATGGAAGGAAAGTGATTCTGTGAAAAGGACAGTG
AAGCCAGCTATTTTACCCCCAGGCTGGATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACCGAGTACACAGAGTACC
CAAGTGAAGAGAACGTCATGAGTGTAAGTGCAAATCAGTGGAAGGAGCGGCAAACTGGGACATGCAGAATTGAATTT
GCTCAAAAAAGATGAAAGGAAATGCAAACTGTAAATGTATAAATGTATATTGTATTGTATGTACATTTTATATTCAT
AATAAAGGCAATCAAACTCTAAACCTCTAAGTCCTTCTATAAGTGTGGTGGAAATGTCCTATGTGAAAAAAAAAGCT
ATATAGGAGGGTTTTTTTTTTCCATTGTTTTCCAAGTTTTGCAGATTAGAAATGTCCCGTACAACAGCACTCCCAGT
ATTTAATATGTATACAGATCACCTGGGGATCTGGTTAAAATGCAGATTTCTGATTCAGCTGG
<210> SEQ ID NO 39 <211> Length: 1,472 534 <212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 39
>Z36249_PEA_3_T3
ACATATTCAGCAGGGTTAGCTTGTCCTCCCCTCCCTCTTCAGCTTCCCAGACACTGAGTCTGGAATGAAAATTCACC
TGCCTCTGAGTTGGCTCCTAATGGGGGTGGGAGTGTTACTTCGGTTCCCAGGTTGGAAGATTATCTCACCCGGCCCC
AGCTATATAAGCTGACCGGTGTGGAGGGGCCCAGCAGGGCCAACTCCAGGGATTCCTTCCACGACAGAAAAACATAC
AAGACTCCTTCAGCCAACATGATGGTACTGAAAGTAGAGGAACTGGTCACTGGAAAGAAGAATGGCAATGGGGAGGC
AGGGGAATTCCTTCCTGAGGATTTCAGAGATGGAGAGTATGAAGCTGCTGTTACTTTAGAGAAGCAGGAGGATCTGA
AGACACTTCTAGCCCACCCTGTGACCCTGGGGGAGCAACAGTGGAAAAGCGAGAAACAACGAGAGGCAGAGCTCAAA
AAGAAAAAACTAGAACAAAGATCAAAGCTTGAAAATTTAGAAGACCTTGAAATAATCATTCAACTGAAGAAAAGGAA
AAAATACAGGAAAACTAAAGTTCCAGTTGTAAAGGAACCAGAACCTGAAATCATTACGGAACCTGTGGATGTGCCTA
CGTTTCTGAAGGCTGCTCTGGAGAATAAACTGCCAGTAGTAGAAAAATTCTTGTCAGACAAGAACAATCCAGATGTT
TGTGATGAGTATAAACGGACAGCTCTTCATAGAGCATGCTTGGAAGGACATTTGGCAATTGTGGAGAAGTTAATGGA
AGCTGGAGCCCAGATCGAATTCCGTGATATGGTAAATATATTTCTTTGCTTGGGAATGAGCCAAAAGAAGTAGACTA
TATGAAGCTCCGGAAAACCTCCAATGCAAAACCGAGCTGATTGGATTGAAAATTGATCTGAGAGAACTAGGCAAAAG
CTCATTTCTCCAAATAAAGGAAAGTTGGGAGATGAGAGTAGGTCATGTGAAAATATTTTCCATACATACTGAAAATA
GAGGAATATTTCAGGGAAAAGAAGGAAGTGAAAGCTGTTAAACTGAATTCAATATCCTCATCAGCGAGTTAGTCATT
CATTTTCGACACTTGCCTTTCAACAGCCTTGTCCCTCCATTGTTCACAGGGCAGCCTGCTTATGGTTGGCTGCCAGC
AACATATACGAATTCTCTAGCTGCACACTTTATATGATAGATGCCAATTGCTACCAATGAGATTTGGGGCTAGACTG
CATATGAAATGAATTGCATCTATGGAAAGTAGCTGCTATTCAGACCTCAATAATTCAATCACTGTGATTTCTACGAA
GACCAGTATGCAGCATAATTTATGAACTGAAGATTGAGCTGGGAAAATTCTTTATGTATTTAAATGCAGCTCATTTT
GACTTTATAGCAAAGCGGCAACGGGATATCAAAGAAATCCAAGGGACTTGGCCAAAATTGAATCCAAAACATAAACA
CATTGAAAA
<210> SEQ ID NO 40
<211> Length: 1,387
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 40
>Z36249_PEA_3_T5
ACATATTCAGCAGGGTTAGCTTGTCCTCCCCTCCCTCTTCAGCTTCCCAGACACTGAGTCTGGAATGAAAATTCACC
TGCCTCTGAGTTGGCTCCTAATGGGGGTGGGAGTGTTACTTCGGTTCCCAGGTTGGAAGATTATCTCACCCGGCCCC
AGCTATATAAGCTGACCGGTGTGGAGGGGCCCAGCAGGGCCAACTCCAGGGATTCCTTCCACGACAGAAAAACATAC
AAGACTCCTTCAGCCAACATGATGGTACTGAAAGTAGAGGAACTGGTCACTGGAAAGAAGAATGGCAATGGGGAGGC
AGGGGAATTCCTTCCTGAGGATTTCAGAGATGGAGAGTATGAAGCTGCTGTTACTTTAGAGAAGCAGGAGGATCTGA 535 AGACACTTCTAGCCCACCCTGTGACCCTGGGGGAGCAACAGTGGAAAAGCGAGAAACAACGAGAGGCAGAGCTCAAA
AAGAAAAAACTAGAACAAAGATCAAAGCTTGAAAATTTAGAAGACCTTGAAATAATCATTCAACTGAAGAAAAGGAA
AAAATACAGGAAAACTAAAGTTCCAGTTGTAAAGGAACCAGAACCTGAAATCATTACGGAACCTGTGGATGTGCCTA
CGTTTCTGAAGGCTGCTCTGGAGAATAAACTGCCAGTAGTAGAAAAATTCTTGTCAGACAAGAACAATCCAGATGTT
TGTGATGAGGTAAGACTCATGCAAAGCACTGCAAAATCCAGCTCATTAATTTTATGTTTCTTATGCTTTACTCCAGT
CTTGCTAATATAGTGCCAAAGTCCTTCCACCTGAAACAGTTTCCCCAGCTGTTGCTGTGTATGCCAGGAGCCTAATA
GGAGAGTTCAGTGGTCCAAAAAATAAATAGATATTAGATCAGTGATACGGATTGCATTGTTTTTTGCACTCATATAC
ATCTGGCTGATTTTTCAGTTTTTCTTTAACTTCTTAGATTCTTGGGATAAGACTTTTAATGTGGGCCAAAAAGTCAC
CTTTAGAGATATATTATTAGCATCATCTTTGATTAAAACCAAGCACGTCAACACTAGATAAGAAATCTGGAGATTGG
AGTTCAGGGGCCAGTTGTACCACTACTTGGCTATTTGGTTTTGAGCAGCTAATTTGCATCCTCTGGGCTGTGGTTTC
CTTATCTGTAAACATGGGGCATTGGAGTGAAATAACGCCTAAAGTTGTTCCAGCTCTAATAGTTCATTAGCCCATTC
AAATAAAGCCAATTTATCAGAAATCACTAATCTTTTTGTATTCTTTCCCCCATGAAGTGAAATTGGGGACCGCTTCT
GAAGTTGAACTAAAAACATGTCTCCCATTCTCCTAAAAATGAATGGAAACTTTTTGATAGTCTAGCAACAGTCCCAG
A
<210> SEQ ID NO 41
<211> Length: 1,877
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 41
>Z36249_PEA_3_T9
ACATATTCAGCAGGGTTAGCTTGTCCTCCCCTCCCTCTTCAGCTTCCCAGACACTGAGTCTGGAATGAAAATTCACC
TGCCTCTGAGTTGGCTCCTAATGGGGGTGGGAGTGTTACTTCGGTTCCCAGGTTGGAAGATTATCTCACCCGGCCCC
AGCTATATAAGCTGACCGGTGTGGAGGGGCCCAGCAGGGCCAACTCCAGGGATTCCTTCCACGACAGAAAAACATAC
AAGACTCCTTCAGCCAACATGATGGTACTGAAAGTAGAGGAACTGGTCACTGGAAAGAAGAATGGCAATGGGGAGGC
AGGGGAATTCCTTCCTGAGGATTTCAGAGATGGAGAGTATGAAGCTGCTGTTACTTTAGAGAAGCAGGAGGATCTGA
AGACACTTCTAGCCCACCCTGTGACCCTGGGGGAGCAACAGTGGAAAAGCGAGAAACAACGAGAGGCAGAGCTCAAA
AAGAAAAAACTAGAACAAAGATCAAAGCTTGAAAATTTAGAAGACCTTGAAATAATCATTCAACTGAAGAAAAGGAA
AAAATACAGGAAAACTAAAGTTCCAGTTGTAAAGGAACCAGAACCTGAAATCATTACGGAACCTGTGGATGTGCCTA
CGTTTCTGAAGGCTGCTCTGGAGAATAAACTGCCAGTAGTAGAAAAATTCTTGTCAGACAAGAACAATCCAGATGTT
TGTGATGAGCTTGAATCCACAGCCATCCACTGGGCAAGCCGTGGAGGAAACCTGGATGTTTTAAAATTGTTGCTGAA
TAAAGGAGCAAAAATTAGCGCCCGAGATAAGTTGCTCAGCACAGCGCTGCATGTGGCGGTGAGGACTGGCCACTATG
AGTGCGCGGAGCATCTTATCGCCTGTGAGGCAGACCTCAACGCCAAAGACAGAGAAGGAGATACCCCGTTGCATGAT
GCGGTGAGACTGAACCGCTATAAGATGATCCGACTCCTGATTATGTATGGCGCGGATCTCAACATCAAGAACTGTGC
TGGGAAGACGCCGATGGATCTGGTGCTACACTGGCAGAATGGAACCAAAGCAATATTCGACAGCCTCAGAGAGAACT
CCTACAAGACCTCTCGCATAGCTACATTCTGAGGCAAACGACAGACTCTTAATCAGTAAATGTTCACTGGCATTTTG
AAGGCATGGCCCAAGAGAAGAGACACTAGCCATAAAATCTAGTTTCTATTTATCAACGTGTTGTGAAGATGTACCTA 536
ATGAAGTTTTGAGAAAGCACAGGGTTATAGGTGTTTAAATTTCCTTTAGTGAAACTCTTATTTATTTTTATGTATTC
CTGTTTATTTATTTACTGCCACGCTACTGATATTCAGACCTTCATGATCATCCATCTGGTGAGCAGAGCTTCATTTG TATATAACACTTTCAGAGCCTTCCCACCCATAGGTAGTTCTTAAACCAGGTGAAAGAGCAAAGTTCAAGTGCCTACT TATGTGTCATTCGCTCATGTAAGAGTTTTTAAGAGAGGGCTGATTATCACAGCCCTCTTTTCTCCTGAATTTTTAAT GCAGAAGTTTGAATGAAGCAAGGGAAGGCATGTAGGGACAGGAAAGGAAACAATGGAAGGAAAGTGATTCTGTGAAA AGGACAGTGAAGCCAGCTATTTTACCCCCAGGCTGGATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACCGAGTACA CAGAGTACCCAAGTGAAGAGAACGTCATGAGTGTAAGTGCAAATCAGTGGAAGGAGCGGCAAACTGGGACATGCAGA ATTGAATTTGCTCAAAAAAGATGAAAGGAAATGCAAACTGTAAATGTATAAATGTATATTGTATTGTATGTACATTT TATATTCATAATAAAGGCAATCAAACTCT
<210> SEQ ID NO 42
<211> Length: 868
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 42
>Z25377_PEA_1_T1
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG
GTGGGGACTGGGCACATCATCAATACGATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTT
TAATGGGATTGTGGAAGAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCA
CACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTATTTAC
CGTGGTTTCTGGGCAGTCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGTGCAGC
CCCCTTCGCCAGCCATTTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAGATGGAATTTCTTCTCTCTGTT
ACTCAAGCCTCTCAAAGTCCTTATTGTCCCAGCCTCTGCGTGAAACGTCTTCAGCCATCAATGACATCTCACTCCTT
CAAGCCCTTATGCCACTGCTGGGATGGACCAGTCACTGGACCTGCATTACAGTGGGCTTATATTGACCTTTACCTCT
ACACTTGTATATAACTCGTTTTCCCATTTAGTTGCAAGACACTTGGAAGCACAGACCAAGGCTTACATTTGTGTTTT
AATGTTTTTCTTGTAAATGCTTTATGCCTAAATGTTTCTGTACTACTCTTCTTTCCAAATCCTTATTGTTTAAAAGT
TTCTCTCCTACTATACCATGCCTTATAAATATTGATTGAATGAATGGATGAAATGCATACCTGCTTATATTTCTAAT
TAAAGGCAATTTGGGATTATA
<210> SEQ ID NO 43
<211> Length: 3,969
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 43
>Z25377_PEA_1_T5
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG 537 GTGGGGACTGGGCACATCATCAATACGATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTT
TAATGGGATTGTGGAAGAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCA
CACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTAGCATC
CTATTTTCATTGGTGGTGATGCTGTATGTCATCTGGGTCCAGGCAGTGGCTGACATGGAAAGCTACCGAAACATGAA
AATGAAGGACTGCCTGGATTTCACCCCTTCTGTTCTGTATGGCTGGTCATTTTTCCTGGCCCCAGCTGGGATATTTT
TTTCTTTGCTAGCTGGATTACTATTTCTGGTTGTTGGACGGCATATTCAGATACATCACTAAATCAACTGTTGCCAC
AAGTATTTTCTTGAGAGATTTTAAAACAAGGAATACTTTTTTTCCATTTTGTTTCATTGATCCCAGCATAAAGTTAG
TAGATATAACTTTTTAGTTGCTATTCAAATTAATCATTTTACTAAAATTTTCTTCAGTAAGAAGGTCCTAGAATCTC
TCCAGACACCAGCAAGCCTCTATCTTGTCTAAGTGCTGTCAAGGACCTAGTTCTTTAGGGAATAGGTAAACAGGTCT
CCCTTTCATTGAACATGTTAGAGTTCATGCAGGTCGCAAAGGCCTGATAATAGCTTAATACCATGACATGGGGAAAA
TCTCGATAGATTTGGCTTAAAGTCTCCTTGGCATTCACTTCTGCTAATTAAAAAAAATCCTTGAAGAATAATTAAGA
ATGGGCAAGGTTGTCAGAGAATTTATTTTGTTTCTTGCCCACACAGATAATATCCACATACACATTCACTGGCTCTT
GTGAGCAAATGAATTTAAAAATAGACAGCAGTTGTTCTAATTAGTGGGAGCCATGTACTCACCAGTTAAAATGGGCC
ACAACAAACAAGACTGAGAGCATGTACTTATCTTGCTTTTTCACCAACAGTGGTTTGGTTACCTAGTTTTATTCACT
TAATTGTGCATGCTTACATAAACTTTAAACTACATTTAAAACTAGCAAATCTGCATACCAAATTATGTATAACGTAG
ATTGAATTTTTATGAACTTAAAGTGAGTTAATTGTATAATGTAATATTGTTTAAAATATGTAAAAACCAAGCATTTC
CGCTTGGTCCATAATTCTATTTGATATTTTAAAATTCTCATTTAAAAATTATATTGCTATCATTCAGCATGTGAAAA
TTTATTGATAAAATGTGATTTTAATATTTTTTAGATATAAACTTTCAACGTACTTCCATATGAGGATTATAATAGCC
CTGCTTTATTAAAGACCATAAAATATTAACTTTCCCCAAGATGTTATGGGTTCCAGTTCTTCTGATCATTTGATTCC
TTTAATTACTGTCCCTCAATTTCTTCATCTTTACAATAGATATATTAACATTTACAGATCGACTATTTCCTTTAACC
TCCTAGAAGAAAGTTTTTGTGGGGAAAGATGATTCTGTATTATTCAGTAGCATAGACATTTTGCATATCAAAGATGT
TCATTTGGCACTAATGTTGATTGAAATCAAATCCATCTGAGATGCCTAGCTCGTATTTGCATTCTGGAAGCCTCCAT
CGCAGGGGAGCTCGGCAGGGTATGTGAGCTTTGTTGGAGGTGCGGTGTTTCATTCTGCAGCTGTTGTGAGGACAGAG
AGGCATGGCCCACAGGCAAAAAAAGTCACCACCCAGAAGATGCTCTGGGATAGAGGAACTGCTCCTTTTCATCAGCT
CTTCCAATGCCGTGGGAGAGGTGATCCCAGTCTTCTCTGTACATCTTGTGCTTTTCCATTAAGACTTGTTCCAGTGG
GAAGGAGCTTTGGAAAAATTGCAAAGGTCTGAATCTTCAGGGCATTTTCATGACAGGACTTGCCAATAATAATAATA
ATAATAATAATAATAATAATAATAATAAAGCTCCAGAGGCCTAACTGGTTTCTCAAGTCATTTCAGTGATATCATTG
AAACGTTTTTGTGGTACTTCCCTTTGTCTTTCACTGTTTCATTTTTATATTGCTTCATTTACTTCTTTGCTTTTGGC
TTTGTTATTAGAAAAAATAATTATGAGGTCTGTTGTGCATGTTGACTGTGATATTAAGTTATGGCATGCCATTAAGT
TTTCCAGACGATGTTGGATGTATCTGATTAGTTCATGTCATCTGTAAATACAATTCTTTTTTGTAGTACTTTGGAAT
GGAGCCTTTTTCTGGTGTACTGTATGCCATTTAAGTTTCACATACAAGCTGCTTTCGGCAAAGGCTTGAATATTTAT
AAATTTCAGATGGTTATCCTCACTTTATAGTACACTTAAGTGGCTACCATATATTTTTTATATGACAATTGGCTGAA
TAGCTGATGTGTATGACACTTTTACACAGATTTGCACTTTGGAACTATTTTATAGTTGTAATGCATCAATCAAATAC
ATTTCAAGCACATTTCTTGATCAATTTACCAGCAACCCTCTGAAGGAATGAAGGAGAGTTGTGATTGCTATGTCAAT
GAGTGAAATATACTTAAAAATGGCAGAGTTATATAGTACATTATTGTAGCAACCTTATATCTGATTTGAGATACTGT
GTTGCCAAATGTCCATGTTATGTTTATTTCTCTATTGGTTGTATTTATTAATTTTTAGAAGCCTTTAAACTGTGTTA
GAATCTTTTTGAAAAATGTTGATTTTGCATCATAAAGTTTCAATTTATCAAGGATATCTTTTCAGTTACACTTTTAG
AAAGAGTGAATAAAAAGGGCAGTGAGTTATGCTCTTGGACTTGGTGAAAGCTATCATCTCTCCATATTGTATTTGTT 538 CAGCTGGTTTAATTCACTCAGGTGGATGATTGCACATACATTGGAATTGGCTGGAGAGACTACACAGAGAAGTTTAA
TGATCGTGTACAATTTGAGGGTTGATGGTAGGGCTTTCTAAAAAAAGTAATATCAAGTGTGTTGTTAGTATTCATTT
AGTCATTTTTATTACTAATCTATAAATATATTTATTAAATTTGAAGATTAAATGGAATTATAAAGGAATATATTGGA
GGAAGTGTCAGTGTTGGTAATTATTCATCTATTTATCTGTCTATCATCAATATATATGGGTGCATGTCTGTGTATAT
TTGTGTGTATGTAAGTGTGCATGTGTATTATATGTTTGGGTAGAAAGAGATACATTGAATGGTATAAATCAATATAT
TTGAGCTAAGCAAGTTAAAAAAAAATCAGTTATCTTTGGGAACAGCAATCTATTATTGTTGTTTCCCTGAGTGCCAC
TTTAACTGTTTCACTCAATGGATGGTGGTTTATTCAGTTCAACACGTAATTTGATTTCTATTTTCTTAAAAGTAACC
ATGTTGGACTTACAAAGAGACTTAGAATGTCAGAGGTGTTAGGCAGATATTGGATACCAGTAAAATTGGCTGGATAT
GTCTGAAGGTCGGTGGAATTGTGAGAAAGACCAATGGTGATGGGGTTACATTGAAGAAAATATAAGATGAGCTAAAT
CAAAACCAGATTTGATTTTTTTGGGACTCCACCAGAAGTGGAAACTCATAAACAAGAGATGAAACAGAAAACTACAT
TTTTATTGATTGTATGAAGGAGTTAAATATATGGAGACATTTCCTCAGTGATGATCAAGGGTAGGTGGGGAAATTCC
AATAAGAATGTAGGATGACAATACCTTAGATATGTTGAAAACCAAGGAGGATGGGGATATAGTATCTTTCGTATTAT
AATAAGCATAAAGTTAGCAAAGGGACATTTAATTTGGTTAGC
<210> SEQ ID NO 44
<211> Length: 978
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 44
>Z25377_PEA_1_T7
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG
GTGGGGACTGGGCACATCATCAATACGATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTT
TAATGGGATTGTGGAAGAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCA
CACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTATTTAC
CGTGGTTTCTGGGCAGTCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGTGCAGC
CCCCTTCGCCAGCCATTTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAGGAATCTAGAAGATGGGGGGAT
GGAAGTGAAGTGGAATGTAAAAACGTCTGCCAGTGCCCCATGGTCTCCAACCCACTTTCAGATGCACCGTCTCATTT
CAACAGATATAGATGGAATTTCTTCTCTCTGTTACTCAAGCCTCTCAAAGTCCTTATTGTCCCAGCCTCTGCGTGAA
ACGTCTTCAGCCATCAATGACATCTCACTCCTTCAAGCCCTTATGCCACTGCTGGGATGGACCAGTCACTGGACCTG
CATTACAGTGGGCTTATATTGACCTTTACCTCTACACTTGTATATAACTCGTTTTCCCATTTAGTTGCAAGACACTT
GGAAGCACAGACCAAGGCTTACATTTGTGTTTTAATGTTTTTCTTGTAAATGCTTTATGCCTAAATGTTTCTGTACT
ACTCTTCTTTCCAAATCCTTATTGTTTAAAAGTTTCTCTCCTACTATACCATGCCTTATAAATATTGATTGAATGAA
TGGATGAAATGCATACCTGCTTATATTTCTAATTAAAGGCAATTTGGGATTATA
<210> SEQ ID NO 45 <211> Length: 708 <212> Type: DNA 539 <213> ORGANISM: Homo sapiens
<400> sequence: 45
>Z25377_PEA_1_T8
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG
GTGGGGACTGGGCACATCATCAATACGATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTT
TAATGGGATTGTGGAAGAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCA
CACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTAGTCTT
CTTTGATTCCTCATGGCAAACCAAATCCAGCAGCACATCAAAAAGCTTATCCACCATGATCAAGTGGGCTTCATCCC
TGGGATGCAAGGCTGGTTCAATATATGCAAATCAATAAATGTAATCCAGCATATAAACAGAACCAAAGACAAAAACC
ACATGATTATCTCAATAGATGCAGAAAAGGCCTTTGACAAAATTCAACAACACTTCATGCTAAAAACTCTCAATAAA
TTAGGTATTGACGGGATGTATCTCAAAATAATAAGAGCTATCTATGACAAACCCACAGCCAATATCATACTGAATGG
GCAAAAACTGGAAGCATTCCCTTTGAAAACTGGCAAAAGACAGGGATGCCCTCTCTCACCACTCCTATTCAACATAG
TGTTGGAAGTTCTGG
<210> SEQ ID NO 46
<211> Length: 783
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 46
>Z25377_PEA_1_T9
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG
GTGGGGACTGGGCACATCATCAATACGATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTT
TAATGGGATTGTGGAAGAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCA
CACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTATTTAC
CGTGGTTTCTGGGCAGTCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGTGCAGC
CCCCTTCGCCAGCCATTTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAGTTTCTGTGGGTCAAGAGTGTG
GAAGTGGCTAAGCAGAATGAGTCCAGCTCAGAATCCCATGAGTCTGCTAATCAAGCTATTTTCTGGGGTTGCAATCA
TCTGAAGGCCCAGCTGGGGCTAAAGAACGCACTTTGCAGCTCGCTTTTTGCCTGGCTCAGAAGATCCATTTCCAGAC
TCACTTACACTGGCAGGCCTCAGTTCCTTGCCATGTGAATCACTGGGATGGGCTGCCTGGACCTCCTCAGGATACAG
CAATTGCTAATAAAAGAGGTTTAAGGGGAACCAGAGAACTAGACGATAAAAGAAGTTGGCTAACATGAAAGCCCCAC
CTCCAACATTGGG
<210> SEQ ID NO 47
<211> Length: 730
<212> Type: DNA
<213> ORGANISM: Homo sapiens 54 0
<4 00> sequence : 4 7
>Z25377_PEA__1_T10
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG
GTGGGGACTGGGCACATCATCAATACGATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTT
TAATGGGATTGTGGAAGAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCA
CACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTAATGGA
ATTTCTTCTCTCTGTTACTCAAGCCTCTCAAAGTCCTTATTGTCCCAGCCTCTGCGTGAAACGTCTTCAGCCATCAA
TGACATCTCACTCCTTCAAGCCCTTATGCCACTGCTGGGATGGACCAGTCACTGGACCTGCATTACAGTGGGCTTAT
ATTGACCTTTACCTCTACACTTGTATATAACTCGTTTTCCCATTTAGTTGCAAGACACTTGGAAGCACAGACCAAGG
CTTACATTTGTGTTTTAATGTTTTTCTTGTAAATGCTTTATGCCTAAATGTTTCTGTACTACTCTTCTTTCCAAATC
CTTATTGTTTAAAAGTTTCTCTCCTACTATACCATGCCTTATAAATATTGATTGAATGAATGGATGAAATGCATACC
TGCTTATATTTCTAATTAAAGGCAATTTGGGATTATA
<210> SEQ ID NO 48
<211> Length: 1,193
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 48
>Z25377_PEA_1_T11
GAATCTGCCGGTGGGGCGTGAGCGAGAAGCCACCAAAACATGAGCTAGGACAGCCTTCTCAAGAAGATTCTGCCAAC
TCAAAAATATTATTCTTTTTTTTTTTTTTTTGCTGTTGTTTCTGAGAAACTAGGTGTCTTACCATTTTAAAATTTCA
TATTTTATTTAAAAGGAAACCAGTGAATTGAAAATGAGACTAAATATCGCTATCTTCTTTGGAGCTCTCTTTGGTGC
TTTGGGGGTGTTACTCTTTTTGGTGGCTTTTGGATCGGATTATTGGCTTCTTGCAACTGAAGTGGGGAGATGTTCAG
GTGAAAAGAATATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTTTAATGGGATTGTGGAA
GAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCACACATGCTTACCTGTC
TCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTATTTACCGTGGTTTCTGGGCAG
TCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGTGCAGCCCCCTTCGCCAGCCAT
TTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAGGAATCTAGAAGATGGGGGGATGGAAGTGAAGTGGAAT
GTAAAAACGTCTGCCAGTGCCCCATGGTCTCCAACCCACTTTCAGATGCACCGTCTCATTTCAACAGATATAGATGG
AATTTCTTCTCTCTGTTACTCAAGCCTCTCAAAGTCCTTATTGTCCCAGCCTCTGCGTGAAACGTCTTCAGCCATCA
ATGACATCTCACTCCTTCAAGCCCTTATGCCACTGCTGGGATGGACCAGTCACTGGACCTGCATTACAGTGGGCTTA
TATTGACCTTTACCTCTACACTTGTATATAACTCGTTTTCCCATTTAGTTGCAAGACACTTGGAAGCACAGACCAAG
GCTTACATTTGTGTTTTAATGTTTTTCTTGTAAATGCTTTATGCCTAAATGTTTCTGTACTACTCTTCTTTCCAAAT
CCTTATTGTTTAAAAGTTTCTCTCCTACTATACCATGCCTTATAAATATTGATTGAATGAATGGATGAAATGCATAC
CTGCTTATATTTCTAATTAAAGGCAATTTGGGATTATA 541 <210> SEQ ID NO 49
<211> Length: 998
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 49
>Z25377_PEA_1_T12
GAATCTGCCGGTGGGGCGTGAGCGAGAAGCCACCAAAACATGAGCTAGGACAGCCTTCTCAAGAAGATTCTGCCAAC
TCAAAAATATTATTCTTTTTTTTTTTTTTTTGCTGTTGTTTCTGAGAAACTAGGTGTCTTACCATTTTAAAATTTCA
TATTTTATTTAAAAGGAAACCAGTGAATTGAAAATGAGACTAAATATCGCTATCTTCTTTGGAGCTCTCTTTGGTGC
TTTGGGGGTGTTACTCTTTTTGGTGGCTTTTGGATCGGATTATTGGCTTCTTGCAACTGAAGTGGGGAGATGTTCAG
GTGAAAAGAATATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTTTAATGGGATTGTGGAA
GAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCACACATGCTTACCTGTC
TCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTATTTACCGTGGTTTCTGGGCAG
TCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGTGCAGCCCCCTTCGCCAGCCAT
TTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAGTTTCTGTGGGTCAAGAGTGTGGAAGTGGCTAAGCAGA
ATGAGTCCAGCTCAGAATCCCATGAGTCTGCTAATCAAGCTATTTTCTGGGGTTGCAATCATCTGAAGGCCCAGCTG
GGGCTAAAGAACGCACTTTGCAGCTCGCTTTTTGCCTGGCTCAGAAGATCCATTTCCAGACTCACTTACACTGGCAG
GCCTCAGTTCCTTGCCATGTGAATCACTGGGATGGGCTGCCTGGACCTCCTCAGGATACAGCAATTGCTAATAAAAG
AGGTTTAAGGGGAACCAGAGAACTAGACGATAAAAGAAGTTGGCTAACATGAAAGCCCCACCTCCAACATTGGG
<210> SEQ ID NO 50
<211> Length: 1,083
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 50
>Z25377_PEA_1_T13
GAATCTGCCGGTGGGGCGTGAGCGAGAAGCCACCAAAACATGAGCTAGGACAGCCTTCTCAAGAAGATTCTGCCAAC
TCAAAAATATTATTCTTTTTTTTTTTTTTTTGCTGTTGTTTCTGAGAAACTAGGTGTCTTACCATTTTAAAATTTCA
TATTTTATTTAAAAGGAAACCAGTGAATTGAAAATGAGACTAAATATCGCTATCTTCTTTGGAGCTCTCTTTGGTGC
TTTGGGGGTGTTACTCTTTTTGGTGGCTTTTGGATCGGATTATTGGCTTCTTGCAACTGAAGTGGGGAGATGTTCAG
GTGAAAAGAATATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTTTAATGGGATTGTGGAA
GAGAATGACTCCAATATTTGGAAGTTCTGGTACACCAATCAGCCACCGTCCAAGAACTGCACACATGCTTACCTGTC
TCCGTACCCCTTCATGAGAGGCGAGCACAACTCGACCTCCTATGACTCTGCAGTTATTTACCGTGGTTTCTGGGCAG
TCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGTGCAGCCCCCTTCGCCAGCCAT
TTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAGATGGAATTTCTTCTCTCTGTTACTCAAGCCTCTCAAA
GTCCTTATTGTCCCAGCCTCTGCGTGAAACGTCTTCAGCCATCAATGACATCTCACTCCTTCAAGCCCTTATGCCAC 542 TGCTGGGATGGACCAGTCACTGGACCTGCATTACAGTGGGCTTATATTGACCTTTACCTCTACACTTGTATATAACT
CGTTTTCCCATTTAGTTGCAAGACACTTGGAAGCACAGACCAAGGCTTACATTTGTGTTTTAATGTTTTTCTTGTAA
ATGCTTTATGCCTAAATGTTTCTGTACTACTCTTCTTTCCAAATCCTTATTGTTTAAAAGTTTCTCTCCTACTATAC
CATGCCTTATAAATATTGATTGAATGAATGGATGAAATGCATACCTGCTTATATTTCTAATTAAAGGCAATTTGGGA
TTATA
<210> SEQ ID NO 51
<211> Length: 8,921
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 51
>HSACMHCP_PEA_1_T2
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG
ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT
CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA
AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC
TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC
CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA
AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC
GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG
AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA
ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC
TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA
TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT
ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG
GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA
TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT
TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC
ATCGCTGGCTTCGAGATCTTCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCA
GTTCTTCAACCACCACATGTTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACT
TTGGCATGGACCTGCAGGCCTGCATTGACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGC
ATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCA
GAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACA
TCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAG 543 CTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAA
GGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCC
ATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCAC
CAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGA
CTTCCGGCAGAGGTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAG
AGAAGCTGCTCAGCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGG
CTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGG
CCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGG
CCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACG
GAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAA
GGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACA
ACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATG
AATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTC
AGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACA
AGGTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTA
CAAGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGT
CAAGCTGGAGCAGCAGGTGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAG
CAAAGCGGAAACTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTG
GAAGAAAAGCTTAAGAAGAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCT
TCAACTACAGAAGAAACTGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCG
CCAGGGCTAAGGTGGAGAAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCC
GGCGGGGCCACGTCCGTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGA
GGAGGCCACGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCG
AGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGAC
GTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGC
CAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGA
CCGAGAATGGAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCT
TATACCCAGCAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACT
GCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGC
GCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAG
GAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAA
GTGCTCCTCACTGGAGAAGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCA
ATGCTGCTGCTGCAGCCCTGGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAG
GAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGC
CTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGAGGAAATCTCGGACCTTA
CTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAGCTGGAGGTGGAGAAGCTG
GAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGCCTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTAGA
GTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACC 544 ACCAGCGGGTGGTGGACTCGCTGCAGACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAG
AAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAA
GCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGGACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACC
TGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTG
GAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTC
CCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAGTCGGAAGTGGAGGAGG
CAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCACGGATGCCGCCATGATGGCAGAGGAGCTG
AAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAACATGGAGCAGACCATTAAGGACCTGCAGCA
CCGGCTGGACGAGGCCGAGCAGATCGCCCTCAAGGGAGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGG
AGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGC
ATCAAGGAGCTCACCTACCAGGTGCGGCGGACGCCAGACACCGGGAGTAGATGTGGAAGTTTCTTCTCTGGCCCCAC
TGCCCCGCCCTCACAGGGCTCCTCTCACCTCCTCCTTGAGATGCTGTTGGTAGATTTAACGTTCTTCTCACGCTCTG
CAGTCAGTTTGACTTGAGTCTATGAGTTTTTCCAGCAAATGAAGAATCTACTTCTACTTCCTGAAAACTCTTCTAAC
TAGTCTTTCCCCAGGTTTCTTTCTTTCTTTTTTTTTTTTTTTAATAACTCTAAGTGCTACCATGAAGACTTCAGAAC
AGTTCAAAGAATCCTTCCACCTTCGACTGTGGGGATAAGAGTCAGGGGAGGGGAAAAGACCCGGAAATCTTCCATAG
AACTTCTGGCACACAAAGAGAAGGCCACAGAGAAAGAGGACCCTAGAATGCTCTAAAACCTCCACTTGCATAGCTGA
GAGCTGTGCCCTTGGCCCGTTATTTTCAGTGTACCTGGGAAGAAAAGGCCAAGGAGACGAGGGTGTCAGTCCATTTG
ATAGATGGATACCAGAGGCACAAGAAAGAGGTTACAGATACAGAACCACAGAGTGATTTGTGGACAGAAGTAGAAAT
GGCATCCTGGCACATACAATGATAAAGAGATAGGAATGATCGAGTGACGTTGGAGCCAGTGATCCCGATGCCTGAAT
TCTGGCCCAGTACAATATATTAGAATGTAGAATAATCTGGATTATGATAATACCCCCTTCTTTCTGCATTCTTTTTC
TGGTCAAGAACTACTGGCCAAGAGAACCTATGTAAGTCCAGGTTGGAGCTTTATCCACCATACTGGAGCTGGAACAG
ACCTGGTGCTTTTATATTACCACATTAGGGAATTCCATTAGGTTCTGAGCCCCTCCCCCTACTTCTAGCTTTATGAC
TTCAGCCTTCATTGCTCTGTGGATCCCTGACTGACAACCTTGCATTGCCCCTTTGACCTACGATAGAGTCAGAGAAT
CTTCCCCACCACCTCTTTGACCTGGATCATTGCAGGGAGGGGCAGCAAAGGCAAGGGGAGAAGAGTAAAATGATGGA
GGAGGGAAAGGTGATTGCATTTGCTCCCCCTCCAAACCAGCTTCTCCCACCCTCCCACCCCCAGACAGAGGAAGACA
AAAAGAACCTGCTGCGGCTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCGAG
GAGGCGGAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCG
GGCGGACATCGCTGAGTCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCACG
ATGAGGAGTGACACTGCCTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCAAACTCTGCCTGAGCC
CATCTGTCCTTCCTGCCAGCTGTCCATCCTGGATCAGGGCAGTAGGGGGCCTGAGAGGAGGGAGGCCCCCAGCCCCT
GTATCAGAGCTGCCAGAGCCAAGGCATCCCATATCCACAAGGAAGGAGACCGAGGTGCAGAGGAGTGAGGTGTTCTG
CCTGACGTGGACAGCTGTGAGTCCCAGTTCTGCTCAGTCAACCACACAAGGGTGGAGAGGGAGAAATTTCAAAAGTG
AAGAAAACAATGGCATCAAAATGGTGAGCCAGTCCAAGATGCTACGAGATAGAATTTTGGTGCCGAAGTTGAAGCCA
CTCTCCACCTACCCCACCCCTGAGGCTGCAATGATTAAAGGTGTCCTAGGACACCCATTCTTTCTGAAATGAATTTT
CCACCAATGCCAGAAAAGGCTCAGAGCTGGCTGAGAATTAAGGTATGGGAAAGGAGATGGGAGAGATTCCATTCTAG
TCAGCCCCTAGGAAGTAACTCCCAGGGAGCCCCCTCCCTGTCTTCCCCAGGGGTCTCCCCCTGCCTCCTATGATTCA
GCACCTCACCGTGAGGGCATCTTGAGACTCTGGGGCCAATCAACACTGAGCCCAAACCAATATGCCATGAGGACCAA
GCCTGGGCATTGCTCATTTCATGTTGGTTCTCACACAGACACAGATGGCACAGGTGCCTGTACAGGGAAACACTGTG 545 GTCACATTTCTGCTCTCTCTAAGCTCCTACTGGGGACAGTCTGGCCTGGATCACACAGCTGCTTGTGGGACAGGCCC
GGTCCTGACCCCGTTCTGCACAAAGCAAATCCCCACTCCCCACTGGGCTTTGCAGCCAGGCTCTGCTGACCGCCTCC
TTAACCGTTCACCTGGCACCCCATCTCCCTGACTCCCCAAGTGGAGCCTCTTCTATCCCTCCTCTGAGACCATGAGA
ATGGACTGTGCATAAAGCCCTGAGAAATGTGAGCAGTGACCAGAGAAACACAAAATCCTGTTGGTTCTAGCCCAGGA
GAGGCTGCCAGTTCTGATGGTGAGCCAGGACACAAGGATAGGAGAACAGGAAGCAGGAGGCAGGAAAAAGACCAAGA
GAGAGGAGTGGCTGCCACCAAGGAAGCAGAGCGCTCTGACCAGAGTTCAAGATCCAGGGTTCGGGCAGGACTTGGGA
GCTGGGGCCTGCAGCTGGAAGGAGCGCTCCAGAAGAAGGATTGTATCTCAGGGCGGGAACACACACACATCAGCGAC
AGGAGATAGCACGTCAGCTGGGATGGAGCTGCTGAGCCAGGCCATGCTGGGCTCCTCGGGCTGGGCAGGAACGTCTG
GCTGCACATCTGTCTGTCTCGGCCCAGCAGGGCTGACTCCCGGGCTGTGGCAGTGTCTGCTCCAAACTCCCCTGGGC
CTTCCCATAGCATTCACTGTGGGGAGCTCTTGACCAGCTTGTCTCTTTCCCAGCCTGTGAGTGCTAAAGGGCAGGCC
CCCCGTCACCTCTGAGGCCCTGGCACCCAGCACAGTGTGCATGGGAGATGCTCAGGAAATGTGTGCTGAGGAGCTGG
CAAGCTGGGAGGGTGGACCCGCAGTGGAGGGAAGAGTTGGCCATTCTTTTCTGAGCTACAAGGAGGCTCAGTACAGT
ATCCAGAACACTCGCTTAGGTGTCAGAAGAGCTGCGTTCTGGCCCTAGCTCTGTCACAAATGAGTTCACCTCCCCTG
GCTGGGCCTGTTTTCTCTTATGTGAAATGAGGGCATTGGACCAGCTGATAATCAACGGCTCTCCCAGCATTCGCATT
TTGGGAAATCTCTCCCTCCTCTGATACCTCAGGCTGCCCTCTCCCTGCCTCCTGTTCCTGTCATAG
<210> SEQ ID NO 52
<211> Length: 6,290
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 52
>HSACMHCP_PEA_1_T3
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG
ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT
CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA
AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC
TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC
CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA
AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC
GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG
AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA
ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC
TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA
TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT 546 ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG
GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA
TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT
TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC
ATCGCTGGCTTCGAGATCTTCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCA
GTTCTTCAACCACCACATGTTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACT
TTGGCATGGACCTGCAGGCCTGCATTGACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGC
ATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCA
GAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACA
TCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAG
CTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAA
GGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCC
ATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCAC
CAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGA
CTTCCGGCAGAGGTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAG
AGAAGCTGCTCAGCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGG
CTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGG
CCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGG
CCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACG
GAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAA
GGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACA
ACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATG
AATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTC
AGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACA
AGGTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTA
CAAGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGT
CAAGCTGGAGCAGCAGGTGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAG
CAAAGCGGAAACTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTG
GAAGAAAAGCTTAAGAAGAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCT
TCAACTACAGAAGAAACTGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCG
CCAGGGCTAAGGTGGAGAAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCC
GGCGGGGCCACGTCCGTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGA
GGAGGCCACGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCG
AGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGAC
GTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGC
CAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGA
CCGAGAATGGAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCT
TATACCCAGCAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGTGAGGCCCAGTGGGGAGGGTGGGCA 547 GGCTTGATGGCAGCCCTGGGGCAATTCATCTCAGTGCCAGAAATGGAGCCTGGAGCTGGAAAGAGTCCTCTGCAAGG
GAAAGACCCTCCAGTCTAGGTTCTGCCCTGCAGCTAAGCGTCATTTAATGCCTCTTTTCTTATTCGTAAGGGGATGG
GGTGAGCAGACTGGGAAACTCCTCAAACAGTGAGGTGCCACATCAGCCCACATGGTGAATAAGGCTGGGCTTGGTTG
AAGTACTACATAAGAAGAGAATCTAGAGAATGGGGCACAGGGAGTCCCTCCCACCTCCTGGTGCCCCCCCCCCTCCC
CAGGCGAAGAACGCCCTGGCCCATGCACTGCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGA
GGAGACAGAGGCCAAGGCCGAGCTGCAGCGCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGT
ATGAGACGGACGCCATTCAGCGGACTGAGGAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCAGCGGCTGCAGGATGCC
GAGGAGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCACTGGAGAAGACCAAGCACCGGCTACAGAATGAGATAGA
GGACTTGATGGTGGACGTAGAGCGCTCCAATGCTGCTGCTGCAGCCCTGGACAAGAAGCAGAGAAACTTTGACAAGA
TCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCTC
AGCACAGAGCTCTTCAAGCTCAAGAACGCCTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACAA
GAACCTTCAGGAGGAAATCTCGGACCTTACTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGG
TCCGCAAACAGCTGGAGGTGGAGAAGCTGGAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGCCTCCCTGGAGCACGAG
GAGGGCAAGATCCTCCGGGCCCAGCTAGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAAGGA
CGAGGAGATGGAACAGGCCAAGCGCAACCACCAGCGGGTGGTGGACTCGCTGCAGACCTCCCTGGATGCAGAGACAC
GCAGCCGCAACGAGGTCCTGAGGGTGAAGAAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCAC
GCCAACCGCATGGCCGCCGAGGCCCAGAAGCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGGACACCCAGATCCAGCT
GGACGATGCGGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGG
CTGAGCTGGAGGAGCTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAG
ACCAGCGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCT
GACCCAGCTCCAGTCGGAAGTGGAGGAGGCAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCA
CGGATGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAAC
ATGGAGCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCGAGCAGATCGCCCTCAAGGGAGGCAAGAAGCA
GCTGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGG
TGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGACAGAGGAAGACAAAAAGAACCTGCTG
CGGCTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCA
AGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCTG
AGTCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCACGATGAGGAGTGACAC
TGCCTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCAAACTC
<210> SEQ ID NO 53
<211> Length: 6,057
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 53
>HSACMHCP_PEA_1_T4
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG 548 ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT
CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA
AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC
TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC
CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA
AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC
GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG
AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA
ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC
TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA
TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT
ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG
GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA
TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT
TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC
ATCGCTGGCTTCGAGATCTTCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCA
GTTCTTCAACCACCACATGTTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACT
TTGGCATGGACCTGCAGGCCTGCATTGACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGC
ATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCA
GAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACA
TCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAG
CTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAA
GGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCC
ATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCAC
CAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGA
CTTCCGGCAGAGGTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAG
AGAAGCTGCTCAGCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGG
CTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGG
CCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGG
CCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACG
GAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAA
GGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACA
ACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATG
AATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTC
AGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACA 549 AGGTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTA
CAAGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGT
CAAGCTGGAGCAGCAGGTGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAG
CAAAGCGGAAACTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTG
GAAGAAAAGCTTAAGAAGAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCT
TCAACTACAGAAGAAACTGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCG
CCAGGGCTAAGGTGGAGAAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCC
GGCGGGGCCACGTCCGTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGA
GGAGGCCACGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCG
AGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGAC
GTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGC
CAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGA
CCGAGAATGGAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCT
TATACCCAGCAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACT
GCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGC
GCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAG
GAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAA
GTGCTCCTCACTGGAGAAGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCA
ATGCTGCTGCTGCAGCCCTGGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAG
GAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGC
CTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGGTGTGCTGGGGGTCCAAG
AGGCCAGAGATGAGTTGGTGGGAGGGAGGGCCATGCAGGGGCAGGGGGAACATAGGCTTTGAGCTTTCTGGCCCTCT
GGTCCCCAGAGGAAATCTCGGACCTTACTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGGTC
CGCAAACAGCTGGAGGTGGAGAAGCTGGAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGCCTCCCTGGAGCACGAGGA
GGGCAAGATCCTCCGGGCCCAGCTAGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAAGGACG
AGGAGATGGAACAGGCCAAGCGCAACCACCAGCGGGTGGTGGACTCGCTGCAGACCTCCCTGGATGCAGAGACACGC
AGCCGCAACGAGGTCCTGAGGGTGAAGAAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCACGC
CAACCGCATGGCCGCCGAGGCCCAGAAGCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGGACACCCAGATCCAGCTGG
ACGATGCGGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGGCT
GAGCTGGAGGAGCTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGAC
CAGCGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCTGA
CCCAGCTCCAGTCGGAAGTGGAGGAGGCAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCACG
GATGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAACAT
GGAGCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCGAGCAGATCGCCCTCAAGGGAGGCAAGAAGCAGC
TGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTG
AAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGACAGAGGAAGACAAAAAGAACCTGCTGCG
GCTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCAAG
CCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCTGAG 550 TCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCACGATGAGGAGTGACACTG
CCTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCAAACTC
<210> SEQ ID NO 54
<211> Length: 6,177
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 54
>HSACMHCP_PEA_1_T6
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG
ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT
CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA
AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC
TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC
CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA
AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC
GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG
AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA
ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC
TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA
TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT
ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG
GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA
TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT
TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC
ATCGCTGGCTTCGAGATCTTCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCA
GTTCTTCAACCACCACATGTTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACT
TTGGCATGGACCTGCAGGCCTGCATTGACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGC
ATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCA
GAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACA
TCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAG
CTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAA
GGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCC
ATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCAC 551 CAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGA
CTTCCGGCAGAGGTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAG
AGAAGCTGCTCAGCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGG
CTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGG
CCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGG
CCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACG
GAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAA
GGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACA
ACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATG
AATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTC
AGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACA
AGGTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTA
CAAGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGT
CAAGCTGGAGCAGCAGGTGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAG
CAAAGCGGAAACTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTG
GAAGAAAAGCTTAAGAAGAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCT
TCAACTACAGAAGAAACTGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCG
CCAGGGCTAAGGTGGAGAAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCC
GGCGGGGCCACGTCCGTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGA
GGAGGCCACGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCG
AGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGAC
GTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGC
CAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGA
CCGAGAATGGAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCT
TATACCCAGCAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACT
GCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGC
GCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAG
GAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAA
GTGCTCCTCACTGGAGAAGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCA
ATGCTGCTGCTGCAGCCCTGGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAG
GAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGC
CTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGAGGAAATCTCGGACCTTA
CTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAGCTGGAGGTGGAGAAGCTG
GAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGCCTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTAGA
GTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACC
ACCAGCGGGTGGTGGACTCGCTGCAGACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAG
AAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAA
GCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGGACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACC 552
TGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTG
GAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTC CCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAGTCGGAAGTGGAGGAGG CAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCACGGATGCCGCCATGATGGCAGAGGAGCTG AAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAACATGGAGCAGACCATTAAGGACCTGCAGCA CCGGCTGGACGAGGCCGAGCAGATCGCCCTCAAGGGAGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGG AGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGC ATCAAGGAGCTCACCTACCAGGTGCGGCGGACGCCAGACACCGGGAGTAGATGTGGAAGTTTCTTCTCTGGCCCCAC TGCCCCGCCCTCACAGGGCTCCTCTCACCTCCTCCTTGAGATGCTGTTGGTAGATTTAACGTTCTTCTCACGCTCTG CAGTCAGTTTGACTTGAGTCTATGAGTTTTTCCAGCAAATGAAGAATCTACTTCTACTTCCTGAAAACTCTTCTAAC TAGTCTTTCCCCAGACAGAGGAAGACAAAAAGAACCTGCTGCGGCTACAGGACCTGGTGGACAAGCTGCAACTGAAG GTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCA GCATGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCTGAGTCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTG ACATTGGTGCCAAGCAAAAAATGCACGATGAGGAGTGACACTGCCTCGGGAACCTCACTCTTGCCAACCTGTAATAA ATATGAGTGCCAAACTC
<210> SEQ ID NO 55
<211> Length: 9,119 '
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 55
>HSACMHCP_PEA_1_T7
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG
ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT
CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA
AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC
TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC
CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA
AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC
GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG
AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA
ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC
TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA
TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT 553 ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG
GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA
TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT
TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC
ATCGCTGGCTTCGAGATCTTCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCA
GTTCTTCAACCACCACATGTTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACT
TTGGCATGGACCTGCAGGCCTGCATTGACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGC
ATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCA
GAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACA
TCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAG
CTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAA
GGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCC
ATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCAC
CAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGA
CTTCCGGCAGAGGTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAG
AGAAGCTGCTCAGCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGG
CTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGG
CCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGG
CCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACG
GAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAA
GGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACA
ACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATG
AATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTC
AGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACA
AGGTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTA
CAAGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGT
CAAGCTGGAGCAGCAGGTGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAG
CAAAGCGGAAACTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTG
GAAGAAAAGCTTAAGAAGAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCT
TCAACTACAGAAGAAACTGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCG
CCAGGGCTAAGGTGGAGAAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCC
GGCGGGGCCACGTCCGTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGA
GGAGGCCACGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCG
AGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGAC
GTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGC
CAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGA
CCGAGAATGGAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCT
TATACCCAGCAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACT 554 GCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGC
GCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAG
GAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAA
GTGCTCCTCACTGGAGAAGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCA
ATGCTGCTGCTGCAGCCCTGGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAG
GAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGC
CTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGAGGAAATCTCGGACCTTA
CTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAGCTGGAGGTGGAGAAGCTG
GAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGCCTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTAGA
GTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACC
ACCAGCGGGTGGTGGACTCGCTGCAGACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAG
AAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAA
GCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGGACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACC
TGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTG
GAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTC
CCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAGTCGGAAGTGGAGGAGG
CAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCACGGATGTAAGTGACCGCCCACCTTCCGCC
TCCCCTAAAGACAGAAACAAGGCCTTGGGTCCAGGCCAGGCCACTGTGCTGTAACACCAAGCCAACTCTGCAGTTCT
GTGGATTTGAGGGCCTGATGGGAGAAAGGAGATCCTTGGGGGGCAAAAGGCCCCGGCCCCTGGCCCATGTTCCTTGC
CACCTCTCTCCTGCACACAGGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAG
CGCATGAAGAAGAACATGGAGCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCGAGCAGATCGCCCTCAA
GGGAGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGC
GCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGGTGCGGCGGACG
CCAGACACCGGGAGTAGATGTGGAAGTTTCTTCTCTGGCCCCACTGCCCCGCCCTCACAGGGCTCCTCTCACCTCCT
CCTTGAGATGCTGTTGGTAGATTTAACGTTCTTCTCACGCTCTGCAGTCAGTTTGACTTGAGTCTATGAGTTTTTCC
AGCAAATGAAGAATCTACTTCTACTTCCTGAAAACTCTTCTAACTAGTCTTTCCCCAGGTTTCTTTCTTTCTTTTTT
TTTTTTTTTAATAACTCTAAGTGCTACCATGAAGACTTCAGAACAGTTCAAAGAATCCTTCCACCTTCGACTGTGGG
GATAAGAGTCAGGGGAGGGGAAAAGACCCGGAAATCTTCCATAGAACTTCTGGCACACAAAGAGAAGGCCACAGAGA
AAGAGGACCCTAGAATGCTCTAAAACCTCCACTTGCATAGCTGAGAGCTGTGCCCTTGGCCCGTTATTTTCAGTGTA
CCTGGGAAGAAAAGGCCAAGGAGACGAGGGTGTCAGTCCATTTGATAGATGGATACCAGAGGCACAAGAAAGAGGTT
ACAGATACAGAACCACAGAGTGATTTGTGGACAGAAGTAGAAATGGCATCCTGGCACATACAATGATAAAGAGATAG
GAATGATCGAGTGACGTTGGAGCCAGTGATCCCGATGCCTGAATTCTGGCCCAGTACAATATATTAGAATGTAGAAT
AATCTGGATTATGATAATACCCCCTTCTTTCTGCATTCTTTTTCTGGTCAAGAACTACTGGCCAAGAGAACCTATGT
AAGTCCAGGTTGGAGCTTTATCCACCATACTGGAGCTGGAACAGACCTGGTGCTTTTATATTACCACATTAGGGAAT
TCCATTAGGTTCTGAGCCCCTCCCCCTACTTCTAGCTTTATGACTTCAGCCTTCATTGCTCTGTGGATCCCTGACTG
ACAACCTTGCATTGCCCCTTTGACCTACGATAGAGTCAGAGAATCTTCCCCACCACCTCTTTGACCTGGATCATTGC
AGGGAGGGGCAGCAAAGGCAAGGGGAGAAGAGTAAAATGATGGAGGAGGGAAAGGTGATTGCATTTGCTCCCCCTCC
AAACCAGCTTCTCCCACCCTCCCACCCCCAGACAGAGGAAGACAAAAAGAACCTGCTGCGGCTACAGGACCTGGTGG 555 ACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCAAGCCAACACCAACCTGTCC
AAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCTGAGTCCCAGGTCAACAAGCT
TCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCACGATGAGGAGTGACACTGCCTCGGGAACCTCACTC
TTGCCAACCTGTAATAAATATGAGTGCCAAACTCTGCCTGAGCCCATCTGTCCTTCCTGCCAGCTGTCCATCCTGGA
TCAGGGCAGTAGGGGGCCTGAGAGGAGGGAGGCCCCCAGCCCCTGTATCAGAGCTGCCAGAGCCAAGGCATCCCATA
TCCACAAGGAAGGAGACCGAGGTGCAGAGGAGTGAGGTGTTCTGCCTGACGTGGACAGCTGTGAGTCCCAGTTCTGC
TCAGTCAACCACACAAGGGTGGAGAGGGAGAAATTTCAAAAGTGAAGAAAACAATGGCATCAAAATGGTGAGCCAGT
CCAAGATGCTACGAGATAGAATTTTGGTGCCGAAGTTGAAGCCACTCTCCACCTACCCCACCCCTGAGGCTGCAATG
ATTAAAGGTGTCCTAGGACACCCATTCTTTCTGAAATGAATTTTCCACCAATGCCAGAAAAGGCTCAGAGCTGGCTG
AGAATTAAGGTATGGGAAAGGAGATGGGAGAGATTCCATTCTAGTCAGCCCCTAGGAAGTAACTCCCAGGGAGCCCC
CTCCCTGTCTTCCCCAGGGGTCTCCCCCTGCCTCCTATGATTCAGCACCTCACCGTGAGGGCATCTTGAGACTCTGG
GGCCAATCAACACTGAGCCCAAACCAATATGCCATGAGGACCAAGCCTGGGCATTGCTCATTTCATGTTGGTTCTCA
CACAGACACAGATGGCACAGGTGCCTGTACAGGGAAACACTGTGGTCACATTTCTGCTCTCTCTAAGCTCCTACTGG
GGACAGTCTGGCCTGGATCACACAGCTGCTTGTGGGACAGGCCCGGTCCTGACCCCGTTCTGCACAAAGCAAATCCC
CACTCCCCACTGGGCTTTGCAGCCAGGCTCTGCTGACCGCCTCCTTAACCGTTCACCTGGCACCCCATCTCCCTGAC
TCCCCAAGTGGAGCCTCTTCTATCCCTCCTCTGAGACCATGAGAATGGACTGTGCATAAAGCCCTGAGAAATGTGAG
CAGTGACCAGAGAAACACAAAATCCTGTTGGTTCTAGCCCAGGAGAGGCTGCCAGTTCTGATGGTGAGCCAGGACAC
AAGGATAGGAGAACAGGAAGCAGGAGGCAGGAAAAAGACCAAGAGAGAGGAGTGGCTGCCACCAAGGAAGCAGAGCG
CTCTGACCAGAGTTCAAGATCCAGGGTTCGGGCAGGACTTGGGAGCTGGGGCCTGCAGCTGGAAGGAGCGCTCCAGA
AGAAGGATTGTATCTCAGGGCGGGAACACACACACATCAGCGACAGGAGATAGCACGTCAGCTGGGATGGAGCTGCT
GAGCCAGGCCATGCTGGGCTCCTCGGGCTGGGCAGGAACGTCTGGCTGCACATCTGTCTGTCTCGGCCCAGCAGGGC
TGACTCCCGGGCTGTGGCAGTGTCTGCTCCAAACTCCCCTGGGCCTTCCCATAGCATTCACTGTGGGGAGCTCTTGA
CCAGCTTGTCTCTTTCCCAGCCTGTGAGTGCTAAAGGGCAGGCCCCCCGTCACCTCTGAGGCCCTGGCACCCAGCAC
AGTGTGCATGGGAGATGCTCAGGAAATGTGTGCTGAGGAGCTGGCAAGCTGGGAGGGTGGACCCGCAGTGGAGGGAA
GAGTTGGCCATTCTTTTCTGAGCTACAAGGAGGCTCAGTACAGTATCCAGAACACTCGCTTAGGTGTCAGAAGAGCT
GCGTTCTGGCCCTAGCTCTGTCACAAATGAGTTCACCTCCCCTGGCTGGGCCTGTTTTCTCTTATGTGAAATGAGGG
CATTGGACCAGCTGATAATCAACGGCTCTCCCAGCATTCGCATTTTGGGAAATCTCTCCCTCCTCTGATACCTCAGG
CTGCCCTCTCCCTGCCTCCTGTTCCTGTCATAG
<210> SEQ ID NO 56
<211> Length: 5,395
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 56
>HSACMHCP_PEA_1_T8
CCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATCCGGGGCGGGGAAGACTGTG
AACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCAAGAAGGACAATGCCAATGC 556 GAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTCGGCAATGCCAAGACTGTCC
GGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGGAAAGCTGGCTTCTGCAGAC
ATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAAACTACCACATCTTCTACCA
GATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCCTACGACTACGCCTTCGTGT
CTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGATAGTGCCTTTGACGTGCTG
GGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACTACGGGAACATGAAGTTCAA
GCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCGGCCTACCTCATGGGGCTGA
ACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTATGTCACCAAGGGGCAGAGC
GTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGTTCAACTGGATGGTGACGCG
CATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGACATCGCTGGCTTCGAGATCT
TCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCAGTTCTTCAACCACCACATG
TTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACTTTGGCATGGACCTGCAGGC
CTGCATTGACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGCATGTTCCCCAAGGCCACTG
ACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCAGAAGCCACGCAACATCAAG
GGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACATCCTGGGCTGGCTGGAAAA
AAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAGCTCATGGCCACTCTCTTCT
CCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAAGGGCTCATCCTTCCAGACG
GTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCCATCCTCACTTTGTGCGTTG
CATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCACCAGCTGCGCTGCAATGGCG
TGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGACTTCCGGCAGAGGTATCGC
ATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAGAGAAGCTGCTCAGCTCTCT
GGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGGCTGCTTGGGCTGCTGGAGG
AGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGGCCAGCTCATGCGCATTGAG
TTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATGGGGGTCAAGAA
TTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACGGAGAAGGAGATGGCCACCA
TGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAAGGAGCTGGAGGAGAAGATG
GTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACAACCTCAATGATGCTGAGGA
GCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATGAATGAGAGGCTGGAGGATG
AGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTCAGAGCTCAAGAAGGACATT
GATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACAAGGTGAAGAACCTAACAGA
GGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTACAAGAGGCCCATCAGCAGG
CCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGTCAAGCTGGAGCAGCAGGTG
GATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAGCAAAGCGGAAACTGGAGGG
CGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTGGAAGAAAAGCTTAAGAAGA
AGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCTTCAACTACAGAAGAAACTG
AAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCGCCAGGGCTAAGGTGGAGAA
GCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCCGGCGGGGCCACGTCCGTGC
AGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCACGCTGCAGCAC 557 GAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCGAGCAGATCGACAACCTGCA
GCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGACGTCACCTCCAACATGGAGC
AGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGCCAATGAGTACCGCGTGAAG
CTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGACCGAGAATGGAGAGTTGGC
CCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCTTATACCCAGCAAATGGAGG
ACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACTGCAGTCGGCCCGGCATGAC
TGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGCGCGTCCTGTCCAAGGCCAA
CTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAGGAGCTCGAAGAGGCCAAAA
AGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCACTGGAGAAG
ACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCAATGCTGCTGCTGCAGCCCT
GGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCTGAGCTGG
AGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGCCTACGAGGAGTCCCTGGAG
CACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGAGGAAATCTCGGACCTTACTGAGCAGCTAGGAGAAGG
AGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAGCTGGAGGTGGAGAAGCTGGAGCTGCAGTCAGCCCTGG
AGGAGGCAGAGGCCTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTAGAGTTCAACCAGATCAAGGCA
GAGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACCACCAGCGGGTGGTGGACTC
GCTGCAGACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAGAAGAAGATGGAAGGAGACC
TCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAAGCAAGTCAAGAGCCTCCAG
AGCTTGCTGAAGGACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCCAT
CGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCC
GGAAGCTGGCGGAGCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCATC
AACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAGTCGGAAGTGGAGGAGGCAGTGCAGGAGTGCAGAAA
CGCCGAGGAGAAGGCCAAGAAGGCCATCACGGATGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCA
GCGCCCACCTGGAGCGCATGAAGAAGAACATGGAGCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCGAG
CAGATCGCCCTCAAGGGAGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGA
GGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACC
AGACAGAGGAAGACAAAAAGAACCTGCTGCGGCTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTAC
AAGCGCCAGGCCGAGGAGGCGGAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGA
TGAGGCAGAGGAGCGGGCGGACATCGCTGAGTCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCA
AGCAAAAAATGCACGATGAGGAGTGACACTGCCTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCA
AACTC
<210> SEQ ID NO 57
<211> Length: 4,427
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 57 558 >HSACMHCP_PEA_1_T13
GTACCAGCACAGCGCCCCTTCAGCAGGCCAGCGCTACTGGCTCCAGATTCCTTTTCCTGTCAGGGTATGGGACTGTG
GAAGCCTGGGAGTGTGCTCAGTGATTCTCTCTTTGCCTCTTCACCCTGCCCTCAGCCCATGGGCATCATGTCCATCC
TGGAGGAGGAGTGCATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAG
TCCAACAATTTCCAGAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCAC
TGTGGACTACAACATCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGA
AGTCCTCCCTCAAGCTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAA
GGAGGCAAGAAAAAGGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAA
CCTGAGGACCACCCATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACC
CCCTGGTCATGCACCAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGC
ATCCTCTACGGGGACTTCCGGCAGAGGTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAG
CAGGAAGGGGACAGAGAAGCTGCTCAGCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGT
TCTTCAAGGCAGGGCTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAG
GCCCAAGCCCGGGGCCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCA
GTGGAACATTCGGGCCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGA
AGAGCGCAGAGACGGAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCC
GAGGCTCGCCGCAAGGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCA
GGCGGAACAAGACAACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCA
AAGTAAAGGAGATGAATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTG
GAAGACGAGTGCTCAGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCA
TGCAACAGAGAACAAGGTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGG
AGAAGAAAGCTCTACAAGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTG
TCCAAGTCTAAGGTCAAGCTGGAGCAGCAGGTGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCAT
GGACCTGGAGCGAGCAAAGCGGAAACTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATG
ATAAACTGCAGCTGGAAGAAAAGCTTAAGAAGAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAG
CAGGCGCTGGCCCTTCAACTACAGAAGAAACTGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGA
GGCCGAGCGCACCGCCAGGGCTAAGGTGGAGAAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGC
GGCTGGAAGAGGCCGGCGGGGCCACGTCCGTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATG
CGGCGGGACCTGGAGGAGGCCACGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGT
GGCCGAGCTGGGCGAGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGC
TGGAGCTGGATGACGTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACG
CTGGAGGACCAGGCCAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCG
AGCCAAGCTGCAGACCGAGAATGGAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCC
GGGGGAAGCTCTCTTATACCCAGCAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCC
CTGGCCCATGCACTGCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAA
GGCCGAGCTGCAGCGCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCA
TTCAGCGGACTGAGGAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAG
GCTGTTAATGCCAAGTGCTCCTCACTGGAGAAGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGA 559
CGTAGAGCGCTCCAATGCTGCTGCTGCAGCCCTGGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGA
AGCAGAAGTATGAGGAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTC AAGCTCAAGAACGCCTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGAGGA AATCTCGGACCTTACTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAGCTGG AGGTGGAGAAGCTGGAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGCCTCCCTGGAGCACGAGGAGGGCAAGATCCTC CGGGCCCAGCTAGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACA GGCCAAGCGCAACCACCAGCGGGTGGTGGACTCGCTGCAGACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGG TCCTGAGGGTGAAGAAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCC GCCGAGGCCCAGAAGCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGGACACCCAGATCCAGCTGGACGATGCGGTCCG TGCCAACGACGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTGGAGGAGC TGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACCAGCGAGCGGGTG CAGCTGCTGCATTCCCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAGTC GGAAGTGGAGGAGGCAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCACGGATGCCGCCATGA TGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAACATGGAGCAGACCATT AAGGACCTGCAGCACCGGCTGGACGAGGCCGAGCAGATCGCCCTCAAGGGAGGCAAGAAGCAGCTGCAGAAGCTGGA AGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGA AGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGACAGAGGAAGACAAAAAGAACCTGCTGCGGCTACAGGACCTG GTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCAAGCCAACACCAACCT GTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCTGAGTCCCAGGTCAACA AGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCACGATGAGGAGTGACACTGCCTCGGGAACCTC ACTCTTGCCAACCTGTAATAAATATGAGTGCCAAACTC
<210> SEQ ID NO 58
<211> Length: 2,533
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 58
>HSACMHCP_PEA_1_T14
GCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCGCCAGGCTAAGGTGGAGAAGCTGCGCTCAGAC
CTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCCGGCGGGGCCACGTCCGTGCAGATCGAGATGAA
CAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCACGCTGCAGCACGAGGCCACTGCCG
CGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCGAGCAGATCGACAACCTGCAGCGGGTGAAGCAG
AAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGACGTCACCTCCAACATGGAGCAGATCATCAAGGC
CAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGCCAATGAGTACCGCGTGAAGCTAGAAGAGGCCC
AACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGACCGAGAATGGAGAGTTGGCCCGGCAGCTAGAG
GAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCTTATACCCAGCAAATGGAGGACCTCAAAAGGCA
GCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACTGCAGTCGGCCCGGCATGACTGCGACCTGCTGC 560 GGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGCGCGTCCTGTCCAAGGCCAACTCGGAGGTGGCC
CAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAGGAGCTCGAAGAGGCCAAAAAGAAGCTGGCCCA
GCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCACTGGAGAAGACCAAGCACCGGC
TACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCAATGCTGCTGCTGCAGCCCTGGACAAGAAGCAG
AGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCTGAGCTGGAGTCCTCACAGAA
GGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGCCTACGAGGAGTCCCTGGAGCACCTAGAGACCT
TCAAGCGGGAGAACAAGAACCTTCAGGAGGAAATCTCGGACCTTACTGAGCAGCTAGGAGAAGGAGGAAAGAATGTG
CATGAGCTGGAGAAGGTCCGCAAACAGCTGGAGGTGGAGAAGCTGGAGCTGCAGTCAGCCCTGGAGGAGGCAGAGGC
CTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTAGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGA
AGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACCACCAGCGGGTGGTGGACTCGCTGCAGACCTCC
CTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAGAAGAAGATGGAAGGAGACCTCAATGAGATGGA
GATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAAGCAAGTCAAGAGCCTCCAGAGCTTGCTGAAGG
ACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGC
AACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGGA
GCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCATCAACCAGAAGAAGA
AGATGGAGTCGGATCTGACCCAGCTCCAGTCGGAAGTGGAGGAGGCAGTGCAGGAGTGCAGAAACGCCGAGGAGAAG
GCCAAGAAGGCCATCACGGATGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGA
GCGCATGAAGAAGAACATGGAGCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCGAGCAGATCGCCCTCA
AGGGAGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAG
CGCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGACAGAGGAAGA
CAAAAAGAACCTGCTGCGGCTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCG
AGGAGGCGGAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAG
CGGGCGGACATCGCTGAGTCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCA
CGATGAGGAGTGACACTGCCTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCAAACTC
<210> SEQ ID NO 59
<211> Length: 2,477
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 59
>HSACMHCP_PEA_1_T17
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG
ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT
CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA 561 AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC
TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC
CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA
AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC
GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG
AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA
ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC
TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA
TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT
ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG
GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA
TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT
TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC
ATCGCTGGCTTCGAGATCTTCGACTTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCA
GTTCTTCAACCACCACATGTTCGTGCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACT
TTGGCATGGACCTGCAGGCCTGCATTGACCTCATCGAGAAGGTGCCTCCTTGGCCTCACCACCTATGCCCCCTCCTC
TGCCATCCAGACAAAGTGGTGGCTGAGTCCCTTCTACACCCAAGAAACTAGAGTCCCAAGAATCCCAGGCCTTTCTC
CAGGCCCAGCTTCTCCCCACTGTGAAGTCATGGGCATGAACAGGATGATCCCCCCACTCTTCCTTTCCCAGGACCTT
GCACTTTATGCCCCTTTGTGGTGGTCCCCTCAGTGTCTTAAGAGTGAGATGTAGTGAAGGAGAGGCCCCTGGCCCCT
CTGACCGCCCATGAGAAGCGTCATTCATGGAAAGATCCTAGGCTGAAATTAGAGATGTTTGGCCTCCCACCACCTTC
CTGTTGGTTGAGAAATAAGCCAGTCTCCAGCCCTCTTGCTTATGGGCATTCCTCAGAAGAGACAAGGCCGCAGGCGG
GAGGCCCCATAGGCCGGGGCTGACTTGCTCTCAGTGAACCTCTGCTCTTTGTCAGCATAGGCCAGAGCCCGGATTGT
CTGACCCACACCCAGCCCAGCCACGGCCTTCATGAAATGGGAGCTTCCCCACATGCTTTGGGTCATTATCCAGATTC
TTAACCAGAGTTCTCATGTTTCAGAGCCCTCAGAATGCCATAAAACTGTGTGTGGAAAAAAGCATGTGTACATTCAT
ACATACATGTGTGTGCTTGTGCATGTGTGTGTGTGTACGTGTGTGTGTGTACATGCGTTTTTCTGGAGAGACAGTCT
TTAGCTTCAACAAATTCTTAAAAGGATTCCTGCCCCAAGAAAAATCAAGAACCACCAGGTTTTTGGAAGTGCAGAGT
GTGGTAAAGAACC
<210> SEQ ID NO 60
<211> Length: 6,903
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 60
>HSACMHCP_PEA_1_T26
GAGGACAGATAGAGAGACTCCTGCGGCCCAGATTCTTCAGGATTCTCCGTGAAGGGATAACCAGGGGAAGCACCAAG
ATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGGAGCGTCTAGAGGC
CCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTCAAAGCCAAGATTT 562
TGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAGACGGTGACTGTGAAGGAGGACCAGGTGTTG
CAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCTGACCTTCCTGCACGAGCCCGCGGTGCTTTT CAACCTCAAGGAGCGCTACGCGGCCTGGATGATATATACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACA AGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGCCTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATC TTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGATCGGGAGAACCAGTCCATCCTCATCACGGGAGAATC CGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTGACCGTGGCA AGAAGGACAATGCCAATGCGAACAAGGGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTC GGCAATGCCAAGACTGTCCGGAACGACAACTCCTCCCGCTTTGGGAAATTCATTAGGATCCACTTTGGGGCCACTGG AAAGCTGGCTTCTGCAGACATAGAGACCTACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAA ACTACCACATCTTCTACCAGATTCTGTCCAACAAGAAGCCGGAGTTGCTGGACATGCTGCTGGTCACCAACAATCCC TACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGATGACTCCGAGGAGCTCATGGCCACCGA TAGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACT ACGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGCCAGACGGCACCGAAGATGCTGACAAGTCG GCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAACGAGTA TGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGTGTATGAGAAGATGT TCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCATAGGAGTCCTGGAC ATCGCTGGCTTCGAGATCTTCGACCCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGCATGTTCCCCAAGGCCAC TGACATGACCTTCAAGGCCAAGCTGTACGACAACCACCTGGGCAAGTCCAACAATTTCCAGAAGCCACGCAACATCA AGGGGAAGCAGGAAGCCCACTTCTCCCTGATCCACTACGCCGGCACTGTGGACTACAACATCCTGGGCTGGCTGGAA AAAAACAAGGATCCTCTCAACGAGACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAGCTCATGGCCACTCTCTT CTCCTCCTACGCAACTGCCGATACTGGGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAAGGGCTCATCCTTCCAGA CGGTGTCGGCTCTCCACCGGGAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCCATCCTCACTTTGTGCGT TGCATCATCCCCAATGAGCGGAAGGCTCCAGGGGTGATGGACAACCCCCTGGTCATGCACCAGCTGCGCTGCAATGG CGTGCTGGAGGGCATCCGCATCTGCAGGAAGGGCTTCCCCAACCGCATCCTCTACGGGGACTTCCGGCAGAGGTATC GCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAGAGAAGCTGCTCAGCTCT CTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGTTCTTCAAGGCAGGGCTGCTTGGGCTGCTGGA GGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCATGCAGGCCCAAGCCCGGGGCCAGCTCATGCGCATTG AGTTCAAGAAGATAGTGGAACGCAGGGATGCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATGGGGGTCAAG AATTGGCCCTGGATGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACGGAGAAGGAGATGGCCAC CATGAAGGAAGAGTTCGGGCGCATCAAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAAGGAGCTGGAGGAGAAGA TGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAGACAACCTCAATGATGCTGAG GAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGTAAAGGAGATGAATGAGAGGCTGGAGGA TGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAGACGAGTGCTCAGAGCTCAAGAAGGACA TTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCAACAGAGAACAAGGTGAAGAACCTAACA GAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTACAAGAGGCCCATCAGCA GGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGTCAAGCTGGAGCAGCAGG TGGATGATCTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAGCAAAGCGGAAACTGGAG GGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTGGAAGAAAAGCTTAAGAA 563
GAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCTTCAACTACAGAAGAAAC
TGAAGGAAAACCAGGCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCGCCAGGGCTAAGGTGGAG AAGCTGCGCTCAGACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCCGGCGGGGCCACGTCCGT GCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCACGCTGCAGC ACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCGAGCAGATCGACAACCTG CAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGACGTCACCTCCAACATGGA GCAGATCATCAAGGCCAAGGCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGCCAATGAGTACCGCGTGA AGCTAGAAGAGGCCCAACGCTCCCTCAATGATTTCACCACCCAGCGAGCCAAGCTGCAGACCGAGAATGGAGAGTTG GCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCTTATACCCAGCAAATGGA GGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAGGCGAAGAACGCCCTGGCCCATGCACTGCAGTCGGCCCGGCATG ACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAGGCCGAGCTGCAGCGCGTCCTGTCCAAGGCC AACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCATTCAGCGGACTGAGGAGCTCGAAGAGGCCAA AAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCACTGGAGA AGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCAATGCTGCTGCTGCAGCC CTGGACAAGAAGCAGAGAAACTTTGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCTGAGCT GGAGTCCTCACAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAGCTCAAGAACGCCTACGAGGAGTCCCTGG AGCACCTAGAGACCTTCAAGCGGGAGAACAAGAACCTTCAGGAGGAAATCTCGGACCTTACTGAGCAGCTAGGAGAA GGAGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAGCTGGAGGTGGAGAAGCTGGAGCTGCAGTCAGCCCT GGAGGAGGCAGAGGCCTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTAGAGTTCAACCAGATCAAGG CAGAGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACCACCAGCGGGTGGTGGAC TCGCTGCAGACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAGAAGAAGATGGAAGGAGA CCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAAGCAAGTCAAGAGCCTCC AGAGCTTGCTGAAGGACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCC ATCGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTGGAGCAGACAGAGCGGTC CCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCA TCAACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAGTCGGAAGTGGAGGAGGCAGTGCAGGAGTGCAGA AACGCCGAGGAGAAGGCCAAGAAGGCCATCACGGATGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACAC CAGCGCCCACCTGGAGCGCATGAAGAAGAACATGGAGCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCG AGCAGATCGCCCTCAAGGGAGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTG GAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTA CCAGGTGCGGCGGACGCCAGACACCGGGAGTAGATGTGGAAGTTTCTTCTCTGGCCCCACTGCCCCGCCCTCACAGG GCTCCTCTCACCTCCTCCTTGAGATGCTGTTGGTAGATTTAACGTTCTTCTCACGCTCTGCAGTCAGTTTGACTTGA GTCTATGAGTTTTTCCAGCAAATGAAGAATCTACTTCTACTTCCTGAAAACTCTTCTAACTAGTCTTTCCCCAGGTT TCTTTCTTTCTTTTTTTTTTTTTTTAATAACTCTAAGTGCTACCATGAAGACTTCAGAACAGTTCAAAGAATCCTTC CACCTTCGACTGTGGGGATAAGAGTCAGGGGAGGGGAAAAGACCCGGAAATCTTCCATAGAACTTCTGGCACACAAA GAGAAGGCCACAGAGAAAGAGGACCCTAGAATGCTCTAAAACCTCCACTTGCATAGCTGAGAGCTGTGCCCTTGGCC CGTTATTTTCAGTGTACCTGGGAAGAAAAGGCCAAGGAGACGAGGGTGTCAGTCCATTTGATAGATGGATACCAGAG GCACAAGAAAGAGGTTACAGATACAGAACCACAGAGTGATTTGTGGACAGAAGTAGAAATGGCATCCTGGCACATAC 564 AATGATAAAGAGATAGGAATGATCGAGTGACGTTGGAGCCAGTGATCCCGATGCCTGAATTCTGGCCCAGTACAATA
TATTAGAATGTAGAATAATCTGGATTATGATAATACCCCCTTCTTTCTGCATTCTTTTTCTGGTCAAGAACTACTGG
CCAAGAGAACCTATGTAAGTCCAGGTTGGAGCTTTATCCACCATACTGGAGCTGGAACAGACCTGGTGCTTTTATAT
TACCACATTAGGGAATTCCATTAGGTTCTGAGCCCCTCCCCCTACTTCTAGCTTTATGACTTCAGCCTTCATTGCTC
TGTGGATCCCTGACTGACAACCTTGCATTGCCCCTTTGACCTACGATAGAGTCAGAGAATCTTCCCCACCACCTCTT
TGACCTGGATCATTGCAGGGAGGGGCAGCAAAGGCAAGGGGAGAAGAGTAAAATGATGGAGGAGGGAAAGGTGATTG
CATTTGCTCCCCCTCCAAACCAGCTTCTCCCACCCTCCCACCCCCAGACAGAGGAAGACAAAAAGAACCTGCTGCGG
CTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCAAGC
CAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCTGAGT
CCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAGCAAAAAATGCACGATGAGGAGTGACACTGC
CTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCAAACTC
<210> SEQ ID NO 61
<211> Length: 22
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 61 >S67314 segllF TCCCCTGAGAGCTGTAGAAGCT
<210> SEQ ID NO 62
<211> Length: 19
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 62>S67314 segllR
CGGCCTGTGTGAGTCCAAA<210> SEQ ID NO 63
<211> Length: 101
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 63>S67314 segll
TCCCCTGAGAGCTGTAGAAGCTGGGACAAGAGAGTGGTTGTGGGTCAGGGTGGTATCAGGTGGGAATTTTCTGTGTA GTGGCTTTGGACTCACACAGGCCG<210> SEQ ID NO 64 <211> Length: 20 <212> Type: DNA 565
<213> ORGANISM: Homo sapiens
<400> sequence: 64>S67314 segl5F Forward primer TTCCTTGGCATCTCCAATGG
<210> SEQ ID NO 65
<211> Length: 997
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 65
>S67314_PEA_l_node_0
TCTGCAGGAGGGGAGCTGGGAACGACCTGAGCTAAAGCTCGGAGCTGTGCGAAGAAACCGGAAAAGCCCAGAGCACT
TGCAGGGGCGGGTGGGGAGCTAGATGGTGGGGTGGGGTGGGGACGGAGGAGGGCCAGCAGGAGACATTCCGCAGGGA
GGGGCAAGCACGTGTGAGGCGGGCGGGGCGCGAAGGGTCAGGCTTTTGCTCAAAACAGGCAGAGGACAAGGTCAGCT
CAGCCGCAGACCGAGCCGCTGGTGACTGTCTCCGCCACCAGGCAGTGAGAGTGAAGGGAGAGCGCGAGCTCTGAAGC
CCGCTAGACTAAGCTTGCAATCTGAGCTCCATTCACCCCCTCCTATTTCTTGAGACCTTGTCAGTTCCCCTGTGAGC
CTCGGACTCCTCACTTGTAAAACGAGGACAGATGCCCGTGCCAGAAGTCAACCAGAGCTTTCCCCGGCGTGGGCACC
AGCCCAAGGGCGTTTTGCTTTTCTAGTCTCATCTCTGCTCTGACGCTAAGCTCAAAGAGGGACTGGGGGACGGGAAG
ATATCCACCATGGCATGCGCCCTAGCTCTCGGGCTGGTGTTGGCTGCTTCCTTCTCAGATTCCAGAGTGCCTAGAGG
CCAGGAAAGGGAGAAGGTCCTACCAGCCTGGGGTAGGGACTCGGGGGCCAGGCACTGGCGCTGACGCAGGCTAGCAG
GGCGCCACTGGCTGGTCCCCACCCACCTCGGTGGGTTGGGGGATGGGCGCACCAGCCCCTCCTGGGTGAGCCCTAGC
CTGGGGCTTCCTATTTCGGGAGCCGGGGGCGTGGGCCACGTCTCCTCATGTGATGCGAGGGCTATTTAAAGCGGCAG
CCCGGGCAGGGAGCCGCCGTCGGAGCCCTTGCACGCCTGCTCTCTTGTAGCTTCTCTCAGCCTAGCCCAGCATCACT
ATGGTGGACGCTTTCCTGGGCACCTGGAAGCTAGTGGACAGCAAGAATTTCGATGACTACATGAAGTCACTCG
<210> SEQ ID NO 66
<211> Length: 838
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 66
>S6731 _PEA_l_node_ll
GTAAGATGGGCAACTTTGGAGCTATATCTGATTGGTTATTACTACTGCTCTTTCAGCCAAGCCTGTTCTAAAAAGCC
AAGTCCTCCCCTGAGAGCTGTAGAAGCTGGGACAAGAGAGTGGTTGTGGGTCAGGGTGGTATCAGGTGGGAATTTTC
TGTGTAGTGGCTTTGGACTCACACAGGCCGGAACTCAAATCTTACCTTATAGGCTACATGACTGTGGGCAAATCACC 566 TTTTCCAAGTGCAACTGTAAAACGGGTATTAATAATACCAACCTTGTAGGGCTGCTGGGAAGCCTGTAAGAGACAGT
GTATGCACAGCACAAAGCATCACTGATTGAGGAACACAGCAGGTGCTCCATGTCCTTTGTTTGCTCTTCCTGTGTTT
CTACCTTGCCTCACCTCAGGAAGAAGTAGAAAACAGGGCCAAATCTGATCCCAGGCCCTCTAGGAGGGGCTCCCATT
GCCTATCTCAGCATTCCCTTTCCTCTCCTCCCTAGGACTGCATTGTCACTTGCAGGGACAGGCTCGTGACTGGTGGG
GACACTGAATGACAGTACAGTCCTTTCTTCCCCATTCTAGTCCTACCCCATTTTCATGCTTTCTATGTCTGGCCTAC
TGAAACTACTTGACTACTGCTTGGGTAGGAAGTACCACAGCCAGGCTGGCAGATCTGTTCAAGCTTGGGGACTTCAC
TTGGAGAATCTAGCCTTGACTGAATTCCCCCCAGACCCAGGGAGAGCAGCCAACTGTGGATTCTGCCTAACCACAGG
GCCTCAGGTTTTCACCTAGGCATCTTCACTGCACACCTTCTTGGGTCAGCATAACCTGTTAACTGCAT
<210> SEQ ID NO 67
<211> Length: 2,226
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 67
>S67314_PEA_l_node_13
ACACTCACCCACGGCACTGCAGTTTGCACTCGCACTTATGAGAAAGAGGCATGACCTGACTGCACTGTTGCTGACTA
CTACTCTGCCAATCGGCTACCCCTCGACTCAGCACCACATTGCCTCATTTCTTCCTCTGCATTTTGTACAAATCCAC
GAATTCTTCTGGGGTCAGGTGCCACTGACCGGGATCCAGTTCCAGTTCCCATGGTGTATGTGGTTTTTTTTTTTTTT
TTTTAACTGCACTCATAGGGTGCTCTGAGGTCAATAAAGCAGAGCCAAGGCCACCCAGTTGCCTTTTTGCCTTTGGT
AACATAACTCTGGGAGTCTTGGTTTATCCTGTGTGTCAGAGAGTGGGCAGAAATAACGGCCTGAAGGTTACTGAGGA
AGAAGCACTGGATGGGAGACTGAAATGGACAGTCTCGGAGCCTGTTAATCAGCTGATCACCTTACACATTTAATAAT
AAAAGAGCTGTACCTACACGTTGCCTTTACACTGCCCCCCCTCCATGGTCAAATGACCTAGTTCAGTCAGTGATGGG
GCTTCCCCAGGTTTGGCTATTGAACTGTCACTTCAGGCCCATCCTACACTGAAAGCTCTTGGGTCTGGCTGTTCTCT
GTGAAATGCTGTAGTCTCTCCCTTTCCAGAATTCAGGTTCAGGGCACAGAACCCAGGCTTGTACCATGGTGGTGGGA
GAAAATGACCACTGGCCAAGAGGACTGCTGACCTGTGCACCAGGCTAGTACTTATGACTACAAATTCTTACTGCTTC
TCTAATCAACTCTGAGGGAAGAGGGCATCTGATCATTACAAAAGGGAGGGCTTATAAGTGATCTCCCAAGAAGGCAG
TGATCTGCTAGTGCCTTTGGCTCTGTACCTCTGCTGGGCATCTCTCCAAGGTCTAAGGTAACATATTAAATGTTTTT
GTCAGCTAATGCAGGCTCAGTGACTTTAAGTCTGTAAGTTACCCAGGAAGAAGGATTATAGGAAAAATAACTCAGTA
AGTTTAAAACCAAACACATTTCCATTTAGTGACAGGAATTTAAGCAAGGACCTGAAGTAGAATCAACTGATTCACAC
AGTAGTAAATACAAAGTAGAACAATGATCTTGGCTTCGCTGTCTGGTTCAGTGGTCTGCTGGAATGCAATACACAAG
TTAAGTCACACTGCAGACTGTTTTCTAGCTGTGGCCGCTGGATGCCACTTCTAGCATAGTAGAACTATGTTAGGAGG
AATGGGAAAAGTGAGCACCACTTCTCACCATGTTCCCCCCTCCTGCTGCCAGTCTCTGCTCCCATGTTGGATGCAGC
AGAGATCACCCACCAGTTGGCCCAGGACAGACCAATAGGAAGGGTCCAATCACTCTAACTACAGCCGAACTCACCTC
CACAACAGTCTCTGTGGCTCTAGCCTGGACTCCTTTACAGGAATCCAGCTCTGGCAGTGGCAGCTGGAGAGGGTAAT
AGGGCCTCCTGCTGAATGAAGGAAGTTGGGTGAATGAATGGGTGAGCTGCAGGGTTCACTTGCAAAGGGACCAGGAG
TGATAAGGAAACAACAACTCATTCAGGCAGCTGCTTTTGACCTCTAACTCCCAAACCTGCCTGTTGCATGAGGGGAA
GCCATCTCCCATGGGAGCGAAGTTAATGGGGTGGGAGGCTATATTCTCACTATTGAGTCTTTCCAGGAGTCTCAAGG 567 CACAAGGCTCCTGGTTTCTTACTCTCAACCACCCCCTACACTCTTTATACTCTCACTCCTTGTGCTTCTTCTTGTGC
TTCTTCTTCTTTTTCTTCTTCTTTGCTGCCTTGCTGTCTTTTGATGTGTGCCTTGCCCTCTTGCCTGTATCACTCTC
AGAGTCTGAGCTGTCAGAGTCAGATGACTTCCTATCTCTATGTTTCTTTTTCTTCTTCTCCTGAAAAGAAAATTTTA
AAAATCAACACTGTATGTGTATATTTGCTTTTAACAATCATAGCACATAATTGGCCAGGTGCAGTGGCTCACACCTG
TAATCCTAGTACTTTGGGAAGCCGAGGTGGGAGGAATGCTTGAGGCCAGGAGTTCAAGATCAACCTGGCTAACATAG
CAAGATCTCATCTCTAAAAAGAGAAAAAAAGAAAAATTATAGCACACAATCAATAGGGGACCACTTAATTTTCTTTT
AGACAGTCTCGCTCTGTTGCCCAGGCTAGAGTGCAGTGCAGTGGCACGATCACAGCTCACTGCAACCTCA
<210> SEQ ID NO 68
<211> Length: 461
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 68
>S67314_PEA_l_node_15
GATGTTCTGACAGCCTGGCCAAGCATCTACAGGAGACAAGTCAAAGTTTTAAGAGAAGATGAAATAACAATTCTTCC
TTGGCATCTCCAATGGAGTAGAGAGAAGGCAACAAAGCTTCTCAGACCCACATTACCGAGCTATAACAACCATGGCT
GGGAGGAGCTGAGAGTTGGCAAATCAATAGTTTAGCTATGTTGCTGAACCTTCCTGGATGGCAAGACCATGGAAGTC
CATCACAAGATATTATGGGGTCAGGAGCCTCACTGGGTTCTGCCCCTTATATAGGTGAATATCCTGGGAAAGTAAAA
ATGAAAATACAGAGTCTGGCACCAGTTCCCTGCAAGCCTGGTCCAGCCTGGATAAAGAAGTGAGGAGAGTAATAATA
CTGCCTTACACCTAAACAGTGCTTTAGTTTATCAAGCTTTTTGCATCCTTATCTTACAATAATAGTCTGTAGAGTC
<210> SEQ ID NO 69
<211> Length: 550
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 69
>S67314_PEA_l_node_17
ATGGAAAAACTGCAACTCAGAAATGTAAAGTGAGTCGACCAAGGCTAAAGCGGCAAAACCACTATACTTTATAACAC
AGAGTTTGGCACTATTTCCACTTTGTTCTCTCTCAAAGATGAAGGCTCAGGAGGAGGGAAGATAAAAACAAATCACT
GGAGAGTCCTGGCATGCTGGAACATGGACTCTAGCTAGCAAGAAGGGCTCAAGGAGGTGGCCTTCTCCTAGACCTCA
ACTTTGATGCAAAAGCTGTTTTGCAGCCTGAACAAAGACAATCCAATCCTCCAGCAAATGGCGTCATTTTCCCTACG
TGTCTAGCCTTGAGCTACAGAACAAAAGAACAATCACATCCGAAGTTGTAGTTCGCCTGGTTGCGGTGGCTCACGCC
TGTGATCCCAGCACTTTGGGAGGCCAAGGTGGGTGGATCACCTGAGGTCAGGAGGTCGAGACTAGCCTGACCAACAT
GAAGAAACCCCATCTCTACTAAAAATACAAAATTAGCTGGGCGTGGTGGCACATGCCTGTAATCCCAGCTACTCGGG
AGGCTGAGGCA 568 <210> SEQ ID NO 70
<211> Length: 173
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 70
>S67314_PEA_l_node_4
GTGTGGGTTTTGCTACCAGGCAGGTGGCCAGCATGACCAAGCCTACCACAATCATCGAAAAGAATGGGGACATTCTC
ACCCTAAAAACACACAGCACCTTCAAGAACACAGAGATCAGCTTTAAGTTGGGGGTGGAGTTCGATGAGACAACAGC
AGATGACAGGAAGGTCAAG
<210> SEQ ID NO 71
<211> Length: 102
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 71 >S67314_PEA_l_node_10
TCCATTGTGACACTGGATGGAGGGAAACTTGTTCACCTGCAGAAATGGGACGGGCAAGAGACCACACTTGTGCGGGA GCTAATTGATGGAAAACTCATCCTG
<210> SEQ ID NO 72
<211> Length: 33
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 72 >S67314_PEA_l_node_3 CTCATATACTCATAACCTTCCCCCTACCCTCAG
<210> SEQ ID NO 73
<211> Length: 237
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 73
>N56180_node_2
ATGCGTGCGTGCGTGCGTGCGTGTGTGTGTGTGTGTGCCTCTGCTCTTTGTCCTGAGCCCACGATTCCAGAGCTGGC 569
TGGACCCAAGGAGGTGAAGAGTCACTTTTCAGCCCCAGGAAGGGCAAAGAAGAGAGAAAATCAGCCTGTCTGCTCTC
TCCTTGGCTCAACAAGGCCTCTAACAGTCTTCTGTCCTCTATTCTGCACACGGCATATTTGGGAACGAGAAACAAAA GTTTTC
<210> SEQ ID NO 74
<211> Length: 131
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 74
>N56180_node__20
GTTGCAAAGAAATTATCTTTGAAGATGAATGAGGTTGACTTCTATGAGCCATTTATGGATGAGCCCATTGCCATCCC
CAACAAACCTTACACAGAAGAGGAGCTGGTGGAGTTTGTGAAGGAACACCAAAG
<210> SEQ ID NO 75
<211> Length: 281
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 75
>N56180_node_22
ATCAAGGAATTGGACTCAATAGTTAAGTAACTTAGCCAAGGATGAACACTCTATGCATAGAACTTCTGGGAGAGAAA
TGCTTGATACCACTTAGTGTAGCTCCAGCATGGATCAGCAAACTTTTTCTGTAAAGAACAAAATGGTAAATATTTCA
GGTTCTGTGGGCCAGATGGCGTCTGTAGCAACTACTTGACTGCGGCTGTGGCATGAAAGCAGCCATGGATCATGTAT
AAACAAATGGGTGTGGCTGTGTACCAGTAAAAGTTTATCCGGAAAAAAAG
<210> SEQ ID NO 76 <211> Length: 136 <212> Type: DNA <213> ORGANISM: Homo sapiens
<400> sequence: 76
>N56180_node_28
TCTATAGAATAATCCTATAATTGAGGGTGAGCACCAAATGTCCTAAGAAGTCCTCGTGGAAAAATCACACTCTGCTC
TCCACATTAGAAGCTGTGTATGTGCAGGGGTTACTCAACTCTCTTGAATCCTGTTTCAG
<210> SEQ ID NO 77 <211> Length: 248 <212> Type: DNA 570 <213> ORGANISM: Homo sapiens
<400> sequence: 77
>N56180_node_34
CTGCTGAGGAGCTGGAGGACTGGATTGAGGATGTGCTTTCTGGAAAGATAAACACTGAAGATGATGATGAAGATGAT
GATGATGATGATAATTCTGATGAAGAGGATAATGATGACAGTGATGACGATGATGATGAATAGCCCAACTCCAAACA
ATTCTGATGAAAACAAAATCACAGCACCCACTACCATACAGACAGCACAAGGTGGCAGCAAGCAATTCTGCCCCACA
CCCAGCCAGCTCCTTTC
<210> SEQ ID NO 78
<211> Length: 1,124
<212> Type: DNA <213> ORGANISM: Homo sapiens
<400> sequence: 78
>N56180_node_36
CATCTCTTTTCCCACTCCCTTTGCGTCAGGAGCAGCATCATTCAGCAAATGCCTTTTCAAATGCAGCAATCCCACTT
AGCAGGGACAGGAGAAAAATTATTCCCATGTTGACTGTCTTGACTGTCACGGAACAGATCTTGTTCTTTGCTGGACC
ATCAAGGGTCATGGCAGTGCCTGAACATGGCAGTCTAGGGTGAACAATCCCCTAACACAAGTTTACTTGTCTTTGAT
TATGACAGTAACAAAATTGACAGCTTTCTAACTCACAGGCATAGAGTGACCTTTTAATCAGAGCCCAGGGAAGACAC
ATGATTAATGATTTAGCTCCCTCCATACCTCGAACATCAGTTGGGATCCCTCCTCCAGCCAAGATGATCCTTCTTAG
AGAAGGCTCAGCCTTGGAAGCAAACTTATAAATCATATTCTCATGGCTTTGTTAAACTTATTTCAAGTGATGGTCAT
TCATATCACTATGAACTTGGATATTCAAGCCTTTGGATGGCTATGGAGAGGCCTTGAAATGTGTACAGGTGTCACCA
TCATTTCTAGTATATTAGGAAACTGGGATGGGAGGTTGATTTGCTCTCTAAACTTCCCTCTAGTTGGCAAGTCTCAC
ATATTCATCAGCAGGAGTGGAGGGTGGGGGAAAACTAGAAAGATGAAAACTTTTACATTTTTCTGATGGGTTCATGT
CTCTGATTGGGTCAGCTGGCTTCCTAGCCTAAGCTGGGATCTGAATACCCCTTCTCTGTAGCTGCTAGTGAGCCTTC
CCATTTAGATTAAAGATTGCTTTATCCAGCAGTCAATTAACTCTCCAGTTATCAGTACTCCCACAATTGGCCAGGGC
AACAATAATTGGAGTTCATACTGATGCCCTGAGGCACTGAAAAAAAAAAAAATCCCAAAGTGCCTTCTGAGCTGTCT
AAAAGTTACATTGTGCTTGGTAGATTTAGTGTTAAGTGTGCAGTATAATTTTCTAATTTATTTTCTCAATCTTTTAG
CACATGTGTAAGACACTGTGCAAATTTTTTGAAAATAGAGCAATACTTTTTGTGGAATACTAGCTAACTAATTCTGT
CATTAAACTCATATTTTGAAAATATTCAGACAATGTTGAAAATCCT
<210> SEQ ID NO 79
<211> Length: 181
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 79
>N56180_node_4
GGCAGAAGAGGGGCTTAATTTCCCCACATATGATGGGAAGGACCGAGTGGTAAGTCTTTCCGAGAAGAACTTCAAGC 571 AGGTTTTAAAGAAATATGACTTGCTTTGCCTCTACTACCATGAGCCGGTGTCTTCAGATAAGGTCACGCAAAAACAG
TTCCAACTGAAAGAAATCGTGCTTGAG
<210> SEQ ID NO 80
<211> Length: 141
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 80
>N56180_node_6
CACTGGCAAATATCCCAGTGGTGGTTGCATTTCCAAACCCCAAGAGAGGAAGGCAAAATGAAGTTGCTGGAGTTGAG
TGAATCTGCAGATGGAGCTGCGTGGAAACGCTGGGGAGGGAATAGCAACACACACAGGATTCAG
<210> SEQ ID NO 81
<211> Length: 33
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 81
>N56180_node_0
TAATGAGACAGAGGCTGAGCAGAGCTATGTAAG
<210> SEQ ID NO 82
<211> Length: 100
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 82
>N56180_node_10
GTTTTGATGAAGAAGGAAGCCTGTATATTCTTAAGGGTGATCGCACAATAGAGTTTGATGGCGAGTTTGCAGCTGAT
GTCTTGGTGGAGTTCCTCTTGGAT
<210> SEQ ID NO 83
<211> Length: 112
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 572 >N56180_node_12
CTAATTGAAGACCCAGTGGAGATCATCAGCAGCAAACTGGAAGTCCAAGCCTTCGAACGCATTGAAGACTACATCAA
ACTCATTGGCTTTTTCAAGAGTGAGGACTCAGAAT
<210> SEQ ID NO 84
<211> Length: 74
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 84
>N56180_node_14
ACTACAAGGCTTTTGAAGAAGCAGCTGAACACTTCCAGCCTTACATCAAATTCTTTGCCACCTTTGACAAAGGG
<210> SEQ ID NO 85
<211> Length: 95
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 85
>N56180_node_16
GTGCTGTGGCTCACACCTGTAATCCCAACACTTTGGGAGGCTGACGGGGGTGGATTGCATGAGCCTTGGAGTTGGAG
ACCAGCCTGGGCAACATG
<210> SEQ ID NO 86
<211> Length: 115
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 86
>N56180_node_18
TGCAGGCAAACAGCAACCATTCTGCCTTGACAACACACTGAACATGTGGCTGCTTTAATCCAGAGAGAAAATGTCTT
CCTGGCTATCGGCTGGCTCTCCGAGCTCTTTATCTGTT
<210> SEQ ID NO 87
<211> Length: 46
<212> Type: DNA
<213> ORGANISM: Homo sapiens 573 <400> sequence: 87
>N56180_node_24
ACCCACTCTACGTCGCCTGCGCCCAGAAGAAATGTTTGAAACATGG
<210> SEQ ID NO 88
<211> Length: 55
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 88
>N56180_node_26
GAAGATGATTTGAATGGGATCCACATTGTGGCCTTTGCAGAGAAGAGTGATCCAG
<210> SEQ ID NO 89
<211> Length: 101
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 89
>N56180_node_29
ATGGCTACGAATTCCTGGAGATCCTGAAACAGGTTGCCCGGGACAATACTGACAACCCCGATCTGAGCATCCTGTGG
ATCGACCCGGACGACTTTCCTCTG
<210> SEQ ID NO 90
<211> Length: 57
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 90
>N56180_node_3
CCAAATGAAGAGAACTCACTTGTTTATTGTGGGGATTTATTTTCTGTCCTCTTGCAG
<210> SEQ ID NO 91
<211> Length: 75
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 91 574 >N56180_node_31
CTCGTTGCCTACTGGGAGAAGACTTTCAAGATTGACCTATTCAGGCCACAGATTGGGGTGGTGAATGTCACAGAT
<210> SEQ ID NO 92
<211> Length: 46
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 92
>N56180_node_33
GCTGACAGTGTCTGGATGGAGATTCCAGATGATGACGATCTTCCAA
<210> SEQ ID NO 93
<211> Length: 10
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 93
>N56180_node_35
CCTTTTCCAT
<210> SEQ ID NO 94
<211> Length: 84
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 94
>N56180_node_8
CTTGTGGCCCAGGTCCTTGAACATAAAGCTATAGGCTTTGTGATGGTGGATGCCAAGAAAGAAGCCAAGCTTGCCAA
GAAACTGG
<210> SEQ ID NO 95
<211> Length: 214
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 95 >T10377 node 0 575 GGGGGGGCCTTCGCGGTGCAGCTGAGGCTGCAAGTAGCCGGCGCCGTCCCGCGTCGCCCCCGCGCAGGGCGGGCCCC
GCACGCTTATCCTGCCCGGGAGGAACGCCGGCGTCCAGCCCGCTACCGACCGCCGCTGCGGGATGCTGCGCTCCACG
TCCACGGTCACCCTGCTCTCGGGCGGCGCCGCCAGGACGCCCGGGGCGCCCAGCAGGAGG
<210> SEQ ID NO 96
<211> Length: 133
<212> Type: DNA
<213 > ORGANISM: Homo sapiens
<400> sequence: 96
>T10377_node_17
TTTGGAAAACAGCAACATTAAGGATCAAATCAGAAATCTGCAGCAGACGTATGAAGCATCCATGGACAAGCTGAGGG
AAAAGCAGAGGCAGTTGGAGGTAGCGCAAGTTGAAAACCAGCTGCTAAAAATGAAG
<210> SEQ ID NO 97
<211> Length: 126
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 97
>T10377_node_19
GTGGAATCGTCCCAAGAAGCCAATGCTGAGGTGATGCGAGAGATGACCAAGAAGCTGTACAGCCAGTATGAGGAGAA
GCTGCAGGAAGAACAGAGGAAGCACAGTGCTGAGAAGGAGGCTCTTTTG
<210> SEQ ID NO 98
<211> Length: 129
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 98
>T10377_node_21
GAAGAAACCAATAGTTTTCTGAAAGCGATTGAAGAAGCCAATAAAAAGATGCAAGCAGCAGAGATCAGCCTAGAGGA
GAAAGACCAGAGGATCGGGGAGCTGGACAGGCTGATTGAGCGCATGGAAAAG
<210> SEQ ID NO 99
<211> Length: 160
<212> Type: DNA
<213> ORGANISM: Homo sapiens 576
<400> sequence: 99
>T10377_node_27
ATCATGTCGCACGAGCTCTTCTCCAGATTTAGTCTCCGGCTCTTTGGAAGATGATAAGTTGGTAGCCTGCTCTGGGT TGGAAGCGATTCCTTTATTGTTCGTGATTAGAAGAACACTTGTACACTCTCTGCTGGGAAGAGGTGGTATTTATCTA TGATGA
<210> SEQ ID NO 100
<211> Length: 969
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 100
>T10377_node_33
CCAAACAGGCAGGACTCGTGAAATTGTGATGCCTTCTAGGAACTACACCCCATACACAAGAGTCCTGGAGTTAACCA
TGAAGAAAACTCTGACTTAGGCACTCAGAGGCATACACTTTTTACAGATGGACAAAAGCTCTGGAACCCTGTGGCTT
CAAATCCTTTGGGAAGGGTGACTGTTGTTTCCCCTACACACAGTGTAAGCCGGAATGGGAATCGCTGAGGCTCTGAT
CCACTTCTAAGACAGGAAGGAAAGTGAAGGCAGAGTGAGCAGGTAAGAGAGGGATATACAAGGTCACATTTCAGACA
CCCACTCGGCATACCCTGCCGTACTGCATCATCATTTGTTTTCTTTGTAGACACTGAAATCCTATCAGGAGGATTCC
TTCACAATGTATTTTATTTGCTAGACTTTGGTTGGGAGGGAAAAGGACATTAATTTGAAGTTTCATGTTATTCATGC
CAGGATTGTTTGATAGAGCATGAAGGTTTTGTTTACCCATAAAAGTATTAGAGGCAGCGTTTCTCTGATACAGAGAG
GCCTGTCCACAAGAAGCATGGGCACCCAGCCAAACTTGAACCTGGAAGGGAGGGTTCCCGGCCTGCAGGTGCTCTTT
CCTCTTGGTCCCAAGCATCTGTGCAGGGTCGTGGGAGCCACACTGAGAGACTTGTGTGGGCCAGACAAGCTTCATTC
TGATGCGCTAGTCCCTTGGTTTAATTTGTGCCTTATGCTTTCATTGGACCAGCTGAAATCACTGTATTTATTCAACT
TGTGATTTTTTTTTCTTTCTCACTTTAACTTAAAGAGAATTTTATATGTCTTGGAAATTTAATAATTTAGTGTTCTC
AGTATCAATTGGTGTTTTTGTTAAACGAATGAATCATCTGTTCATGCATGCTCTACTTTGATATTATAACCTATGTC
ACATGTGTTTAATAAATACCATATATTTTGTTCTACTAAAAAAAT
<210> SEQ ID NO 101
<211> Length: 93
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 101
>T10377_node_12
GTGAGAGCCACTTTGGAAAAGGTGAGAAAGCGAATGTATGGAGACTATGATGAGATGAGACAGAAGATTCGACAGCT
CACCCAGGAACTATCA 577 <210> SEQ ID NO 102
<211> Length: 114
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 102
>T10377_node_14
GTTTCCCATGCTCAGCAGGAGTATCTGGAGAATCACATCCAAACCCAGTCGTCTGCCCTGGATCGTTTTAATGCCAT
GAACTCAGCCTTGGCATCAGATTCCATTGGCCTGCAG
<210> SEQ ID NO 103
<211> Length: 20
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 103
>T10377_node_16
AAAACCCTCGTGGATGTGAC
<210> SEQ ID NO 104
<211> Length: 110
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 104
>T10377_node_2
TAGCAGTGGTGTTCAGGGTAGGATGCAGTTCTTCGCATTGTGCATAACACAAGCCCTGAACCAGCTGCTTTGGGAAC
CCCTGGGAATAAAGTGCCCTACCTGCCTTTCAG
<210> SEQ ID NO 105
<211> Length: 80
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 105
>T10377_node_23
GAACGTCATCAACTGCAACTTCAACTCCTAGAACATGAAACAGAAATGTCTGGGGAGTTAACTGATTCTGACAAGGA
AAG 578
<210> SEQ ID NO 106
<211> Length: 105
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 106
>T10377_node_25
GTATCAGCAGTTGGAGGAGGCATCAGCCAGCCTCCGTGAGCGGATCAGACACCTAGATGACATGGTGCATTGCCAGC
AGAAGAAAGTCAAGCAGATGGTCGAGGAG
<210> SEQ ID NO 107
<211> Length: 84
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 107
>T10377_node_29
ATTGAATCATTAAAGAAAAAGTTGCAACAGAAACAGCTCTTAATACTGCAGCTTTTAGAAAAGATATCTTTCTTAGA
AGGAGAG
<210> SEQ ID NO 108
<211> Length: 85
<212> Type: DNA
<213> ORGANISM: Homo sapiens
400> sequence: 108
>T10377_node_3
GCACTGCCAAGCCTGGGGCATCTCTGGAGATTGTGTATCCGAGTTTCAGGAGACCATGGAGATCAGCCTCGTAAAAT
GCTCGGAG
<210> SEQ ID NO 109
<211> Length: 101
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 109 >T10377 node 31 579 AATAATGAACTACAAAGCAGGTTGGACTATTTAACAGAAACCCAGGCCAAGACCGAAGTGGAAACCAGAGAGATAGG
AGTGGGCTGTGATCTTCTACCCAG
<210> SEQ ID NO 110
<211> Length: 87
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 110
>T10377_node_5
GCAAATGTTTGCAGACTACGGCTGACCGTACCTCCTGAGAGTCCAGTTCCTGAGCAATGTGAAAAGAAGATTGAGAG
AAAAGAGCAG
<210> SEQ ID NO 111
<211> Length: 106
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 111
>T10377_node_8
CTTCTTGACCTGAGCAATGGAGAACCTACCAGGAAACTTCCTCAGGGTGTTGTTTATGGTGTGGTGCGAAGATCAGA
TCAAAATCAGCAGAAAGAAATGGTGGTGT
<210> SEQ ID NO 112
<211> Length: 50
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 112
>T10377_node_9
ATGGGTGGTCCACCAGTCAGCTGAAAGAAGAGATGAACTACATCAAAGAT
<210> SEQ ID NO 113
<211> Length: 341
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 113 580 >Z24874_PEA_2_node_21
TCTACCTGGACGGCATGAAGTCCCGAGAGGAGCTCTTCCGTGAAGTCCTGGAAGACATTCAGAACTCGCTGCTGAAC
CGCTCCCAGGAATCAGCCCCCTCCCCGGCTCGCCCAGCCAGGACACAGGGACCCGGACGCGGATGCGGCCACAGAAC
GGCCAGGCCTGCAGCGTCCCAGCAGGACAGCATGTGAGCGTTTCCCTATGGGGGTGTCTGTACGTAGGAGAGTGGAG
GCCCCACTCCCAGTTGGGCGTCCCGGAGCTCAGGGACTGAGCCCCAAGACGCCTCTGTAACCTCGCTGCAGCTTCAG
TAGTAAACTGGGTCCTGTTTTTTTAACTGTTGG
<210> SEQ ID NO 114
<211> Length: 180
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 114
>Z24874_PEA_2_node_4
GGGCCGCCTCCCCCGGGGCGGCCTCCAGGCTGCCGAGACCTATAAAGGCGCCAGGTTTTCTCAATGAAGCCGGGACG
CACTCCGGAGCGCACTGCGTGGTCGCACCCTACCCGGGCTGCCTTGGAAGTCGTCCCCGCCGCCCCTCCGCACCGGC
ATGAAGCTCATCGTGGGCATCGGAGG
<210> SEQ ID NO 115
<211> Length: 77
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 115
>Z24874_PEA_2_node_0
GTTGGCCCTGACCTCGTTGGAAAACGAAGCTCCCCGCAGGGTCCCGGCCTCTAGGGCTGCTGTGCGGGCGGGGGTGG
<210> SEQ ID NO 116
<211> Length: 49
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 116 >Z24874_PEA_2_node_10 CCCCAAGACCAAATAGCAGTTGGGGAAGACGGCTTCAAACAGTGGGACG
<210> SEQ ID NO 117 <211> Length: 57 581 <212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 117 >Z24874_PEA_2_node_12 TGCTGGAGTCTCTGGACATGGAGGCCATGCTGGACACCGTGCAGGCCTGGCTGAGCAGCCCGCAGAA
<210> SEQ ID NO 118
<211> Length: 37
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 118 >Z24874_PEA_2_node_13 GTTTGCCCGTGCCCACGGGGTCAGCGTCCAGCCAGAG
<210> SEQ ID NO 119
<211> Length: 53
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 119 >Z24874_PEA_2_node_1 GCCTCGGACACCCACATCCTCCTCCTGGAAGGCTTCCTGCTCTACAGCTACAA
<210> SEQ ID NO 120
<211> Length: 72
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 120 >Z24874_PEA_2_node_16 GCCCCTGGTGGACTTGTACAGCCGCCGGTACTTCCTGACCGTCCCGTATGAAGAGTGCAAGTGGAGGAGAAG
<210> SEQ ID NO 121
<211> Length: 60
<212> Type: DNA
<213> ORGANISM: Homo sapiens 582
<400> sequence : 121
>Z24874_PEA_2_node_3
CCTGGAGCTATTTCCATTCGGCGGCGGGAACAGGTGCCGGCGCCTCCGCCCCATCCCCAG
<210> SEQ ID NO 122
<211> Length: 91
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 122 >Z24874_PEA_2_node_6
CATGACCAACGGCGGCAAGACCACGCTGACCAACAGCCTGCTCAGAGCCCTGCCCAACTGCTGCGTGATCCATCAGG ATGACTTCTTCAAG
<210> SEQ ID NO 123
<211> Length: 353
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 123
>HUMCDDANF_node_0
GGTTGGATTCCTGGGAGCTTCATCACATTTGGTTCTCAGCTGACTTTATATACTAAAAAATAACTTCCTTTCGCCTG
ACCATGGAGAGGGACTGCCAGGGGTGAAGGCAGCCCTGTCTGAGGCCAGAGGTCTGCCCACGTGGCGGATGAGGCAG
GTGTGAGGCCAGCTTGAGCATCTGGATCCATTTGTCTCGGGCTGCTGGCTGCCTGCCATTTCCTCCTCTCCACCCTT
ATTTGGAGGCCCTGACAGCTGAGCCACAAACAAACCAGGGGAGCTGGGCACCAGCCAAGCGTCACCCTCTGTTTCCC
CGCACGGGTACCAGCGTCGAGGAGAAAGAATCCTGAGGCACGGCG
<210> SEQ ID NO 124
<211> Length: 128
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 124 >HUMCDDANF_node_l0
GCTGCAGCTTCCTGTCAACACTTCTCACATCTTATGCTAACTGTAGATAAAGTGGTTTGATGGTGACTTCCTCGCCT CTCCCACCCCATGCATTAAATTTTAAGGTAGAACCTCACCTGTTACTGAAA 583 <210> SEQ ID NO 125
<211> Length: 127
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 125
>HUMCDDANF_node_2
CtGGGAGACAGGGACAGACGTAGGCCAAGAGAGGGGAACCAGAGAGGAACCAGAGGGGAGAGACAGAGCAGCAAGCA
GTGGATTGCTCCTTGACGACGCCAGCATGAGCTCCTTCTCCACCACCACC
<210> SEQ ID NO 126
<211> Length: 327
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 126
>HUMCDDANF_node_5
AATTTGCTGGACCATTTGGAAGAAAAGATGCCTTTAGAAGATGAGGTCGTGCCCCCACAAGTGCTCAGTGAGCCGAA
TGAAGAAGCGGGGGCTGCTCTCAGCCCCCTCCCTGAGGTGCCTCCCTGGACCGGGGAAGTCAGCCCAGCCCAGAGAG
ATGGAGGTGCCCTCGGGCGGGGCCCCTGGGACTCCTCTGATCGATCTGCCCTCCTAAAAAGCAAGCTGAGGGCGCTG
CTCACTGCCCCTCGGAGCCTGCGGAGATCCAGCTGCTTCGGGGGCAGGATGGACAGGATTGGAGCCCAGAGCGGACT
GGGCTGTAACAGCTTCCGG
<210> SEQ ID NO 127
<211> Length: 132
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 127
>HUMCDDANF_node_8
TACTGAAGATAACAGCCAGGGAGGACAAGCAGGGCTGGGCCTAGGGACAGACTGCAAGAGGCTCCTGTCCCCTGGGG
TCTCTGCTGCATTTGTGTCATCTTGTTGCCATGGAGTTGTGATCATCCCATCTAA
<210> SEQ ID NO 128
<211> Length: 11
<212> Type: DNA
<213> ORGANISM: Homo sapiens 584 <400> sequence: 128
>HUMCDDANF_node_l 1
GTGGTTTGAAA
<210> SEQ ID NO 129
<211> Length: 35
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 129 >HUMCDDANF_node_12 GTGAATAAACTTCAGCACCATGGACAGAAGACAAA
<210> SEQ ID NO 130
<211> Length: 158
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 130
>HUMTROPIA_PEA_2_node_0
TCTCAGTGTCCTCGGGGAGTCTCAAGCAGCCCGGAGGAGACTGACGGTCCCTGGGACCCTGAAGGTCACCCGGGCGG
CCCCCTCACTGACCCTCCAAACGCCCCTGTCCTCGCCCTGCCTCCTGCCATTCCCGGCCTGAGTCTCAGCATGGCGG
ATGG
<210> SEQ ID NO 131
<211> Length: 405
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 131
>HUMTROPIA_PEA_2_node_10
GTGGGACGGGGCTTCCTGGGGGCAGAGTACAGGCGCCGGAGGGATCCAAGACCCTGGGAGTGGGGGGAGGAGCCAGG
GCTGCGAAGGGGGCGGGGACTACGCGGAGGGGCTTCAGGGGCGGAGTTTTGCAGAGGGTCATGCTCGGATTGGTGAC
AGCAGCCTGCGGGCGGAACTCCGTTGCCCTCGGACTTGCTTAGGGATAGATGGGAAGTGCCTATCCAAAGGAAGAGA
CCCAGATTGGTGGATGGGAATGAGGGGCGTGGCCTCCCGTAGACTCAGGGCTCAAGTTGGACGTGGGCCCAAATCTG
GACCGGCTGGGTTTGCTGGGGGTGTCTTGAGGTCCCCTCCACCGTCGTCTCCGAATCCCCCTCCATGATCCTTCCTT
GCTCCATCTCACCCTGGCAG 585 <210> SEQ ID NO 132
<211> Length: 534
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 132
>HUMTROPIA_PEA_2_node_22
GTGGGACGCATGGGCAGCTCGGGTACCTTCGGGGTAGGGTGAGATGGCTGGGACTTGGTCTCTGCCTGACCCCTTGC
AGCTGCTTTTGGCTGCACATCCCAGGAGACCCAGGACAACTGTGAGCCTGGCAGGGCTGGGGCAGAAGGATGAGTAC
AATATAGTCAAGGAAAGCTGTTCTAGGCAGAGGGAACAGCACATGCAAGGCCATGGGTTGGGAAACAGAAAATAAGT
TAGTGAACATGCTCAGGGCATCACATGTTGGTAAATTAGCTCAGGCACTGGCCAGGGAATTGTGATTTGCATGTAGC
TGGACCAGGTTATGCCAGTGGTTTTGAGAGGTGAGGCTGGAGCATATGAGGAGGGGGATTCAGTTCCAGGATTAGAA
GCCTAGACTGGGAGCCTAAGCCGGGAAGAGACTGGTAAGGCCTCGGTACTGGAAGACGAGATAAGGAGAATAAAAAA
GGAGTGTAGGATGGAGGAGTTGGGTGTGCGGGAAATGGAAGGAGAAGTACCCACCCCCTCGTGTGCCCCCAG
<210> SEQ ID NO 133
<211> Length: 144
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 133
>HUMTROPIA_PEA_2_node_23
ATTGCAGATCTGACTCAGAAGATCTTTGACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGATCTC
TGCAGATGCCATGATGCAGGCGCTGCTGGGGGCCCGGGCTAAGGAGTCCCTGGACCTGCGGGCCCAC
<210> SEQ ID NO 134
<211> Length: 42
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 134 >HUMTROPIA_PEA_2_node_l 1 AAAAAATCTAAGATCTCCGCCTCGAGAAAATTGCAGCTGAAG
<210> SEQ ID NO 135
<211> Length: 36
<212> Type: DNA
<213> ORGANISM: Homo sapiens 586
<400> sequence: 135 >HUMTROPIA_PEA_2_node_l 4 ACTCTGCTGCTGCAGATTGCAAAGCAAGAGCTGGAG
<210> SEQ ID NO 136
<211> Length: 44
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 136
>HUMTROPIA_PEA_2_node_15
CGAGAGGCGGAGGAGCGGCGCGGAGAGAAGGGGCGCGCTCTGAG
<210> SEQ ID NO 137
<211> Length: 52
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 137
>HUMTROPIA_PEA_2_node_l 6
CACCCGCTGCCAGCCGCTGGAGTTGGCCGGGCTGGGCTTCGCGGAGCTGCAG
<210> SEQ ID NO 138
<211> Length: 36
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 138
>HUMTROPIA_PEA_2_node_20
GACTTGTGCCGACAGCTCCACGCCCGTGTGGACAAG
<210> SEQ ID NO 139
<211> Length: 54
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 139 587 >HUMTROPIA_PEA_2_node_21
GTGGATGAAGAGAGATACGACATAGAGGCAAAAGTCACCAAGAACATCACGGAG
<210> SEQ ID NO 140
<211> Length: 18
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 140 >HUMTROPIA_PEA__2_node_24 CTCAAGCAGGTGAAGAAG
<210> SEQ ID NO 141
<211> Length: 15
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 141 >HUMTROPIA_PEA__2_node_25 GAGGACACCGAGAAG
<210> SEQ ID NO 142
<211> Length: 20
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 142 >HUMTROPIA_PEA_2_node_29 GAAAACCGGGAGGTGGGAGA
<210> SEQ ID NO 143
<211> Length: 13
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 143
>HUMTROPIA_PEA_2_node_30
CTGGCGCAAGAAC <210> SEQ ID NO 144
<211> Length: 24
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 144 >HUMTROPIA_PEA_2_node_31 ATCGATGCACTGAGTGGAATGGAG
<210> SEQ ID NO 145
<211> Length: 94
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 145
>HUMTROPIA_PEA_2_node_32
GGCCGCAAGAAAAAGTTTGAGAGCTGAGCCTTCCTGCCTACTGCCCCTGCCCTGAGGAGGGCCCTGAGGAATAAAGC
TTCTCTCTGAGCTGAAA
<210> SEQ ID NO 146
<211> Length: 13
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 146
>HUMTROPIA_PEA_2_node_4
GAGCAGCGATGCG
<210> SEQ ID NO 147
<211> Length: 45
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 147
>HUMTROPIA_PEA_2_node_5
GTGAGAGCAGCGGGCTAAGGCGTGGCTGGGACCCCCAGGGCCAGG
<210> SEQ ID NO 148 589 <211> Length: 50
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 148
>HUMTROPIA_PEA_2_node_8
GCTAGGGAACCTCGCCCTGCACCAGCCCCAATCAGACGCCGCTCCTCCAA
<210> SEQ ID NO 149
<211> Length: 34
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 149
>HUMTROPIA_PEA_2_node_9
CTACCGCGCTTATGCCACGGAGCCGCACGCCAAG
<210> SEQ ID NO 150
<211> Length: 1,284
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 150
>HUMSMCK_node_0
TTCCATGCTCTTTAAAAGCCTTATAATTTTCTGGATCTGGGAGCTGGGCTATTTCAGGGTCAATGGATTTATTTCAG
TTGGTGCCTGAACTGACTTGAAACAAGTGTGTGTGGAAAAGAGCTATTTTGAGAAGGAATAAACCGAGACTGCCCTG
ATGATAGAATATGCAAGCTGGTGGGTCTTGACTCCTTAAAGGATTATGAAATTAATTTGATTGGTCCCAATCTTTAT
ATAACCACCCCAATCAGGAAACTTCCCATCCCGCCAAAAGGCCCCCTCACGTGCTCTCCCTGTCAGTACCCCATGCA
AAGGTAAAATAGATGATATTTTTAAACATGGGTCGTGTTTAAAAGAAATGGAAACTCCTTCAGAGAATGAAGGAGAA
CCACACTGGGTAGAAGGTTATTCCTGGGGCTCCACCCCTTGCTCCATCAAGTCCTCTGAGCATGAGCTGGGCTCTGA
GAAGGAAGAGACAGGAACCAATTGGTCATGTCCACGTGGCCTCAGAAGCTGAGTACGTGACGGTCACCAGATGCCTA
GGCAGGCTCCCTTGAAATGGCAGGGCTGCTGTCCAAAATCCTGCTGGGTCATTGCTATTTACAGGCAGCCTTCCCGG
CGTGCGGTGGATATCCCAAGCGGGGCTATTTTTAAGCAGGGCTATGGCCTGCCGTGGGTTAAGCTGGTGTGGACAGA
AAGCGAGATGATCTAGCCATCTACTGCAGGGGGCCTGATCTTGAACAGAAACCTGACTGTAATTGTCCCTGGATCCA
GGTCCCAGACAAAGACGCTGGAAGGAGGTCCCTCCAGCCCCTGGCTCAGGGCCCGGTCAGCTGCTGGAGCCAGGCAG
CTTGAGACATCCTCCTCTCCGACCTTGGCTTGAGGGGTTCATCCTCCAGAGCTCACCAGGGCCCCAAGGCTGGTACA
CCTGAGAGAAGAGAGAAACAAATCCCCCAACAGATGTGCAATTTCACCTGCTGGCCCTTCCATTCTGAGATCCAGAG
CCCTGGCAAAGGAGCCTCCAGGACCAGGCCTGGGAAGCAAGACTGGCTCCGCCTTTTACGTTTCAGAGAAAGGGCAG 590 GTGCTATAAAGGGCCCAGCGCCCACGGGCCTGCCTTCAAGGGTACAGCTGTGGGGGCCGGTGCGCCCGGAGGTCTAC
GCTGGGATTGGTGAGGTCCTCTGGCCCCGCCCCGCCAGGGAGGATTTCCAGGCCGGCCCGACCAGCTCGCCCTGCAT
ACACTTCTTGGCTGTGTGCGCTCAGCAGGACGTGGGAGGCTCCGGCTTCAAG
<210> SEQ ID NO 151
<211> Length: 172
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 151
>HUMSMCK_node_7
ACACTCATCCAAGAGGAAGGATGGCCAGTATCTTTTCTAAGTTGCTAACTGGCCGCAATGCTTCTCTGCTGTTTGCT
ACCATGGGCACCAGTGTCCTGACCACCGGGTACCTGCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGGGAGCAGCC
TAGGCTATTTCCTCCAAG
<210> SEQ ID NO 152
<211> Length: 180
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 152
>HUMSMCK_node_12
CGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCCCCGCCATTTATGCCAAGCTTCGCAACAAGGTGACACCCAA
CGGCTACACGCTGGACCAGTGCATCCAGACTGGAGTGGACAACCCTGGCCACCCCTTCATAAAGACTGTGGGCATGG
TGGCTGGTGACGAGGAGTCCTATGAG
<210> SEQ ID NO 153
<211> Length: 222
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 153
>HUMSMCK_node_l7
ATCACCCAAGGGCAGTTCGACGAGCATTACGTGCTGTCTTCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAG
CCTGCCTCCAGCCTGCACCCGGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGG
GGGACCTGGCTGGCCGCTACTACAAGCTGTCCGAGATGACGGAGCAGGACCAGCAGCGGCTCATCGAT
<210> SEQ ID NO 154 591 <211> Length: 124
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 154
>HUMSMCK_node_22
GCATAATTATGATAAGACATTTCTCATCTGGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAG
GCAATATGAAACGAGTATTTGAGCGATTCTGTCGTGGACTAAAAGAA
<210> SEQ ID NO 155
<211> Length: 199
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 155
>HUMSMCK_node_23
GTAAGATGTTATCTGAGATTTCTGGATATTTATTAAAATAAAATTACCGTATTGTTTGTTCTTGAAAGAAGACACTA
TGGTAACTTCCAAGATGGAGCTAATTTTTTTCTAGAAATCAAAGCAACTGCCGCCTCCCAGGTTCAAGTGATTATCC
CGCCTCAGCCTCTAGAGTAGCTGGGATTACAGGTGCCACCACCAC
<210> SEQ ID NO 156
<211> Length: 135
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 156 >HUMSMCK_node_25
GTAGAACGGTTAATCCAAGAACGAGGCTGGGAGTTCATGTGGAATGAGCGCCTAGGATACATTTTGACCTGTCCTTC GAACCTTGGAACAGGACTACGAGCTGGTGTCCACGTTAGGATCCCAAAGCTCAGCAAG
<210> SEQ ID NO 157
<211> Length: 130
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 157 >HUMSMCK_node_26
GTACTGTTATGTGCCCAGTGGCCCTGATGGGCCAGGATCAGCTCAGATGCGACTGCTTTGTGGAGGAAGAAAACATC ACTGCCCATTCCTTAACCCTTACTTTCTCTATCTACAATATAAAAATAAGAAA 592
<210> SEQ ID NO 158
<211> Length: 126
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 158 >HUMSMCK_node_28
GACCCACGCTTTTCTAAGATCCTGGAAAACCTAAGACTCCAGAAGCGTGGCACAGGTGGTGTGGACACTGCCGCGGT CGCAGATGTGTACGACATTTCCAACATAGATAGAATTGGTCGATCAGAG
<210> SEQ ID NO 159
<211> Length: 376
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 159
>HUMSMCK_node_29
GTAACGTCTCTCTCACTTTCCTAACATGAACTAACAAAATCAGCCTAAGAGAGAATAGAGAAAAGCAAACAGCCTAG
CCGTTTTCACAAAATTCGAGACCTCCTCTTCGCCCATTGAGTCCTGAGTTATGTTAGCTTTTCATTCTGTAACATTA
TTCTTCCATGGGAAATAACTGCATAAAGGGAAACATAATGTGAGCTGAGAATTTATAGGCAAGTATAGGAATTCACA
GTGGGACTGTTGTCACCGACCTGCCATGAGAGCTATTCCAACAATCCTCAGCGAGCAGGAGCTCTGTTATGCTAAAG
GACTGCAGTTTTTTTATTACTGTAAAGTCAGAACATCTATGCTATCCCTCTGAGGGTGGCAAAATAGT
<210> SEQ ID NO 160
<211> Length: 274
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 160
>HUMSMCK_node_32
GTTGAGCTTGTTCAGATAGTCATCGATGGAGTCAATTACCTGGTGGATTGTGAAAAGAAGTTGGAGAGAGGCCAAGA
TATTAAGGTGCCACCCCCTCTGCCTCAGTTTGGCAAAAAGTAAACTTTCCCTTTCCCAATTTATAAATAATCTGTCT
GCTGGTACGACAGACATAAATCTCTACTCTGAGAGTTTTTATACACTTGGAAAAATATAAAATTGTAGATCCTGCCT
ATCTTTACAATAAAACTCTCCTTAATATAAAAAACTTTGCTTT
<210> SEQ ID NO 161 <211> Length: 19 593 <212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 161 >HUMSMCK_node_l 1 CGCAGACTACCCAGACCTG
<210> SEQ ID NO 162
<211> Length: 96
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 162 >HUMSMCK_node_l
GTGTTTGCTGACCTTTTTGACCCCGTCATCAAACTAAGACACAACGGCTATGACCCCAGGGTGATGAAGCACACAAC GGATCTGGATGCATCAAAG
<210> SEQ ID NO 163
<211> Length: 86
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 163 >HUMSMCK_node_l 9
GACCACTTTCTGTTTGATAAGCCAGTGTCCCCTTTATTAACATGTGCTGGGATGGCCCGTGACTGGCCAGATGCCAG GGGAATCTG
<210> SEQ ID NO 164
<211> Length: 665
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 164
>H88495_PEA_3_node_0
GAGTCCCCCTACCCCTCCCAGCTGTATTTATAGCCCTGGCCTAGCCCAGTCCCTGCCCCCAGATCTGAGTTCCAGGG
ACAGGAGGTCATGGGCACGTGTGTTGGGGGCCATGTTCCTTTCCCCCCATTCTAGGGCCTCAATACTGACATCACTC
TCTCACCAGCACGTATCATTCCAGCTGGAAACACCCCGCAATCGAACCCCCAGTCCTTCCGTCCCAGGAGTCTCTCC
CCTCTGATAAGTCTCTTCTGCCTCCCCCAGGTGCCCCAGGCTCCCCCAAAAACCTGCTAAAAGTCTAGCCTTTGTCT 594 TTGCAGCTGCCAAACGTGAGCTTGTTGGTAGTTCAAAGTCAAGTCCCTTGGCCACCGTCTCCTGGCCAGGGAGAGAC
CCCTCACTGGTCCCCTCCCCAGCTGGGAGGAGGAGGAGCAGGAGGCAGGCAGGCGGGGACTGACCCAGAATAACTCA
GGGCTGAGAGTAAATTTAGCTGGAGAGAGGGGAGGGGAAGGACCCTATTGGCTGGGGAATGGGGAGGGAGGGCCCCA
GAGGGGGGTCAGGGGGCTCCGGAGACAGCCTCAGAGGGGTGTCCAGAGCCAGGCAGCAAGGACCAGAGGAAGGTGGA
CAGAGACCGAAAGGACAAAGGAGAGACACAGAGAAAAAAAGAGACCAAC
<210> SEQ ID NO 165
<211> Length: 513
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 165
>H88495_PEA_3_node_l
CCCAAAGGGACAAAGACCCCAACGTTTGTCCACATTGCCGCAGAGGCAGCTGGAGCCAGTGCTGCCTGTCCGTCCCC
ATGGGCCACCATAGGCCATGGCTGCACGCTTCTGTCCTCTGGGCTGGGGTGGCCAGCCTGCTCCTCCCCCCGGCCAT
GACCCAGCAGCTCAGAGGGGATGGGCTGGGCTTCAGAAACCGGAACAACAACACTGGAGTCGCCGGGCTCTCCGAGG
AGGCATCAGCAGAGCTTCGCCACCACCTCCACAGCCCTAGAGACCATCCAGATGAGAACAAGGATGTTTCCACAGAG
AATGGGCATCATTTCTGGAGCCACCCAGACCGTGAAAAGGAGGATGAAGATGTCGCCAAGGAATATGGGCACCTACT
CCCAGGCCACAGGTCCCAAGACCACAAAGTCGGAGATGAGGGTGTCTCAGGTGAGGAGGTCTTTGCAGAGCATGGTG
GGCAGGCCCGTGGGCACAGAGGCCACGGGAGTGAAGACACGGAAGACTCAG
<210> SEQ ID NO 166
<211> Length: 437
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 166
>H88495_PEA_3_node_4
GAGCCACAGCCATCAAGACGAGGATGAGGATGAAGTTGTGTCCAGTGAGCATCACCATCATATCCTCAGGCATGGAC
ACCGAGGCCATGATGGGGAAGATGATGAAGGAGAAGAGGAGGAGGAGGAGGAGGAGGAGGAAGAGGAGGCCTCCACT
GAGTATGGACACCAGGCCCACAGGCACCGAGGCCATGGGAGTGAAGAGGATGAGGATGTCTCAGATGGACACCATCA
TCATGGCCCCAGCCACAGGCACCAAGGCCATGAAGAAGATGACGATGATGATGATGATGATGATGATGATGATGATG
ATGATGATGTCTCCATTGAATATAGACACCAGGCTCACAGGCACCAAGGCCACGGGATTGAAGAGGATGAAGATGTC
TCAGATGGACACCATCATCGCGACCCCAGCCACAGGCACCGAAGCCATGAAG
<210> SEQ ID NO 167 <211> Length: 517 <212> Type: DNA 595 <213> ORGANI SM : Homo sapiens
<400> sequence : 167
>H884 95_PEA_3_node_9
TGAACGTTGGCACCAGGGTCCCCAACATGTCCACCATGGCCTTGTAGATGAGGAAGAGGAAGAAGAGGAGATCACAG
TCCAGTTCGGCCACTATGTTGCAAGCCACCAACCTCGAGGCCACAAGAGTGATGAAGAGGACTTCCAAGATGAGTAT
AAAACAGAAGTCCCTCACCATCACCACCACAGAGTCCCCAGGGAGGAAGATGAGGAGGTCTCTGCTGAGCTTGGCCA
CCAGGCCCCCAGCCACAGGCAAAGCCACCAAGATGAAGAAACTGGCCATGGTCAAAGAGGGTCCATCAAAGAGATGA
GCCATCACCCCCCAGGACACACAGTGGTCAAGGATAGAAGCCATTTGAGGAAGGATGATTCTGAGGAGGAAAAGGAG
AAGGAAGAGGACCCCGGCTCCCATGAGGAAGACGATGAAAGTTCAGAGCAGGGAGAGAAAGGCACCCATCATGGCAG
CCGGGACCAGGAAGATGAGGAGGATGAGGAGGAAGGTCATGGCCTCAGCCTGAAC
<210> SEQ ID NO 168
<211> Length: 132
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 168 >H88495_PEA_3_node_13
GAAGAAGACGAGGAGAGGAGGGAAGAGAGGGCTGAGGTTGGGGCCCCACTGAGCCCAGACCACAGCGAGGAGGAAGA GGAGGAGGAGGAGGGGCTGGAGGAAGATGAGCCCCGCTTCACCATCATCCCCAAC
<210> SEQ ID NO 169
<211> Length: 251
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 169
>H88495_PEA_3_node_l 9
GTGAGACCTCACCTCACACTCAAGGCTCCACTGGGCCTCAGGATGCACCGGGACCCTCTGAGGACCCCCAGCCCTAA
ATCCTGGCCTCTGACCCAACCCCTTACCCCTGATGCAACCTTGACTCCACAAGCGATCCTGACTCCAACCTTAACCT
AGACCTAGCCTCTGGTCCGGGTCTGGTCCCGGCCCCATCCTAACTCCGCCCCCGGCCACGCCCCACGCTCACTCTCT
CTCCCCGTCCCCGCCTCCAG
<210> SEQ ID NO 170
<211> Length: 327
<212> Type: DNA
<213> ORGANISM: Homo sapiens 596
<400> sequence: 170
>H88495_PEA_3_node_21
GTGAGCATGGGCGGGGCCCTGGAAAAACCTGAGGAAGGTGCCGGGCCCAGCGTGGTGAATCCTGGTGGGGGCGGAGC
CTGGCCCGGTAGGCTGGTGGGGCGGGGCTAAGAGGGGAGGCGTGGCCAAGGCTCTGAGCACGTGGGCCGGGGCCTGG
CTCGAGGAACACCAGGTGGAGTTGCTGGAGCCAAGGGACAGAAATGAGTGGAGGGTTGAGATGCGGGCTTAGAGCCT
AATGGGCGAGGCCAACTCAAGTAGGAATCGAAGGGGCGGGGCTACTGGAGAACGGAATCACCCAGAACGAAAAAGGG
GTCCGGTAGAAGGGATTCA
<210> SEQ ID NO 171
<211> Length: 242
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 171
>H88495_PEA_3_node_26
GGCCCTGGCAGACATGCTGGAAACGCCGGAACCCTGACCCAGTCGCTCGACTGCGACGCAGGTGTACCTCCCCCTGC
CTTCCAACCCCTTTCCACGAGCTATATTTATTTCTCCGAATAAACGTGCTCCCCGAAACCTCATTGTCAGACGTGGG
GTCTGGGAATCTCAGGGCATCGGGGAATGCGGGTAGGGTCTAGAGACCTGGACCTAGACTTGAGGGATGAGGGGCCT
GGACTCCTGGC
<210> SEQ ID NO 172
<211> Length: 31
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 172
>H88495_PEA_3_node_2
CTGAGCACAGGCACCACCTCCCCAGCCACAG
<210> SEQ ID NO 173
<211> Length: 30
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 173
>H88495_PEA_3_node_5
AAGATGACAATGATGATGATGATGTCTCCA 597
<210> SEQ ID NO 174
<211> Length: 107
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 174 >H88495_PEA_3_node_6
CTGAGTATGGACACCAGGCCCACAGGCACCAAGACCACAGAAAGGAAGAGGTTGAGGCTGTCTCAGGTGAACACCAC CATCATGTCC
<210> SEQ ID NO 175
<211> Length: 10
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 175 >H88495_PEA_3_node_7 CTGACCACAG
<210> SEQ ID NO 176
<211> Length: 45
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 176
>H88495_PEA_3_node_8
GCACCAAGGCCACAGAGACGAGGAAGAAGATGAGGATGTGTCCAC
<210> SEQ ID NO 177
<211> Length: 18
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 177 >H88495_PEA_3_node_10 CAGGAGGAGGAAGAAGAG 598
<210> SEQ ID NO 178
<211> Length: 9
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 178 >H88495_PEA_3_node_ll GAAGACAAG
<210> SEQ ID NO 179
<211> Length: 15
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 179 >H88495_PEA_3_node_12 GAGGAGGAGGAGGAG
<210> SEQ ID NO 180
<211> Length: 64
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 180 >H88495_PEA_3_node_14 CCACTGGACAGGAGAGAGGAGGCTGGAGGTGCCTCCAGCGAGGAGGAAAGCGGTGAGGACACAG
<210> SEQ ID NO 181
<211> Length: 71
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 181 >H88495_PEA_3_node_16 GTCCACAGGATGCTCAGGAGTATGGGAACTACCAGCCAGGGTCCCTGTGTGGCTACTGCTCCTTCTGCAAT
<210> SEQ ID NO 182 599
<211> Length: 69
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 182 >H88495_PEA_3_node_18 CGATGCACTGAATGTGAGAGCTGTCACTGTGATGAGGAGAACATGGGTGAGCACTGCGACCAGTGCCAG
<210> SEQ ID NO 183
<211> Length: 55
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 183 >H88495_PEA_3_node_20 CACTGTCAGTTCTGCTATCTCTGCCCGCTGGTCTGCGAAACGGTCTGCGCTCCAG
<210> SEQ ID NO 184
<211> Length: 8
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 184 >H88495_PEA_3_node_23 GAAGCTAC
<210> SEQ ID NO 185
<211> Length: 29
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 185 >H88495_PEA_3_node_24 GTTGACTATTTCTCCTCGTCCCTTTATCA
<210> SEQ ID NO 186 <211> Length: 276 <212> Type: DNA 600 <213> ORGANI SM : Homo sapiens
< 400> sequence : 186
>Z36249_PEA_3_node_0
ACATATTCAGCAGGGTTAGCTTGTCCTCCCCTCCCTCTTCAGCTTCCCAGACACTGAGTCTGGAATGAAAATTCACC
TGCCTCTGAGTTGGCTCCTAATGGGGGTGGGAGTGTTACTTCGGTTCCCAGGTTGGAAGATTATCTCACCCGGCCCC
AGCTATATAAGCTGACCGGTGTGGAGGGGCCCAGCAGGGCCAACTCCAGGGATTCCTTCCACGACAGAAAAACATAC
AAGACTCCTTCAGCCAACATGATGGTACTGAAAGTAGAGGAACTG
<210> SEQ ID NO 187
<211> Length: 180
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 187
>Z36249_PEA_3_node_3
GTCACTGGAAAGAAGAATGGCAATGGGGAGGCAGGGGAATTCCTTCCTGAGGATTTCAGAGATGGAGAGTATGAAGC
TGCTGTTACTTTAGAGAAGCAGGAGGATCTGAAGACACTTCTAGCCCACCCTGTGACCCTGGGGGAGCAACAGTGGA
AAAGCGAGAAACAACGAGAGGCAGAG
<210> SEQ ID NO 188
<211> Length: 138
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 188 >Z36249_PEA_3_node_5
CTCAAAAAGAAAAAACTAGAACAAAGATCAAAGCTTGAAAATTTAGAAGACCTTGAAATAATCATTCAACTGAAGAA AAGGAAAAAATACAGGAAAACTAAAGTTCCAGTTGTAAAGGAACCAGAACCTGAAATCATT
<210> > SEQ ID NO 189
<211> Length: 685
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 189 >Z36249_PEA_3_node_ll GTAAGACTCATGCAAAGCACTGCAAAATCCAGCTCATTAATTTTATGTTTCTTATGCTTTACTCCAGTCTTGCTAAT 601 ATAGTGCCAAAGTCCTTCCACCTGAAACAGTTTCCCCAGCTGTTGCTGTGTATGCCAGGAGCCTAATAGGAGAGTTC
AGTGGTCCAAAAAATAAATAGATATTAGATCAGTGATACGGATTGCATTGTTTTTTGCACTCATATACATCTGGCTG
ATTTTTCAGTTTTTCTTTAACTTCTTAGATTCTTGGGATAAGACTTTTAATGTGGGCCAAAAAGTCACCTTTAGAGA
TATATTATTAGCATCATCTTTGATTAAAACCAAGCACGTCAACACTAGATAAGAAATCTGGAGATTGGAGTTCAGGG
GCCAGTTGTACCACTACTTGGCTATTTGGTTTTGAGCAGCTAATTTGCATCCTCTGGGCTGTGGTTTCCTTATCTGT
AAACATGGGGCATTGGAGTGAAATAACGCCTAAAGTTGTTCCAGCTCTAATAGTTCATTAGCCCATTCAAATAAAGC
CAATTTATCAGAAATCACTAATCTTTTTGTATTCTTTCCCCCATGAAGTGAAATTGGGGACCGCTTCTGAAGTTGAA
CTAAAAACATGTCTCCCATTCTCCTAAAAATGAATGGAAACTTTTTGATAGTCTAGCAACAGTCCCAGA
<210> SEQ ID NO 190
<211> Length: 671
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 190
>Z36249_PEA_3_node_l4
GTAAATATATTTCTTTGCTTGGGAATGAGCCAAAAGAAGTAGACTATATGAAGCTCCGGAAAACCTCCAATGCAAAA
CCGAGCTGATTGGATTGAAAATTGATCTGAGAGAACTAGGCAAAAGCTCATTTCTCCAAATAAAGGAAAGTTGGGAG
ATGAGAGTAGGTCATGTGAAAATATTTTCCATACATACTGAAAATAGAGGAATATTTCAGGGAAAAGAAGGAAGTGA
AAGCTGTTAAACTGAATTCAATATCCTCATCAGCGAGTTAGTCATTCATTTTCGACACTTGCCTTTCAACAGCCTTG
TCCCTCCATTGTTCACAGGGCAGCCTGCTTATGGTTGGCTGCCAGCAACATATACGAATTCTCTAGCTGCACACTTT
ATATGATAGATGCCAATTGCTACCAATGAGATTTGGGGCTAGACTGCATATGAAATGAATTGCATCTATGGAAAGTA
GCTGCTATTCAGACCTCAATAATTCAATCACTGTGATTTCTACGAAGACCAGTATGCAGCATAATTTATGAACTGAA
GATTGAGCTGGGAAAATTCTTTATGTATTTAAATGCAGCTCATTTTGACTTTATAGCAAAGCGGCAACGGGATATCA
AAGAAATCCAAGGGACTTGGCCAAAATTGAATCCAAAACATAAACACATTGAAAA
<210> SEQ ID NO 191
<211> Length: 1,074
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 191
>Z36249_PEA_3_node_24
GCTGGGAAGACGCCGATGGATCTGGTGCTACACTGGCAGAATGGAACCAAAGCAATATTCGACAGCCTCAGAGAGAA
CTCCTACAAGACCTCTCGCATAGCTACATTCTGAGGCAAACGACAGACTCTTAATCAGTAAATGTTCACTGGCATTT
TGAAGGCATGGCCCAAGAGAAGAGACACTAGCCATAAAATCTAGTTTCTATTTATCAACGTGTTGTGAAGATGTACC
TAATGAAGTTTTGAGAAAGCACAGGGTTATAGGTGTTTAAATTTCCTTTAGTGAAACTCTTATTTATTTTTATGTAT
TCCTGTTTATTTATTTACTGCCACGCTACTGATATTCAGACCTTCATGATCATCCATCTGGTGAGCAGAGCTTCATT
TGTATATAACACTTTCAGAGCCTTCCCACCCATAGGTAGTTCTTAAACCAGGTGAAAGAGCAAAGTTCAAGTGCCTA 602
CTTATGTGTCATTCGCTCATGTAAGAGTTTTTAAGAGAGGGCTGATTATCACAGCCCTCTTTTCTCCTGAATTTTTA
ATGCAGAAGTTTGAATGAAGCAAGGGAAGGCATGTAGGGACAGGAAAGGAAACAATGGAAGGAAAGTGATTCTGTGA AAAGGACAGTGAAGCCAGCTATTTTACCCCCAGGCTGGATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACCGAGTA CACAGAGTACCCAAGTGAAGAGAACGTCATGAGTGTAAGTGCAAATCAGTGGAAGGAGCGGCAAACTGGGACATGCA GAATTGAATTTGCTCAAAAAAGATGAAAGGAAATGCAAACTGTAAATGTATAAATGTATATTGTATTGTATGTACAT TTTATATTCATAATAAAGGCAATCAAACTCTAAACCTCTAAGTCCTTCTATAAGTGTGGTGGAAATGTCCTATGTGA AAAAAAAAGCTATATAGGAGGGTTTTTTTTTTCCATTGTTTTCCAAGTTTTGCAGATTAGAAATGTCCCGTACAACA GCACTCCCAGTATTTAATATGTATACAGATCACCTGGGGATCTGGTTAAAATGCAGATTTCTGATTCAGCTGG
<210> SEQ ID NO 192
<211> Length: 108
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 192 >Z36249_PEA_3_node_l 0
ACGGAACCTGTGGATGTGCCTACGTTTCTGAAGGCTGCTCTGGAGAATAAACTGCCAGTAGTAGAAAAATTCTTGTC AGACAAGAACAATCCAGATGTTTGTGATGAG
<210> SEQ ID NO 193
<211> Length: 99
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 193 >Z36249_PEA_3_node_13
TATAAACGGACAGCTCTTCATAGAGCATGCTTGGAAGGACATTTGGCAATTGTGGAGAAGTTAATGGAAGCTGGAGC CCAGATCGAATTCCGTGATATG
<210> SEQ ID NO 194
<211> Length: 99
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 194 >Z36249_PEA_3_node_17
CTTGAATCCACAGCCATCCACTGGGCAAGCCGTGGAGGAAACCTGGATGTTTTAAAATTGTTGCTGAATAAAGGAGC AAAAATTAGCGCCCGAGATAAG 603
<210> SEQ ID NO 195
<211> Length: 99
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 195 >Z36249_PEA_3_node_19
TTGCTCAGCACAGCGCTGCATGTGGCGGTGAGGACTGGCCACTATGAGTGCGCGGAGCATCTTATCGCCTGTGAGGC AGACCTCAACGCCAAAGACAGA
<210> SEQ ID NO 196
<211> Length: 99
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 196 >Z36249_PEA_3_node_21
GAAGGAGATACCCCGTTGCATGATGCGGTGAGACTGAACCGCTATAAGATGATCCGACTCCTGATTATGTATGGCGC GGATCTCAACATCAAGAACTGT
<210> SEQ ID NO 197
<211> Length: 319
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 197
>Z25377_PEA_l_node_5
GAATCTGCCGGTGGGGCGTGAGCGAGAAGCCACCAAAACATGAGCTAGGACAGCCTTCTCAAGAAGATTCTGCCAAC
TCAAAAATATTATTCTTTTTTTTTTTTTTTTGCTGTTGTTTCTGAGAAACTAGGTGTCTTACCATTTTAAAATTTCA
TATTTTATTTAAAAGGAAACCAGTGAATTGAAAATGAGACTAAATATCGCTATCTTCTTTGGAGCTCTCTTTGGTGC
TTTGGGGGTGTTACTCTTTTTGGTGGCTTTTGGATCGGATTATTGGCTTCTTGCAACTGAAGTGGGGAGATGTTCAG
GTGAAAAGAAT
<210> SEQ ID NO 198
<211> Length: 405
<212> Type: DNA
<213> ORGANISM: Homo sapiens 604
<400> sequence: 198
>Z25377_PEA_l_node_12
GTCTTCTTTGATTCCTCATGGCAAACCAAATCCAGCAGCACATCAAAAAGCTTATCCACCATGATCAAGTGGGCTTC
ATCCCTGGGATGCAAGGCTGGTTCAATATATGCAAATCAATAAATGTAATCCAGCATATAAACAGAACCAAAGACAA
AAACCACATGATTATCTCAATAGATGCAGAAAAGGCCTTTGACAAAATTCAACAACACTTCATGCTAAAAACTCTCA
ATAAATTAGGTATTGACGGGATGTATCTCAAAATAATAAGAGCTATCTATGACAAACCCACAGCCAATATCATACTG
AATGGGCAAAAACTGGAAGCATTCCCTTTGAAAACTGGCAAAAGACAGGGATGCCCTCTCTCACCACTCCTATTCAA
CATAGTGTTGGAAGTTCTGG
<210> SEQ ID NO 199
<211> Length: 138
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 199 >Z25377_PEA_l_node_15
TTTACCGTGGTTTCTGGGCAGTCCTGATGCTCCTGGGGGTAGTTGCTGTAGTCATCGCAAGCTTTTTGATCATCTGT GCAGCCCCCTTCGCCAGCCATTTTCTCTACAAAGCTGGGGGAGGCTCATATATTGCTGCAG
<210> SEQ ID NO 200
<211> Length: 188
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 200
>Z25377_PEA_l_node_17
GCATCCTATTTTCATTGGTGGTGATGCTGTATGTCATCTGGGTCCAGGCAGTGGCTGACATGGAAAGCTACCGAAAC
ATGAAAATGAAGGACTGCCTGGATTTCACCCCTTCTGTTCTGTATGGCTGGTCATTTTTCCTGGCCCCAGCTGGGAT
ATTTTTTTCTTTGCTAGCTGGATTACTATTTCTG
<210> SEQ ID NO 201
<211> Length: 3,478
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 201 >Z25377 PEA 1 node 18 605 GTTGTTGGACGGCATATTCAGATACATCACTAAATCAACTGTTGCCACAAGTATTTTCTTGAGAGATTTTAAAACAA
GGAATACTTTTTTTCCATTTTGTTTCATTGATCCCAGCATAAAGTTAGTAGATATAACTTTTTAGTTGCTATTCAAA
TTAATCATTTTACTAAAATTTTCTTCAGTAAGAAGGTCCTAGAATCTCTCCAGACACCAGCAAGCCTCTATCTTGTC
TAAGTGCTGTCAAGGACCTAGTTCTTTAGGGAATAGGTAAACAGGTCTCCCTTTCATTGAACATGTTAGAGTTCATG
CAGGTCGCAAAGGCCTGATAATAGCTTAATACCATGACATGGGGAAAATCTCGATAGATTTGGCTTAAAGTCTCCTT
GGCATTCACTTCTGCTAATTAAAAAAAATCCTTGAAGAATAATTAAGAATGGGCAAGGTTGTCAGAGAATTTATTTT
GTTTCTTGCCCACACAGATAATATCCACATACACATTCACTGGCTCTTGTGAGCAAATGAATTTAAAAATAGACAGC
AGTTGTTCTAATTAGTGGGAGCCATGTACTCACCAGTTAAAATGGGCCACAACAAACAAGACTGAGAGCATGTACTT
ATCTTGCTTTTTCACCAACAGTGGTTTGGTTACCTAGTTTTATTCACTTAATTGTGCATGCTTACATAAACTTTAAA
CTACATTTAAAACTAGCAAATCTGCATACCAAATTATGTATAACGTAGATTGAATTTTTATGAACTTAAAGTGAGTT
AATTGTATAATGTAATATTGTTTAAAATATGTAAAAACCAAGCATTTCCGCTTGGTCCATAATTCTATTTGATATTT
TAAAATTCTCATTTAAAAATTATATTGCTATCATTCAGCATGTGAAAATTTATTGATAAAATGTGATTTTAATATTT
TTTAGATATAAACTTTCAACGTACTTCCATATGAGGATTATAATAGCCCTGCTTTATTAAAGACCATAAAATATTAA
CTTTCCCCAAGATGTTATGGGTTCCAGTTCTTCTGATCATTTGATTCCTTTAATTACTGTCCCTCAATTTCTTCATC
TTTACAATAGATATATTAACATTTACAGATCGACTATTTCCTTTAACCTCCTAGAAGAAAGTTTTTGTGGGGAAAGA
TGATTCTGTATTATTCAGTAGCATAGACATTTTGCATATCAAAGATGTTCATTTGGCACTAATGTTGATTGAAATCA
AATCCATCTGAGATGCCTAGCTCGTATTTGCATTCTGGAAGCCTCCATCGCAGGGGAGCTCGGCAGGGTATGTGAGC
TTTGTTGGAGGTGCGGTGTTTCATTCTGCAGCTGTTGTGAGGACAGAGAGGCATGGCCCACAGGCAAAAAAAGTCAC
CACCCAGAAGATGCTCTGGGATAGAGGAACTGCTCCTTTTCATCAGCTCTTCCAATGCCGTGGGAGAGGTGATCCCA
GTCTTCTCTGTACATCTTGTGCTTTTCCATTAAGACTTGTTCCAGTGGGAAGGAGCTTTGGAAAAATTGCAAAGGTC
TGAATCTTCAGGGCATTTTCATGACAGGACTTGCCAATAATAATAATAATAATAATAATAATAATAATAATAATAAA
GCTCCAGAGGCCTAACTGGTTTCTCAAGTCATTTCAGTGATATCATTGAAACGTTTTTGTGGTACTTCCCTTTGTCT
TTCACTGTTTCATTTTTATATTGCTTCATTTACTTCTTTGCTTTTGGCTTTGTTATTAGAAAAAATAATTATGAGGT
CTGTTGTGCATGTTGACTGTGATATTAAGTTATGGCATGCCATTAAGTTTTCCAGACGATGTTGGATGTATCTGATT
AGTTCATGTCATCTGTAAATACAATTCTTTTTTGTAGTACTTTGGAATGGAGCCTTTTTCTGGTGTACTGTATGCCA
TTTAAGTTTCACATACAAGCTGCTTTCGGCAAAGGCTTGAATATTTATAAATTTCAGATGGTTATCCTCACTTTATA
GTACACTTAAGTGGCTACCATATATTTTTTATATGACAATTGGCTGAATAGCTGATGTGTATGACACTTTTACACAG
ATTTGCACTTTGGAACTATTTTATAGTTGTAATGCATCAATCAAATACATTTCAAGCACATTTCTTGATCAATTTAC
CAGCAACCCTCTGAAGGAATGAAGGAGAGTTGTGATTGCTATGTCAATGAGTGAAATATACTTAAAAATGGCAGAGT
TATATAGTACATTATTGTAGCAACCTTATATCTGATTTGAGATACTGTGTTGCCAAATGTCCATGTTATGTTTATTT
CTCTATTGGTTGTATTTATTAATTTTTAGAAGCCTTTAAACTGTGTTAGAATCTTTTTGAAAAATGTTGATTTTGCA
TCATAAAGTTTCAATTTATCAAGGATATCTTTTCAGTTACACTTTTAGAAAGAGTGAATAAAAAGGGCAGTGAGTTA
TGCTCTTGGACTTGGTGAAAGCTATCATCTCTCCATATTGTATTTGTTCAGCTGGTTTAATTCACTCAGGTGGATGA
TTGCACATACATTGGAATTGGCTGGAGAGACTACACAGAGAAGTTTAATGATCGTGTACAATTTGAGGGTTGATGGT
AGGGCTTTCTAAAAAAAGTAATATCAAGTGTGTTGTTAGTATTCATTTAGTCATTTTTATTACTAATCTATAAATAT
ATTTATTAAATTTGAAGATTAAATGGAATTATAAAGGAATATATTGGAGGAAGTGTCAGTGTTGGTAATTATTCATC
TATTTATCTGTCTATCATCAATATATATGGGTGCATGTCTGTGTATATTTGTGTGTATGTAAGTGTGCATGTGTATT
ATATGTTTGGGTAGAAAGAGATACATTGAATGGTATAAATCAATATATTTGAGCTAAGCAAGTTAAAAAAAAATCAG 606 TTATCTTTGGGAACAGCAATCTATTATTGTTGTTTCCCTGAGTGCCACTTTAACTGTTTCACTCAATGGATGGTGGT
TTATTCAGTTCAACACGTAATTTGATTTCTATTTTCTTAAAAGTAACCATGTTGGACTTACAAAGAGACTTAGAATG
TCAGAGGTGTTAGGCAGATATTGGATACCAGTAAAATTGGCTGGATATGTCTGAAGGTCGGTGGAATTGTGAGAAAG
ACCAATGGTGATGGGGTTACATTGAAGAAAATATAAGATGAGCTAAATCAAAACCAGATTTGATTTTTTTGGGACTC
CACCAGAAGTGGAAACTCATAAACAAGAGATGAAACAGAAAACTACATTTTTATTGATTGTATGAAGGAGTTAAATA
TATGGAGACATTTCCTCAGTGATGATCAAGGGTAGGTGGGGAAATTCCAATAAGAATGTAGGATGACAATACCTTAG
ATATGTTGAAAACCAAGGAGGATGGGGATATAGTATCTTTCGTATTATAATAAGCATAAAGTTAGCAAAGGGACATT
TAATTTGGTTAGC
<210> SEQ ID NO 202
<211> Length: 427
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 202
>Z25377_PEA_l_node_22
ATGGAATTTCTTCTCTCTGTTACTCAAGCCTCTCAAAGTCCTTATTGTCCCAGCCTCTGCGTGAAACGTCTTCAGCC
ATCAATGACATCTCACTCCTTCAAGCCCTTATGCCACTGCTGGGATGGACCAGTCACTGGACCTGCATTACAGTGGG
CTTATATTGACCTTTACCTCTACACTTGTATATAACTCGTTTTCCCATTTAGTTGCAAGACACTTGGAAGCACAGAC
CAAGGCTTACATTTGTGTTTTAATGTTTTTCTTGTAAATGCTTTATGCCTAAATGTTTCTGTACTACTCTTCTTTCC
AAATCCTTATTGTTTAAAAGTTTCTCTCCTACTATACCATGCCTTATAAATATTGATTGAATGAATGGATGAAATGC
ATACCTGCTTATATTTCTAATTAAAGGCAATTTGGGATTATA
<210> SEQ ID NO 203
<211> Length: 342
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 203
>Z25377_PEA_l_node_24
TTTCTGTGGGTCAAGAGTGTGGAAGTGGCTAAGCAGAATGAGTCCAGCTCAGAATCCCATGAGTCTGCTAATCAAGC
TATTTTCTGGGGTTGCAATCATCTGAAGGCCCAGCTGGGGCTAAAGAACGCACTTTGCAGCTCGCTTTTTGCCTGGC
TCAGAAGATCCATTTCCAGACTCACTTACACTGGCAGGCCTCAGTTCCTTGCCATGTGAATCACTGGGATGGGCTGC
CTGGACCTCCTCAGGATACAGCAATTGCTAATAAAAGAGGTTTAAGGGGAACCAGAGAACTAGACGATAAAAGAAGT
TGGCTAACATGAAAGCCCCACCTCCAACATTGGG
<210> SEQ ID NO 204 <211> Length: 104 607 <212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 204
>Z25377_PEA_l_node_0
AGAGAGGGGGCGGGTGCTACCTGGCAGCTCCGCGGGTGCGTGGCCGGTGCTGGCTGGGAGTTCTGGTCTCAGGCAAG
GTGGGGACTGGGCACATCATCAATACG
<210> SEQ ID NO 205
<211> Length: 95
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 205 >Z25377_PEA_l_node_7
ATAGAGAACGTCACTTTTCACCATGAAGGGTTCTTCTGGAGGTGTTGGTTTAATGGGATTGTGGAAGAGAATGACTC CAATATTTGGAAGTTCTG
<210> SEQ ID NO 206
<211> Length: 5
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 206
>Z25377_PEA_l_node_8
GTACA
<210> SEQ ID NO 207
<211> Length: 99
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 207
>Z25377_PEA_l_node_10
CCAATCAGCCACCGTCCAAGAACTGCACACATGCTTACCTGTCTCCGTACCCCTTCATGAGAGGCGAGCACAACTCG
ACCTCCTATGACTCTGCAGTTA
<210> SEQ ID NO 208 608 <211> Length: 110
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 208 >Z25377_PEA_l_node_20
GAATCTAGAAGATGGGGGGATGGAAGTGAAGTGGAATGTAAAAACGTCTGCCAGTGCCCCATGGTCTCCAACCCACT TTCAGATGCACCGTCTCATTTCAACAGATATAG
<210> SEQ ID NO 209
<211> Length: 328
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 209
>HSACMHCP_PEA_l_node_2
GCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCGCCAGGCTAAGGTGGAGAAGCTGCGCTCAGAC
CTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCCGGCGGGGCCACGTCCGTGCAGATCGAGATGAA
CAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCACGCTGCAGCACGAGGCCACTGCCG
CGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGGGCGAGCAGATCGACAACCTGCAGCGGGTGAAGCAG
AAGCTGGAGAAGGAGAAGAG
<210> SEQ ID NO 210
<211> Length: 214
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 210
>HSACMHCP_PEA_l_node_20
GGGAAGCACCAAGATGACCGATGCCCAGATGGCTGACTTTGGGGCAGCGGCCCAGTACCTCCGCAAGTCAGAGAAGG
AGCGTCTAGAGGCCCAGACCCGGCCCTTTGACATTCGCACTGAGTGCTTCGTGCCCGATGACAAGGAAGAGTTTGTC
AAAGCCAAGATTTTGTCCCGGGAGGGAGGCAAGGTCATTGCTGAAACCGAGAATGGGAAG
<210> SEQ ID NO 211
<211> Length: 122
<212> Type: DNA
<213> ORGANISM: Homo sapiens 609 <400> sequence: 211
>HSACMHCP_PEA_l_node_22
ACGGTGACTGTGAAGGAGGACCAGGTGTTGCAGCAGAACCCACCCAAGTTCGACAAGATTGAGGACATGGCCATGCT
GACCTTCCTGCACGAGCCCGCGGTGCTTTTCAACCTCAAGGAGCG
<210> SEQ ID NO 212
<211> Length: 157
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 212
>HSACMHCP_PEA_l_node_25
ACCTACTCGGGCCTCTTCTGTGTCACTGTCAACCCCTACAAGTGGCTGCCGGTGTACAATGCCGAAGTGGTGGCCGC
CTACAGGGGCAAGAAGAGGAGTGAGGCCCCGCCCCACATCTTCTCCATCTCCGACAACGCCTATCAGTACATGCTGA
CAG
<210> SEQ ID NO 213
<211> Length: 269
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 213
>HSACMHCP_PEA_l_node_43
ATGCTGACAAGTCGGCCTACCTCATGGGGCTGAACTCAGCTGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAA
GTGGGCAACGAGTATGTCACCAAGGGGCAGAGCGTGCAGCAGGTGTACTACTCCATCGGGGCTCTGGCCAAGGCAGT
GTATGAGAAGATGTTCAACTGGATGGTGACGCGCATCAACGCCACCCTGGAGACCAAGCAGCCACGCCAGTACTTCA
TAGGAGTCCTGGACATCGCTGGCTTCGAGATCTTCGAC
<210> SEQ ID NO 214
<211> Length: 171
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 214
>HSACMHCP_PEA_l_node_45
TTCAACAGCTTTGAGCAGCTCTGCATCAACTTCACCAACGAGAAGCTGCAGCAGTTCTTCAACCACCACATGTTCGT
GCTGGAGCAGGAGGAGTACAAGAAGGAGGGCATTGAGTGGACATTCATTGACTTTGGCATGGACCTGCAGGCCTGCA
TTGACCTCATCGAGAAG 610
<210> SEQ ID NO 215
<211> Length: 819
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 215
>HSACMHCP_PEA_l_node_46
GTGCCTCCTTGGCCTCACCACCTATGCCCCCTCCTCTGCCATCCAGACAAAGTGGTGGCTGAGTCCCTTCTACACCC
AAGAAACTAGAGTCCCAAGAATCCCAGGCCTTTCTCCAGGCCCAGCTTCTCCCCACTGTGAAGTCATGGGCATGAAC
AGGATGATCCCCCCACTCTTCCTTTCCCAGGACCTTGCACTTTATGCCCCTTTGTGGTGGTCCCCTCAGTGTCTTAA
GAGTGAGATGTAGTGAAGGAGAGGCCCCTGGCCCCTCTGACCGCCCATGAGAAGCGTCATTCATGGAAAGATCCTAG
GCTGAAATTAGAGATGTTTGGCCTCCCACCACCTTCCTGTTGGTTGAGAAATAAGCCAGTCTCCAGCCCTCTTGCTT
ATGGGCATTCCTCAGAAGAGACAAGGCCGCAGGCGGGAGGCCCCATAGGCCGGGGCTGACTTGCTCTCAGTGAACCT
CTGCTCTTTGTCAGCATAGGCCAGAGCCCGGATTGTCTGACCCACACCCAGCCCAGCCACGGCCTTCATGAAATGGG
AGCTTCCCCACATGCTTTGGGTCATTATCCAGATTCTTAACCAGAGTTCTCATGTTTCAGAGCCCTCAGAATGCCAT
AAAACTGTGTGTGGAAAAAAGCATGTGTACATTCATACATACATGTGTGTGCTTGTGCATGTGTGTGTGTGTACGTG
TGTGTGTGTACATGCGTTTTTCTGGAGAGACAGTCTTTAGCTTCAACAAATTCTTAAAAGGATTCCTGCCCCAAGAA
AAATCAAGAACCACCAGGTTTTTGGAAGTGCAGAGTGTGGTAAAGAACC
<210> SEQ ID NO 216
<211> Length: 132
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 216 >HSACMHCP_PEA_l_node_48
GTACCAGCACAGCGCCCCTTCAGCAGGCCAGCGCTACTGGCTCCAGATTCCTTTTCCTGTCAGGGTATGGGACTGTG GAAGCCTGGGAGTGTGCTCAGTGATTCTCTCTTTGCCTCTTCACCCTGCCCTCAG
<210> SEQ ID NO 217
<211> Length: 310
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 217
>HSACMHCP_PEA_l_node_49
CCCATGGGCATCATGTCCATCCTGGAGGAGGAGTGCATGTTCCCCAAGGCCACTGACATGACCTTCAAGGCCAAGCT 611 GTACGACAACCACCTGGGCAAGTCCAACAATTTCCAGAAGCCACGCAACATCAAGGGGAAGCAGGAAGCCCACTTCT
CCCTGATCCACTACGCCGGCACTGTGGACTACAACATCCTGGGCTGGCTGGAAAAAAACAAGGATCCTCTCAACGAG
ACTGTTGTGGCCCTGTACCAGAAGTCCTCCCTCAAGCTCATGGCCACTCTCTTCTCCTCCTACGCAACTGCCGATAC
TG
<210> SEQ ID NO 218
<211> Length: 124
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 218
>HSACMHCP_PEA_l_node_57
GTATCGCATCCTGAACCCAGTGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGACAGAGAAGCTGCTCA
GCTCTCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAG
<210> SEQ ID NO 219
<211> Length: 137
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 219
>HSACMHCP_PEA_l_node_59
GTGTTCTTCAAGGCAGGGCTGCTTGGGCTGCTGGAGGAGATGCGGGATGAGAGGCTGAGCCGCATCATCACGCGCAT
GCAGGCCCAAGCCCGGGGCCAGCTCATGCGCATTGAGTTCAAGAAGATAGTGGAACGCAG
<210> SEQ ID NO 220
<211> Length: 256
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 220
>HSACMHCP_PEA_l_node_61
GGATGCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATGGGGGTCAAGAATTGGCCCTGGATGAAGCTCTACT
TCAAGATCAAGCCGCTGCTGAAGAGCGCAGAGACGGAGAAGGAGATGGCCACCATGAAGGAAGAGTTCGGGCGCATC
AAAGAGACGCTGGAGAAGTCCGAGGCTCGCCGCAAGGAGCTGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAA
TGACCTGCAGCTCCAAGTGCAGGCG
<210> SEQ ID NO 221 612 <211> Length: 243
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 221
>HSACMHCP_PEA_l_node_63
GAACAAGACAACCTCAATGATGCTGAGGAGCGCTGCGACCAGCTGATCAAAAACAAGATTCAGCTGGAGGCCAAAGT
AAAGGAGATGAATGAGAGGCTGGAGGATGAGGAGGAGATGAACGCGGAGCTCACTGCCAAGAAGCGCAAGCTGGAAG
ACGAGTGCTCAGAGCTCAAGAAGGACATTGATGACCTGGAGCTGACACTGGCCAAGGTGGAGAAGGAGAAGCATGCA
ACAGAGAACAAG
<210> SEQ ID NO 222
<211> Length: 177
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 222
>HSACMHCP_PEA_l_node__65
GTGAAGAACCTAACAGAGGAGATGGCTGGGCTGGATGAAATCATCGCTAAGCTGACCAAGGAGAAGAAAGCTCTACA
AGAGGCCCATCAGCAGGCCCTGGATGACCTTCAGGTTGAGGAAGACAAGGTCAACAGCCTGTCCAAGTCTAAGGTCA
AGCTGGAGCAGCAGGTGGATGAT
<210> SEQ ID NO 223
<211> Length: 146
<212> Type: DNA
<213> ORGANISM: Homo sapiens
>HSACMHCP_PEA_l_node_67
CTGGAGGGATCCCTAGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGCGAGCAAAGCGGAAACTGGAGGGCGACCT
GAAGCTGACCCAGGAGAGCATCATGGACCTGGAAAATGATAAACTGCAGCTGGAAGAAAAGCTTAAGAA
<210> SEQ ID NO 224
<211> Length: 270
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 224
>HSACMHCP_PEA_l_node_71
GCACGCATCGAGGAGCTGGAGGAGGAGCTGGAGGCCGAGCGCACCGCCAGGGCTAAGGTGGAGAAGCTGCGCTCAGA 613 CCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCCGGCGGGGCCACGTCCGTGCAGATCGAGATGA
ACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCACGCTGCAGCACGAGGCCACTGCC
GCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAG
<210> SEQ ID NO 225
<211> Length: 337
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 225
>HSACMHCP_PEA_l_node_81
GTGAGGCCCAGTGGGGAGGGTGGGCAGGCTTGATGGCAGCCCTGGGGCAATTCATCTCAGTGCCAGAAATGGAGCCT
GGAGCTGGAAAGAGTCCTCTGCAAGGGAAAGACCCTCCAGTCTAGGTTCTGCCCTGCAGCTAAGCGTCATTTAATGC
CTCTTTTCTTATTCGTAAGGGGATGGGGTGAGCAGACTGGGAAACTCCTCAAACAGTGAGGTGCCACATCAGCCCAC
ATGGTGAATAAGGCTGGGCTTGGTTGAAGTACTACATAAGAAGAGAATCTAGAGAATGGGGCACAGGGAGTCCCTCC
CACCTCCTGGTGCCCCCCCCCCTCCCCAG
<210> SEQ ID NO 226
<211> Length: 184
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 226
>HSACMHCP_PEA_l_node_87
AAAGAAGCTGGCCCAGCGGCTGCAGGATGCCGAGGAGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCACTGGAGA
AGACCAAGCACCGGCTACAGAATGAGATAGAGGACTTGATGGTGGACGTAGAGCGCTCCAATGCTGCTGCTGCAGCC
CTGGACAAGAAGCAGAGAAACTTTGACAAG
<210> SEQ ID NO 227
<211> Length: 189
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 227
>HSACMHCP_PEA_l_node_89
ATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCTGAGCTGGAGTCCTCACAGAAGGAGGCTCGCTCCCT
CAGCACAGAGCTCTTCAAGCTCAAGAACGCCTACGAGGAGTCCCTGGAGCACCTAGAGACCTTCAAGCGGGAGAACA
AGAACCTTCAGG 614
<210> SEQ ID NO 228
<211> Length: 135
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 228
>HSACMHCP_PEA_l_node_96
GAGGAGGGCAAGATCCTCCGGGCCCAGCTAGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAGAGAA
GGACGAGGAGATGGAACAGGCCAAGCGCAACCACCAGCGGGTGGTGGACTCGCTGCAG
<210> SEQ ID NO 229
<211> Length: 129
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 229
>HSACMHCP_PEA_l_node_97
ACCTCCCTGGATGCAGAGACACGCAGCCGCAACGAGGTCCTGAGGGTGAAGAAGAAGATGGAAGGAGACCTCAATGA
GATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCGCCGAGGCCCAGAAG
<210> SEQ ID NO 230
<211> Length: 204
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 230
>HSACMHCP_PEA_l_node_100
GACACCCAGATCCAGCTGGACGATGCGGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCG
CAACAACCTGCTGCAGGCTGAGCTGGAGGAGCTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGG
AGCAGGAGCTGATTGAGACCAGCGAGCGGGTGCAGCTGCTGCATTCCCAG
<210> SEQ ID NO 231
<211> Length: 198
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 231 615 >HSACMHCP_PEA_l_node_105
GTAAGTGACCGCCCACCTTCCGCCTCCCCTAAAGACAGAAACAAGGCCTTGGGTCCAGGCCAGGCCACTGTGCTGTA
ACACCAAGCCAACTCTGCAGTTCTGTGGATTTGAGGGCCTGATGGGAGAAAGGAGATCCTTGGGGGGCAAAAGGCCC
CGGCCCCTGGCCCATGTTCCTTGCCACCTCTCTCCTGCACACAG
<210> SEQ ID NO 232
<211> Length: 276
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 232
>HSACMHCP_PEA_l_node_106
GCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAACATGGA
GCAGACCATTAAGGACCTGCAGCACCGGCTGGACGAGGCCGAGCAGATCGCCCTCAAGGGAGGCAAGAAGCAGCTGC
AGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGGGTGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAG
GGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAG
<210> SEQ ID NO 233
<211> Length: 224
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 233
>HSACMHCP_PEA_l_node_l07
GTGCGGCGGACGCCAGACACCGGGAGTAGATGTGGAAGTTTCTTCTCTGGCCCCACTGCCCCGCCCTCACAGGGCTC
CTCTCACCTCCTCCTTGAGATGCTGTTGGTAGATTTAACGTTCTTCTCACGCTCTGCAGTCAGTTTGACTTGAGTCT
ATGAGTTTTTCCAGCAAATGAAGAATCTACTTCTACTTCCTGAAAACTCTTCTAACTAGTCTTTCCCCAG
<210> SEQ ID NO 234
<211> Length: 897
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 234
>HSACMHCP_PEA_l_node_108
GTTTCTTTCTTTCTTTTTTTTTTTTTTTAATAACTCTAAGTGCTACCATGAAGACTTCAGAACAGTTCAAAGAATCC
TTCCACCTTCGACTGTGGGGATAAGAGTCAGGGGAGGGGAAAAGACCCGGAAATCTTCCATAGAACTTCTGGCACAC
AAAGAGAAGGCCACAGAGAAAGAGGACCCTAGAATGCTCTAAAACCTCCACTTGCATAGCTGAGAGCTGTGCCCTTG 616
GCCCGTTATTTTCAGTGTACCTGGGAAGAAAAGGCCAAGGAGACGAGGGTGTCAGTCCATTTGATAGATGGATACCA
GAGGCACAAGAAAGAGGTTACAGATACAGAACCACAGAGTGATTTGTGGACAGAAGTAGAAATGGCATCCTGGCACA TACAATGATAAAGAGATAGGAATGATCGAGTGACGTTGGAGCCAGTGATCCCGATGCCTGAATTCTGGCCCAGTACA ATATATTAGAATGTAGAATAATCTGGATTATGATAATACCCCCTTCTTTCTGCATTCTTTTTCTGGTCAAGAACTAC TGGCCAAGAGAACCTATGTAAGTCCAGGTTGGAGCTTTATCCACCATACTGGAGCTGGAACAGACCTGGTGCTTTTA TATTACCACATTAGGGAATTCCATTAGGTTCTGAGCCCCTCCCCCTACTTCTAGCTTTATGACTTCAGCCTTCATTG CTCTGTGGATCCCTGACTGACAACCTTGCATTGCCCCTTTGACCTACGATAGAGTCAGAGAATCTTCCCCACCACCT CTTTGACCTGGATCATTGCAGGGAGGGGCAGCAAAGGCAAGGGGAGAAGAGTAAAATGATGGAGGAGGGAAAGGTGA TTGCATTTGCTCCCCCTCCAAACCAGCTTCTCCCACCCTCCCACCCCCAG
<210> SEQ ID NO 235
<211> Length: 135
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 235
>HSACMHCP_PEA_l_node_lll
GAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCATGAGCTGGATGAGGCAGAGGAGCGGGCGGA
CATCGCTGAGTCCCAGGTCAACAAGCTTCGAGCCAAGAGCCGTGACATTGGTGCCAAG
<210> SEQ ID NO 236
<211> Length: 1,927
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 236
>HSACMHCP_PEA_l_node_113
CAAAAAATGCACGATGAGGAGTGACACTGCCTCGGGAACCTCACTCTTGCCAACCTGTAATAAATATGAGTGCCAAA
CTCTGCCTGAGCCCATCTGTCCTTCCTGCCAGCTGTCCATCCTGGATCAGGGCAGTAGGGGGCCTGAGAGGAGGGAG
GCCCCCAGCCCCTGTATCAGAGCTGCCAGAGCCAAGGCATCCCATATCCACAAGGAAGGAGACCGAGGTGCAGAGGA
GTGAGGTGTTCTGCCTGACGTGGACAGCTGTGAGTCCCAGTTCTGCTCAGTCAACCACACAAGGGTGGAGAGGGAGA
AATTTCAAAAGTGAAGAAAACAATGGCATCAAAATGGTGAGCCAGTCCAAGATGCTACGAGATAGAATTTTGGTGCC
GAAGTTGAAGCCACTCTCCACCTACCCCACCCCTGAGGCTGCAATGATTAAAGGTGTCCTAGGACACCCATTCTTTC
TGAAATGAATTTTCCACCAATGCCAGAAAAGGCTCAGAGCTGGCTGAGAATTAAGGTATGGGAAAGGAGATGGGAGA
GATTCCATTCTAGTCAGCCCCTAGGAAGTAACTCCCAGGGAGCCCCCTCCCTGTCTTCCCCAGGGGTCTCCCCCTGC
CTCCTATGATTCAGCACCTCACCGTGAGGGCATCTTGAGACTCTGGGGCCAATCAACACTGAGCCCAAACCAATATG
CCATGAGGACCAAGCCTGGGCATTGCTCATTTCATGTTGGTTCTCACACAGACACAGATGGCACAGGTGCCTGTACA
GGGAAACACTGTGGTCACATTTCTGCTCTCTCTAAGCTCCTACTGGGGACAGTCTGGCCTGGATCACACAGCTGCTT 617 GTGGGACAGGCCCGGTCCTGACCCCGTTCTGCACAAAGCAAATCCCCACTCCCCACTGGGCTTTGCAGCCAGGCTCT
GCTGACCGCCTCCTTAACCGTTCACCTGGCACCCCATCTCCCTGACTCCCCAAGTGGAGCCTCTTCTATCCCTCCTC
TGAGACCATGAGAATGGACTGTGCATAAAGCCCTGAGAAATGTGAGCAGTGACCAGAGAAACACAAAATCCTGTTGG
TTCTAGCCCAGGAGAGGCTGCCAGTTCTGATGGTGAGCCAGGACACAAGGATAGGAGAACAGGAAGCAGGAGGCAGG
AAAAAGACCAAGAGAGAGGAGTGGCTGCCACCAAGGAAGCAGAGCGCTCTGACCAGAGTTCAAGATCCAGGGTTCGG
GCAGGACTTGGGAGCTGGGGCCTGCAGCTGGAAGGAGCGCTCCAGAAGAAGGATTGTATCTCAGGGCGGGAACACAC
ACACATCAGCGACAGGAGATAGCACGTCAGCTGGGATGGAGCTGCTGAGCCAGGCCATGCTGGGCTCCTCGGGCTGG
GCAGGAACGTCTGGCTGCACATCTGTCTGTCTCGGCCCAGCAGGGCTGACTCCCGGGCTGTGGCAGTGTCTGCTCCA
AACTCCCCTGGGCCTTCCCATAGCATTCACTGTGGGGAGCTCTTGACCAGCTTGTCTCTTTCCCAGCCTGTGAGTGC
TAAAGGGCAGGCCCCCCGTCACCTCTGAGGCCCTGGCACCCAGCACAGTGTGCATGGGAGATGCTCAGGAAATGTGT
GCTGAGGAGCTGGCAAGCTGGGAGGGTGGACCCGCAGTGGAGGGAAGAGTTGGCCATTCTTTTCTGAGCTACAAGGA
GGCTCAGTACAGTATCCAGAACACTCGCTTAGGTGTCAGAAGAGCTGCGTTCTGGCCCTAGCTCTGTCACAAATGAG
TTCACCTCCCCTGGCTGGGCCTGTTTTCTCTTATGTGAAATGAGGGCATTGGACCAGCTGATAATCAACGGCTCTCC
CAGCATTCGCATTTTGGGAAATCTCTCCCTCCTCTGATACCTCAGGCTGCCCTCTCCCTGCCTCCTGTTCCTGTCAT
AG
<210> SEQ ID NO 237
<211> Length: 21
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 237
>HSACMHCP_PEA_l_node_0
CCTATCAGTACATGCTGACAG
<210> SEQ ID NO 238
<211> Length: 46
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 238
>HSACMHCP_PEA_l_node_3
CGAGTTCAAGCTGGAGCTGGATGACGTCACCTCCAACATGGAGCAG
<210> SEQ ID NO 239
<211> Length: 15
<212> Type: DNA
<213> ORGANISM: Homo sapiens 61 !
<400> sequence: 239
>HSACMHCP_PEA_l_node_4
ATCATCAAGGCCAAG
<210> SEQ ID NO 240
<211> Length: 31
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 240 >HSACMHCP_PEA_l_node_l 6 GAGGACAGATAGAGAGACTCCTGCGGCCCAG
<210> SEQ ID NO 241
<211> Length: 33
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 241 >HSACMHCP_PEA_l_node_l 8 ATTCTTCAGGATTCTCCGTGAAGGGATAACCAG
<210> SEQ ID NO 242
<211> Length: 22
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 242
>HSACMHCP_PEA_l_node_23
CTACGCGGCCTGGATGATATAT
<210> SEQ ID NO 243
<211> Length: 28
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 243
>HSACMHCP PEA 1 node 27 619
ATCGGGAGAACCAGTCCATCCTCATCAC
<210> SEQ ID NO 244
<211> Length: 112
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 244 >HSACMHCP_PEA_l_node_29
GGGAGAATCCGGGGCGGGGAAGACTGTGAACACCAAGCGTGTCATCCAGTACTTTGCCAGCATTGCAGCCATAGGTG ACCGTGGCAAGAAGGACAATGCCAATGCGAACAAG
<210> SEQ ID NO 245
<211> Length: 93
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 245
>HSACMHCP_PEA_l_node_31
GGCACCCTGGAGGACCAGATCATCCAGGCCAACCCCGCTCTGGAGGCCTTCGGCAATGCCAAGACTGTCCGGAACGA
CAACTCCTCCCGCTTT
<210> SEQ ID NO 246
<211> Length: 64
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 246
>HSACMHCP_PEA_l_node_33
GGGAAATTCATTAGGATCCACTTTGGGGCCACTGGAAAGCTGGCTTCTGCAGACATAGAGACCT
<210> SEQ ID NO 247
<211> Length: 99
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 247
>HSACMHCP_PEA_l_node_35
ACCTGCTGGAGAAGTCCCGGGTGATCTTCCAGCTGAAAGCTGAGAGAAACTACCACATCTTCTACCAGATTCTGTCC 620 AACAAGAAGCCGGAGTTGCTGG
<210> SEQ ID NO 248
<211> Length: 104
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 248
>HSACMHCP_PEA_l_node_37
ACATGCTGCTGGTCACCAACAATCCCTACGACTACGCCTTCGTGTCTCAGGGAGAGGTGTCCGTGGCCTCCATTGAT
GACTCCGAGGAGCTCATGGCCACCGAT
<210> SEQ ID NO 249
<211> Length: 117
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 249
>HSACMHCP_PEA_l_node_39
AGTGCCTTTGACGTGCTGGGCTTCACTTCAGAGGAGAAAGCTGGCGTCTACAAGCTGACGGGAGCCATCATGCACTA
CGGGAACATGAAGTTCAAGCAGAAGCAGCGGGAGGAGCAG
<210> SEQ ID NO 250
<211> Length: 22
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 250 >HSACMHCP_PEA_l_node_40 GCGGAGCCAGACGGCACCGAAG
<210> SEQ ID NO 251
<211> Length: 71
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 251 >HSACMHCP PEA 1 node 51 621 GGGACAGTGGTAAAAGCAAAGGAGGCAAGAAAAAGGGCTCATCCTTCCAGACGGTGTCGGCTCTCCACCGG
<210> SEQ ID NO 252
<211> Length: 88
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 252
>HSACMHCP_PEA_l_node_53
GAAAATCTCAACAAGCTAATGACCAACCTGAGGACCACCCATCCTCACTTTGTGCGTTGCATCATCCCCAATGAGCG
GAAGGCTCCAG
<210> SEQ ID NO 253
<211> Length: 118
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 253
>HSACMHCP_PEA_l_node_55
GGGTGATGGACAACCCCCTGGTCATGCACCAGCTGCGCTGCAATGGCGTGCTGGAGGGCATCCGCATCTGCAGGAAG
GGCTTCCCCAACCGCATCCTCTACGGGGACTTCCGGCAGAG
<210> SEQ ID NO 254
<211> Length: 91
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 254
>HSACMHCP_PEA_l_node_69
GAAGGAGTTTGACATTAATCAGCAGAACAGTAAGATTGAGGATGAGCAGGCGCTGGCCCTTCAACTACAGAAGAAAC
TGAAGGAAAACCAG
<210> SEQ ID NO 255
<211> Length: 12
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 255 >HSACMHCP PEA 1 node 72 622 CTGGGCGAGCAG
<210> SEQ ID NO 256
<211> Length: 30
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 256 >HSACMHCP_PEA_l_node_73 ATCGACAACCTGCAGCGGGTGAAGCAGAAG
<210> SEQ ID NO 257
<211> Length: 78
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 257 >HSACMHCP_PEA_l_node_74
CTGGAGAAGGAGAAGAGCGAGTTCAAGCTGGAGCTGGATGACGTCACCTCCAACATGGAGCAGATCATCAAGGCCAA G
<210> SEQ ID NO 258
<211> Length: 102
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 258 >HSACMHCP_PEA_l_node_77
GCAAACCTGGAGAAAGTGTCTCGGACGCTGGAGGACCAGGCCAATGAGTACCGCGTGAAGCTAGAAGAGGCCCAACG CTCCCTCAATGATTTCACCACCCAG
<210> SEQ ID NO 259
<211> Length: 25
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 259 >HSACMHCP PEA 1 node 78 623 CGAGCCAAGCTGCAGACCGAGAATG
<210> SEQ ID NO 260
<211> Length: 119
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 260
>HSACMHCP_PEA_l_node_80
GAGAGTTGGCCCGGCAGCTAGAGGAAAAGGAGGCGCTAATCTCGCAGCTGACCCGGGGGAAGCTCTCTTATACCCAG
CAAATGGAGGACCTCAAAAGGCAGCTGGAGGAGGAGGGCAAG
<210> SEQ ID NO 261
<211> Length: 24
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 261
>HSACMHCP_PEA_l_node_82
GCGAAGAACGCCCTGGCCCATGCA
<210> SEQ ID NO 262
<211> Length: 66
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 262
>HSACMHCP_PEA_l_node_83
CTGCAGTCGGCCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACAGAGGCCAAG
<210> SEQ ID NO 263
<211> Length: 72
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 263
>HSACMHCP_PEA_l_node_8
GCCGAGCTGCAGCGCGTCCTGTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGAC 624
<210> SEQ ID NO 264
<211> Length: 35
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 264
>HSACMHCP_PEA_l_node_85
GCCATTCAGCGGACTGAGGAGCTCGAAGAGGCCAA
<210> SEQ ID NO 265
<211> Length: 104
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 265
>HSACMHCP_PEA_l__node_90
GTGTGCTGGGGGTCCAAGAGGCCAGAGATGAGTTGGTGGGAGGGAGGGCCATGCAGGGGCAGGGGGAACATAGGCTT
TGAGCTTTCTGGCCCTCTGGTCCCCAG
<210> SEQ ID NO 266
<211> Length: 77
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 266
>HSACMHCP_PEA_l_node_91
AGGAAATCTCGGACCTTACTGAGCAGCTAGGAGAAGGAGGAAAGAATGTGCATGAGCTGGAGAAGGTCCGCAAACAG
<210> SEQ ID NO 267
<211> Length: 21
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 267
>HSACMHCP_PEA_l_node_92
CTGGAGGTGGAGAAGCTGGAG 625 <210> SEQ ID NO 268
<211> Length: 27
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 268
>HSACMHCP_PEA_l_node_93
CTGCAGTCAGCCCTGGAGGAGGCAGAG
<210> SEQ ID NO 269
<211> Length: 15
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 269
>HSACMHCP_PEA_l_node_95
GCCTCCCTGGAGCAC
<210> SEQ ID NO 270
<211> Length: 30
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 270
>HSACMHCP_PEA_l_node_98
CAAGTCAAGAGCCTCCAGAGCTTGCTGAAG
<210> SEQ ID NO 271
<211> Length: 57
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 271
>HSACMHCP_PEA_l_node_103
AACACCAGCCTCATCAACCAGAAGAAGAAGATGGAGTCGGATCTGACCCAGCTCCAG
<210> SEQ ID NO 272 <211> Length: 69 626 <212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 272
>HSACMHCP_PEA_l_node_104
TCGGAAGTGGAGGAGGCAGTGCAGGAGTGCAGAAACGCCGAGGAGAAGGCCAAGAAGGCCATCACGGAT
<210> SEQ ID NO 273
<211> Length: 96
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 273
>HSACMHCP_PEA_l_node_109
ACAGAGGAAGACAAAAAGAACCTGCTGCGGCTACAGGACCTGGTGGACAAGCTGCAACTGAAGGTCAAGGCCTACAA
GCGCCAGGCCGAGGAGGCG
<210> SEQ ID NO 274
<211> Length: 20
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 274>S67314 segl5R Reverse primer
GCCAACTCTCAGCTCCTCCC
<210> SEQ ID NO 275
<211> Length: 101
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 275>S67314 segl5 Amplicon
TTCCTTGGCATCTCCAATGGAGTAGAGAGAAGGCAACAAAGCTTCTCAGACCCACATTACCGAGCTATAACAACCAT
GGCTGGGAGGAGCTGAGAGTTGGC<210> SEQ ID NO 276
<211> Length: 21
<212> Type: DNA
<213> ORGANISM: Homo sapiens 627 <400> sequence: 276>Forward primer S67314seg4F
CCAAGCCTACCACAATCATCG
<210> SEQ ID NO 277
<211> Length: 21
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 277>Reverse primer S67314seg4R
CTCCACCCCCAACTTAAAGCT
<210> SEQ ID NO 278
<211> Length: 101
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 278>Amplιcon S67314seg4:
CCAAGCCTACCACAATCATCGAAAAGAATGGGGACATTCTCACCCTAAAAACACACAGCACCTTCAAGAACACAGAG
ATCAGCTTTAAGTTGGGGGTGGAG<210> SEQ ID NO 279
<211> Length: 22
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 279>N56180 seg6F
ATATCCCAGTGGTGGTTGCATT
<210> SEQ ID NO 280
<211> Length: 17
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 280>N56180 seg6R CCCTCCCCAGCGTTTCC
<210> SEQ ID NO 281
<211> Length: 215
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 281 628 >S67314_PEA_1_P4
MVDAFLGT KLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTAD
DRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLILVRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTR
EWLWVRVVSGGNFLCSGFGLTQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL
<210> SEQ ID NO 282
<211> Length: 178
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 282
>S67314_PEA_1_P5
MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTAD
DRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLILDVLTA PSIYRRQVKVLREDEITILPWHLQWSREKATK
LLRPTLPSYNNHGWEELRVGKSIV
<210> SEQ ID NO 283
<211> Length: 126
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 283
>S67314_PEA_1_P6
MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTAD
DRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLILMEKLQLRNVK
<210> SEQ ID NO 284
<211> Length: 144
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 284
>S67314_PEA_1_P7
MVDAFLGTWKLVDSKNFDDYMKSLAHILITFPLPSGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFK
LGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA
<210> SEQ ID NO 285 <211> Length: 240 629 <212 > Type : PRT
<213> ORGANISM : Homo sapiens
<400> sequence : 285
>N56180_P2
MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEIVL
ELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLE
VQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFDKGVLWLTPVIPTLWEADGGGLHEPWSWRPAW
ATWLQRNYL
<210> SEQ ID NO 286
<211> Length: 446
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 286
>N56180_P4
MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEIVL
EHWQISQWWLHFQTPREEGKMKLLELSESADGAAWKRWGGNSNTHRIQLVAQVLEHKAIGFVMVDAKKEAKLAKKLG
FDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEE
AAEHFQPYIKFFATFDKGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFET
EDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTD
ADSVWMEIPDDDDLPTAEELEDWIEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE
<210> SEQ ID NO 287
<211> Length: 337
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 287
>N56180_P5
MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEIVL
ELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDVAKKLSLKMNEVDF
YEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFETWEDDLNGIHIVAFAEKSDPDGYEFLEILKQVAR
DNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKI
NTEDDDEDDDDDDNSDEEDNDDSDDDDDE
<210> SEQ ID NO 288 630
<211> Length: 321
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 288
>N56180_P6
NETEAEQSYVRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEIVLELVAQVL
EHKAIGFVMVDAKKEAKLAKKLDYKAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEVDFYEPFMDEPIAIPNKPY
TEEELVEFVKEHQRPTLRRLRPEEMFETWEDDLNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWIDPD
DFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKINTEDDDEDDDDDDNSD
EEDNDDSDDDDDE
<210> SEQ ID NO 289
<211> Length: 212
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 289
>N56180_P7
MSSWLSAGSPSSLSVVAKKLSLKMNEVDFYEPFMDEPIAIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFETWEDD
LNGIHIVAFAEKSDPDGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADS
VWMEIPDDDDLPTAEELEDWIEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE
<210> SEQ ID NO 290
<211> Length: 133
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 290
>N56180_P8
MCRGYSTLLNPVSDGYEFLEILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVW
MEIPDDDDLPTAEELED IEDVLSGKINTEDDDEDDDDDDNSDEEDNDDSDDDDDE
<210> SEQ ID NO 291
<211> Length: 252
<212> Type: PRT
<213> ORGANISM: Homo sapiens 631 < 400> sequence : 291
>N56180_P9
MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQLKEIVL
ELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLE
VQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEVDFYEPFMDEPIAIPNKP
YTEEELVEFVKEHQRSRNWTQ
<210> SEQ ID NO 292
<211> Length: 451
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 292
>T10377_P2
MEISLVKCSEANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGW
STSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQSSALDRFNAMNSALAS
DSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMREMTKKLY
SQYEEKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIGELDRLIERMEKERHQLQLQLLEH
ETEMSGELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKISFLEG
ENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNYTPYTRVLELTMKKTLT
<210> SEQ ID NO 293
<211> Length: 438
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 293
>T10377_P5
MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGWYGVVR
RSDQNQQKEMWYGWSTSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQS
SALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQ
EANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIGELDRLIER
MEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEENNELQSRLDYLT
ETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNYTPYTRVLELTMKKTLT
<210> SEQ ID NO 294 <211> Length: 407 <212> Type: PRT 632
<213> ORGANISM: Homo sapiens
<400> sequence: 294
>T10377_P6
MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGVVR
RSDQNQQKEMVVYGWSTSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQS
SALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQ
EANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIGELDRLIER
MEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQ
LLILQLLEKISFLEGEPNRQDS
<210> SEQ ID NO 295
<211> Length: 390
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 295
>T10377_P7
MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGVVR
RSDQNQQKEMVVYGWSTSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQS
SALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQ
EANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIGELDRLIER
MEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIMSHELFSRFSL
RLFGR
<210> SEQ ID NO 296
<211> Length: 466
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 296
>T10377_P8
MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSNGEPTRKLPQGVVYGVVR
RSDQNQQKEMVVYGWSTSQLKEEMNYIKDVRATLEKVRKRMYGDYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQS
SALDRFNAMNSALASDSIGLQKTLVDVTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQ
EANAEVMREMTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFLKAIEEANKKMQAAEISLEEKDQRIGELDRLIER
MEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLRERIRHLDDMVHCQQKKVKQMVEEIESLKKKLQQKQ
LLILQLLEKISFLEGENNELQSRLDYLTETQAKTEVETREIGVGCDLLPSQTGRTREIVMPSRNYTPYTRVLELTMK 633 KTLT
<210> SEQ ID NO 297
<211> Length: 145
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 297
>Z24874_PEA_2_P5
MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLESLDMEAMLDTVQAWLSSPQ
KFARAHGVSVQPEASDTHILLLEGFLLYSYKPLVDLYSRRYFLTVPYEECK RRSLPGRHEVPRGALP
<210> SEQ ID NO 298
<211> Length: 121
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 298
>Z24874_PEA_2_P6
MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLESLDMEAMLDTVQAWLSSPQ
KFARAHGVSVQPEASDTHILLLEGFLLYSYNLPGRHEVPRGALP
<210> SEQ ID NO 299
<211> Length: 101
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 299
>HUMCDDANF_P2
MPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRGP DSSDRSALLKSKLRALLTAPRSLRR
SSCFGGRMDRIGAQSGLGCNSFRY
<210> SEQ ID NO 300
<211> Length: 118
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 300 634 >HUMCDDANF_P3
MSSFSTTTNLLDHLEEKMPLEDEVVPPQVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRGPWDSSDRSAL
LKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY
<210> SEQ ID NO 301
<211> Length: 137
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 301
>HUMTROPIA_PEA_2_P5
MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQELEREAEERRGEKGRALS
TRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTKNITEVGRMGSSGTFGVG
<210> SEQ ID NO 302
<211> Length: 182
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 302
>HUMTROPIA_PEA_2_P12
MADGSSDAKKSKISASRKLQLKTLLLQIAKQELEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLHARVD
KVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTLRRVRISADAMMQALLGARAKESLDLRAHLKQVKKEDTE
KENREVGDWRKNIDALSGMEGRKKKFES
<210> SEQ ID NO 303
<211> Length: 85
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 303 >HUMTROPIA_PEA_2_Pl 7
MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKVGRGFLGAEYRRRRDPRPWEWGEEPGLRRGRGLRGGASGAE FCRGSCSDW
<210> SEQ ID NO 304 <211> Length: 13 <212> Type: PRT 635
<213> ORGANISM: Homo sapiens
<400> sequence: 304 >HUMTROPIA_PEA_2_P18 MADGSSDAVRAAG
<210> SEQ ID NO 305
<211> Length: 387
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 305
>HUMSMCK_P4
MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRKHNNCMAECLTPAIYAKLR
NKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQ
FDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKP
VSPLLTCAGMARDWPDARGIWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQERGWEFMWN
ERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSKILENLRLQKRGTGGVDTAAVADVYDISNIDRIGRSEVTSLS
LS
<210> SEQ ID NO 306
<211> Length: 346
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 306
>HUMSMCK_P5
MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRKHNNCMAECLTPAIYAKLR
NKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQ
FDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKP
VSPLLTCAGMARDWPDARGI HNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQERGWEFMWN
ERLGYILTCPSNLGTGLRAGVHVRIPKLSKVLLCAQWP
<210> SEQ ID NO 307
<211> Length: 224
<212> Type: PRT
<213> ORGANISM: Homo sapiens 636 <400> sequence: 307
>HUMSMCK_P6
MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRKHNNCMAECLTPAIYAKLR
NKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQ
FDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDA
<210> SEQ ID NO 308
<211> Length: 304
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 308
>HUMSMCK_P8
MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRKHNNCMAECLTPAIYAKLR
NKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQ
FDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKP
VSPLLTCAGMARDWPDARGIWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFERFCRGLKEVRCYLRFLDIY
<210> SEQ ID NO 309
<211> Length: 708
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 309
>H88495_PEA_3_P15
MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLSEEASAELRHHLHSPRDHPDENKDVSTE
NGHHFWSHPDREKEDEDVAKEYGHLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPS
HRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGH
HHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDD
DVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV
QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMS
HHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEED
KEEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQ
EYGNYQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQVRPHLTLKAPLGLRMHRDPLRTPSPKSWPLTQPLTP
DATLTPQAILTPTLT
<210> SEQ ID NO 310 <211> Length: 685 637 <212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 310
>H88495_PEA_3_P16
MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLSEEASAELRHHLHSPRDHPDENKDVSTE
NGHHFWSHPDREKEDEDVAKEYGHLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPS
HRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGH
HHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDD
DVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV
QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMS
HHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEED
KEEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQ
EYGNYQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQHCQFCYLCPLVCETVCAPGEHGRGPGKT
<210> SEQ ID NO 311
<211> Length: 696
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 311
>H88495_PEA_3_P17
MGHHRPWLHASVL AGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLSEEASAELRHHLHSPRDHPDENKDVSTE
NGHHFWSHPDREKEDEDVAKEYGHLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPS
HRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGH
HHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDD
DVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV
QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMS
HHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEED
KEEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQ
EYGNYQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQGPGRHAGNAGTLTQSLDCDAGVPPPAFQPLSTSYIY
FSE
<210> SEQ ID NO 312
<211> Length: 613
<212> Type: PRT
<213> ORGANISM: Homo sapiens 638 <400> sequence: 312
>H88495_PEA_3_P18
MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNNTGVAGLSEEASAELRHHLHSPRDHPDENKDVSTE
NGHHFWSHPDREKEDEDVAKEYGHLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPS
HRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGH
HHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDD
DVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV
QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMS
HHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEED
KEEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTAMH
<210> SEQ ID NO 313
<211> Length: 283
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 313
>Z36249_PEA_3_P2
MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGEQQWKSEKQREAELKKKKLEQ
RSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIIYKRTALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAI
HWASRGGNLDVLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDREGDTPLHDAVRLNRYKM
IRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTKAIFDSLRENSYKTSRIATF
<210> SEQ ID NO 314
<211> Length: 197
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 314
>Z36249_PEA_3_P3
MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGEQQWKSEKQREAELKKKKLEQ
RSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDEYKR
TALHRACLEGHLAIVEKLMEAGAQIEFRDMVNIFLCLGMSQKK
<210> SEQ ID NO 315 <211> Length: 177 <212> Type: PRT 63 9
<2 1 3> ORGANI SM : Homo sapiens
<400> sequence : 315
>Z3624 9_PEA_3_P4
MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGEQQWKSEKQREAELKKKKLEQ
RSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDEVRL
MQSTAKSSSLILCFLCFTPVLLI
<210> SEQ ID NO 316
<211> Length: 286
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 316
>Z36249_PEA_3_P5
MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGEQQWKSEKQREAELKKKKLEQ
RSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDELES
TAIHWASRGGNLDVLKLLLNKGAKISARDKLLSTALHVAVRTGHYECAEHLIACEADLNAKDREGDTPLHDAVRLNR
YKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTKAIFDSLRENSYKTSRIATF
<210> SEQ ID NO 317
<211> Length: 158
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 317
>Z25377_PEA_1_P12
MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRCWFNGIVEENDSNIWKFWY
TNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYI
AAGI
<210> SEQ ID NO 318
<211> Length: 166
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 318 >Z25377 PEA 1 P13 640 MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRCWFNGIVEENDSNIWKFWY
TNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYI
AAVSVGQECGSG
<210> SEQ ID NO 319
<211> Length: 210
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 319
>Z25377_PEA_1_P14
MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRCWFNGIVEENDSNIWKFWY
TNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYI
AADGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY
<210> SEQ ID NO 320
<211> Length: 114
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 320 >Z25377_PEA_1_P15
MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAADGISSLCYSSLSKSLLS QPLRETSSAINDISLLQALMPLLGWTSHWTCITVGLY
<210> SEQ ID NO 321
<211> Length: 87
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 321
>Z25377_PEA_1_P17
MRGEHNSTSYDSAVSILFSLVVMLYVI VQAVADMESYRNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAGLLFL
VVGRHIQIHH
<210> SEQ ID NO 322 <211> Length: 62 <212> Type: PRT 641
<213> ORGANISM: Homo sapiens
<400> sequence: 322
>Z25377_PEA_1_P18
MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGI
<210> SEQ ID NO 323
<211> Length: 45
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 323
>Z25377_PEA__1_P19
MKGSSGGVGLMGLWKRMTPIFGSSGTPISHRPRTAHMLTCLRTPS
<210> SEQ ID NO 324
<211> Length: 70
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 324
>Z25377_PEA_1_P20
MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAVSVGQECGSG
<210> SEQ ID NO 325
<211> Length: 68
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 325
>Z25377_PEA_1_P21
MRGEHNSTSYDSAVNGISSLCYSSLSKSLLSQPLRETSSAINDISLLQALMPLLGWTSH TCITVGLY
<210> SEQ ID NO 326
<211> Length: 1,904
<212> Type: PRT
<213> ORGANISM: Homo sapiens 642 <400> sequence: 326
>HSACMHCP_PEA_1_P2
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA
GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTE
ELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYE
ESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKL
ELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVK
KKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVV
EQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEEL
KKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERR
IKELTYQVRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT
<210> SEQ ID NO 327
<211> Length: 1,336
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 327
>HSACMHCP_PEA_1_P3
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF 643 GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA
GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKVRPSGEGGQA
<210> SEQ ID NO 328
<211> Length: 1,534
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 328
>HSACMHCP_PEA_1_P4
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFN MVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA 644 GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTE
ELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYE
ESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQGVLGVQEARDELVGGRAMQGQGEHRL
<210> SEQ ID NO 329
<211> Length: 1,788
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 329
>HSACMHCP_PEA_1_P6
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA
GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTE
ELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYE
ESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKL
ELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRWDSLQTSLDAETRSRNEVLRVK
KKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVV
EQTERSRKLAEQELIETSERVQLLHSQNTΞLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDVSDRPPSA
SPKDRNKALGPGQATVL 645 <210> SEQ ID NO 330
<211> Length: 1,434
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 330
>HSACMHCP_PEA_1_P12
MGLWKPGSVLSDSLFASSPCPQPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIH
YAGTVDYNILGWLEKNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNK
LMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQ
FIDSRKGTEKLLΞSLDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDAL
LVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQ
LQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVE
KEKHATENKVKNLTEEMAGLDEIIAKLTKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEK
KVRMDLERAKRKLEGDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELE
EELEAERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKH
ADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDF
TTQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEE
TEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIED
LMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKN
LQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDE
EMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLD
DAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLT
QLQSEVEEAVQECRNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQL
QKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQA
NTNLSKFRKVQHELDEAEERADIAESQVNKLRAKSRDIGAKQKMHDEE
<210> SEQ ID NO 331
<211> Length: 555
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 331
>HSACMHCP_PEA_1_P16
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAA MIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP 646 YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKVPPWPHHLCPLL
CHPDKVVAESLLHPRN
<210> SEQ ID NO 332
<211> Length: 1,847
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 332
>HSACMHCP_PEA_1_P25
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSIΞDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDPMGIMSILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLE
KNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVR
CIIPNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS
LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVK
NWPWMKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAE
ERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLT
EEMAGLDEIIAKLTKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLE
GDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVE
KLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNL
QRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGEL
ARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKA
NSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAA
LDKKQRNFDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGE
GGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVD
SLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIA
IVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECR
NAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGEL
EAEQKRNAESVKGMRKSERRIKELTYQVRRTPDTGSRCGSFFSGPTAPPSQGSSHLLLEMLLVDLTFFSRSAVSLT
<210> SEQ ID NO 333 647 <211> Length: 1,775
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 333
>HSACMHCP_PEA_1_P28
MLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAFGNAKTVRNDN
SSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFY
QILSNKKPELLDMLLVTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKF
KQKQREEQAEPDGTEDADKSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVT
RINATLETKQPRQYFIGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQ
ACIDLIEKPMGIMΞILEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILG LE
KNKDPLNETVVALYQKSSLKLMATLFSSYATADTGDSGKSKGGKKKGSΞFQTVSALHRENLNKLMTNLRTTHPHFVR
CIIPNERKAPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSS
LDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVK
NWP MKLYFKIKPLLKSAETEKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAE
ERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLT
EEMAGLDEIIAKLTKEKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLE
GDLKLTQESIMDLENDKLQLEEKLKKKEFDINQQNΞKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVE
KLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNL
QRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGEL
ARQLEEKEALISQLTRGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKA
NSEVAQWRTKYETDAIQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAA
LDKKQRNFDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGE
GGKNVHELEKVRKQLEVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVD
SLQTSLDAETRSRNEVLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIA
IVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECR
NAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGEL
EAEQKRNAESVKGMRKSERRIKELTYQTEEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHEL
DEAEERADIAESQVNKLRAKSRDIGAKQKMHDEE
<210> SEQ ID NO 334
<211> Length: 775
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 334 >HSACMHCP PEA 1 P29 648 MNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQII
KAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLSYTQQMEDLK
RQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKKL
AQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYEESQSELESS
QKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKLELQSALEEA
EASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVKKKMEGDLNE
MEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKL
AEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEELKKEQDTSAH
LERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERRIKELTYQTE
EDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKLRAKSRDIGAKQK
MHDEE
<210> SEQ ID NO 335
<211> Length: 108
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 335>N56180 seg6
ATATCCCAGTGGTGGTTGCATTTCCAAACCCCAAGAGAGGAAGGCAAAATGAAGTTGCTGGAGTTGAGTGAATCTGC
AGATGGAGCTGCGTGGAAACGCTGGGGAGGG<210> SEQ ID NO 336
<211> Length: 26
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 336>N56180 seg F
TTGATACCACTTAGTGTAGCTCCAGC
<210> SEQ ID NO 337
<211> Length: 23
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 337>N56180 seg R TCAAGTAGTTGCTACAGACGCCA
<210> SEQ ID NO 338
<211> Length: 1,939
<212> Type: PRT
<213> ORGANISM: Homo sapiens 649
<400> sequence: 338
>MYH6_HUMAN_V1
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFΞLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA
GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTE
ELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYE
ESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKL
ELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVK
KKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVV
EQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEEL
KKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERR
IKELTYQTEEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKLRAK
SRDIGAKQKMHDEE
<210> SEQ ID NO 339
<211> Length: 1,939
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 339 >MYH6 HUMAN V2 650 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIEDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA
GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTE
ELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYE
ESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKL
ELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVK
KKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVV
EQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMEADLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEEL
KKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERR
IKELTYQTEEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKLRAK
SRDIGAKQKMHDEE
<210> SEQ ID NO 340
<211> Length: 1,939
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 340 >MYH6_HUMAN_V3 MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVK EDQVLQQNPPKFDKIQDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSE APPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANP 651 ALEAFGNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLL
VTNNPYDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTE
DADKSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYF
IGVLDIAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSI
LEEECMFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQ
KSSLKLMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDN
PLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKV
FFKAGLLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLL
KSAETEKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEA
KVKEMNERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTK
EKKALQEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLEN
DKLQLEEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISE
RLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFK
LELDDVTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLT
RGKLSYTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDA
IQRTEELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEW
KQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQL
EVEKLELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNE
VLRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEE
LRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMESDLTQLQSEVEEAVQECRNAEEKAKKAITDAAM
MAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMR
KSERRIKELTYQTEEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVN
KLRAKSRDIGAKQKMHDEE
<210> SEQ ID NO 341
<211> Length: 229
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 341
>BAC85244
MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRCWFNGIVEENDSNIWKFWY
TNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIAΞFLIICAAPFASHFLYKAGGGSYI
AAGILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAGLLFLVVGRHIQIHH
<210> SEQ ID NO 342 <211> Length: 133 <212> Type: PRT 652 <213> ORGANISM: Homo sapiens
<400> sequence: 342
>Q96NR4
MRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGILFSLVVMLYVIWVQA
VADMESYRNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAGLLFLVVGRHIQIHH
<210> SEQ ID NO 343
<211> Length: 110
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 343
>Q8 W45
MLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVL
YGWSFFLAPAGIFFSLLAGLLFLVVGRHIQIHH
<210> SEQ ID NO 344
<211> Length: 319
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 344
>Q96LE7
MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGEQQWKSEKQREAELKKKKLEQ
RSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDEYKR
TALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLDVLKLLLNKGAKISARDKLLSTALHVAVRTGH
YECAEHLIACEADLNAKDREGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTKAIFDSLRE
NSYKTSRIATF
<210> SEQ ID NO 345
<211> Length: 319
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 345
>Q15327
MMVLKVEELVTGKKNGNGEAGEFLPEDFRDGEYEAAVTLEKQEDLKTLLAHPVTLGEQQWKSEKQREAELPKKKLEQ 653 RSKLENLEDLEIIIQLKKRKKYRKTKVPVVKEPEPEIITEPVDVPTFLKAALENKLPVVEKFLSDKNNPDVCDEYKR
TALHRACLEGHLAIVEKLMEAGAQIEFRDMLESTAIHWASRGGNLDVLKLLLNKGAKISARDKLLSTALHVAVRTGH
YECAEHLIACEADLNAKDREGDTPLHDAVRLNRYKMIRLLIMYGADLNIKNCAGKTPMDLVLHWQNGTKAIFDSLRE
NSYKTSRIATF
<210> SEQ ID NO 346
<211> Length: 699
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 346
>SRCH_HUMAN_V1
MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAGLSEEASAELRHHLHSPRDHPDENKDVSTE
NGHHFWSHPDREKEDEDVAKEYGHLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPS
HRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGH
HHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDD
DVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV
QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMS
HHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEED
KEEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQ
EYGNYQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQHCQFCYLCPLVCETVCAPGSYVDYFSSSLYQALADM
LETPEP
<210> SEQ ID NO 347
<211> Length: 419
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 347 >KCRS_HUMAN_V1 MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRKHNNCMAECLTPA IYAKLRNKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEESYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDAS KITQGQFDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDH FLFDKPVSPLLTCAGMARDWPDARGIWHNYDKTFLI INEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQERG WEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSKILENLRLQKRGTGGVDTAAVADVYDISNIDRIGRS EVELVQIVIDGVNYLVDCEKKLERGQDIKVPPPLPQFGKK
<210> SEQ ID NO 348 654 <211> Length: 132
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 348
>Fatty acid-bmdmg protein, heart VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFD ETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA
<210> SEQ ID NO 349
<211> Length: 399
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 349
>Calsequestrιn, cardiac muscle isoform precursor MKRTHLFIVGIYFLSSCRAEEGLNFPTYDGKDRVVSLSEKNFKQVLKKYDLLCLYYHEPVSSDKVTQKQFQ LKEIVLELVAQVLEHKAIGFVMVDAKKEAKLAKKLGFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEI ISSKLEVQAFERIEDYIKLIGFFKSEDSEYYKAFEEAAEHFQPYIKFFATFDKGVAKKLSLKMNEVDFYEPFMDEPI AIPNKPYTEEELVEFVKEHQRPTLRRLRPEEMFETWEDDLNGIHIVAFAEKΞDPDGYEFLEILKQVARDNTDNPDLS ILWIDPDDFPLLVAYWEKTFKIDLFRPQIGVVNVTDADSVWMEIPDDDDLPTAEELEDWIEDVLSGKINTEDDDEDD DDDDNSDEEDNDDSDDDDDE
<210> SEQ ID NO 350
<211> Length: 151
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 350
>Atrial natriuretic factor precursor MSSFSTTTVSFLLLLAFQLLGQTRANPMYNAVSNADLMDFKNLLDHLEEKMPLEDEVVPPQVLSEPNEEAG AALSPLPEVPPWTGEVSPAQRDGGALGRGPWDSSDRSALLKSKLRALLTAPRSLRRSSCFGGRMDRIGAQSGLGCNS FRY
<210> SEQ ID NO 351
<211> Length: 209
<212> Type: PRT
<213> ORGANISM: Homo sapiens 655
<400> sequence: 351
>Troponιn I, cardiac muscle, known protein ADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQELEREAEERRGEKG RALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTLRRVRIS ADAMMQALLGARAKESLDLRAHLKQVKKEDTEKENREVGDWRKNIDALSGMEGRKKKFES <210> SEQ ID NO 352 <211> Length: 175 <212> Type: PRT <213> ORGANISM: Homo sapiens
<400> sequence: 352
>Troponιn I, cardiac muscle, variant from SNP MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQELEREAEERRGE KGRALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPTLRRVR ISADAMMQALLGARAKESWTCGPTSSR
<210> SEQ ID NO 353
<211> Length: 846
<212> Type: DNA
<213> ORGANISM: Homo sapiens
<400> sequence: 353
> HUMTROPIA_T0_ SNP646 #LN 846
TCTCAGTGTCCTCGGGGAGTCTCAAGCAGCCCGGAGGAGACTGACGGTCCCTGGGACCCT
GAAGGTCACCCGGGCGGCCCCCTCACTGACCCTCCAAACGCCCCTGTCCTCGCCCTGCCT
CCTGCCATTCCCGGCCTGAGTCTCAGCATGGCGGATGGGAGCAGCGATGCGGCTAGGGAA
CCTCGCCCTGCACCAGCCCCAATCAGACGCCGCTCCTCCAACTACCGCGCTTATGCCACG
GAGCCGCACGCCAAGAAAAAATCTAAGATCTCCGCCTCGAGAAAATTGCAGCTGAAGACT
CTGCTGCTGCAGATTGCAAAGCAAGAGCTGGAGCGAGAGGCGGAGGAGCGGCGCGGAGAG
AAGGGGCGCGCTCTGAGCACCCGCTGCCAGCCGCTGGAGTTGGCCGGGCTGGGCTTCGCG
GAGCTGCAGGACTTGTGCCGACAGCTCCACGCCCGTGTGGACAAGGTGGATGAAGAGAGA
TACGACATAGAGGCAAAAGTCACCAAGAACATCACGGAGATTGCAGATCTGACTCAGAAG
ATCTTTGACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGATCTCTGCA
GATGCCATGATGCAGGCGCTGCTGGGGGCCCGGGCTAAGGAGTCCTGGACCTGCGGGCCC
ACCTCAAGCAGGTGAAGAAGGAGGACACCGAGAAGGAAAACCGGGAGGTGGGAGACTGGC
GCAAGAACATCGATGCACTGAGTGGAATGGAGGGCCGCAAGAAAAAGTTTGAGAGCTGAG 656
CCTTCCTGCCTACTGCCCCTGCCCTGAGGAGGGCCCTGAGGAATAAAGCTTCTCTCTGAG CTGAAA
<210> SEQ ID NO 354
<211> Length: 85
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 354
>CDS-1 frame 1 from 148 to 406 length 259 (bp) = 86 (aa) (similar to Troponin I N-ter)
MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKVGRGFLGAEYRRRRDPRPWEWGE EPGLRRGRGLRGGASGAEFCRGSCSDW
<210> SEQ ID NO 355
<211> Length: 185
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 355
>CDS-2 frame 1 from 628 to 1183 length 556 (bp) = 185 (aa) (similar to
Troponin I C-ter)
MILPCSISPWQKKSKISASRKLQLKTLLLQIAKQELEREAEERRGEKGRALSTRCQPLE
LAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTKNITEIADLTQKIFDLRGKFKRPT
LRRVRISADAMMQALLGARAKESLDLRAHLKQVKKEDTEKENREVGDWRKNIDALSGME
GRKKKFES
<210> SEQ ID NO 356
<211> Length: 158
<212> Type: PRT
<213> ORGANISM: Homo sapiens
<400> sequence: 356
>CDS-3 frame 2 from 155 to 629 length 475 (bp) = 158 (aa) (Not similar to
Troponin I)
MGAAMRLGNLALHQPQSDAAPPTTALMPRSRTPRWDGASWGQSTGAGGIQDPGSGGRSQ 657
GCEGGGDYAEGLQGRSFAEGHARIGDSSLRAELRCPRTCLGIDGKCLSKGRDPDWWMGM RGVASRRLRAQVGRGPKSGPAGFAGGVLRSPPPSSPNPPP
<210> SEQ ID NO 357
<211> Length: 20
<212> Type: DNA
<213> ORGANISM: artificial sequence
<400> sequence: 357 >Tropfor CCCTCACTGACCCTCCAAAC
<210> SEQ ID NO 358
<211> Length: 20
<212> Type: DNA
<213> ORGANISM: artificial sequence
<400> sequence: 358 >TropRev
CTTCCCATCTATCCCTAAGC
<210> SEQ ID NO 359
<211> Length: 27
<212> Type: DNA
<213> ORGANISM: artificial sequence
<400> sequence: 359
> Trop Nhelfor ACAGCTAGCATGGCGGATGGGAGCAGC
<210> SEQ ID NO 360
<211> Length: 27
<212> Type: DNA
<213> ORGANISM: artificial sequence 658 <400> sequence: 360
> TropHindlllrev
CCTAAGCTTCACCAATCCGAGCATGAC
<210> SEQ ID NO 361
<211> Length: 113
<212> Type: DNA
<213> ORGANISM: artificial sequence
<400> sequence: 361 >N56180 seg
TTGATACCACTTAGTGTAGCTCCAGCATGGATCAGCAAACTTTTTCTGTAAAGAACAAAATGGTAAATATTTCAGGT TCTGTGGGCCAGATGGCGTCTGTAGCAACTACTTGA
SEQ ID NO 362
>Q96NF5
MLRSTSTVTLLSGGAARTPGAPSRRANVCRLRLTVPPESPVPEQCEKKIERKEQLLDLSN
GEPTRKLPQGVVYGVVRRSDQNQQKEMVVYGWSTSQLKEEMNYIKDVRATLEKVRKRMYG
DYDEMRQKIRQLTQELSVSHAQQEYLENHIQTQSSALDRFNAMNSALASDSIGLQKTLVD
VTLENSNIKDQIRNLQQTYEASMDKLREKQRQLEVAQVENQLLKMKVESSQEANAEVMRE
MTKKLYSQYEEKLQEEQRKHSAEKEALLEETNSFLKVIEEANKKMQAAEISLEEKDQRIG
ELDRLIERMEKERHQLQLQLLEHETEMSGELTDSDKERYQQLEEASASLRERIRHLDDMV
HCQQKKVKQMVEEIESLKKKLQQKQLLILQLLEKISFLEGENNELQSRLDYLTETQAKTE
VETREIGVGCDLLPSQTGRTREIVMPSRNYTPYTRVLELTMKKTLT
SEQ ID NO 363
>T10377 ]unc25-31F
AGCAGATGGTCGAGGAGAATAATG
SEQ ID NO 364 >T10377 junc25-31R ATCTCTCTGGTTTCCACTTCGG
SEQ ID NO 365 >T10377 ]unc25-31
AGCAGATGGTCGAGGAGAATAATGAACTACAAAGCAGGTTGGACTATTTAACAGAAACCCAGGCCAAGACCGAAGTG GAAACCAGAGAGAT 659 SEQ ID NO 366
>T10377 ]unc29-33F
CTTTCTTAGAAGGAGAGCCAAACAG
SEQ ID NO 367
>T10377 ]unc29-33R
CCTAAGTCAGAGTTTTCTTCATGGTTAAC
SEQ ID NO 368 >T10377 ]unc29-33
CTTTCTTAGAAGGAGAGCCAAACAGGCAGGACTCGTGAAATTGTGATGCCTTCTAGGAACTACACCCCATACACAAG AGTCCTGGAGTTAACCATGAAGAAAACTCTGACTTAGG
SEQ ID NO 369 >T10377 seg2-3F CTTCGCATTGTGCATAACACAA
SEQ ID NO 370
>T10377 seg2-3R
GAAACTCGGATACACAATCTCCAGA
SEQ ID NO 371 >T10377 seg2-3
CTTCGCATTGTGCATAACACAAGCCCTGAACCAGCTGCTTTGGGAACCCCTGGGAATAAAGTGCCCTACCTGCCTTT CAGGCACTGCCAAGCCTGGGGCATCTCTGGAGATTGTGTATCCGAGTTTC
SEQ ID NO 372
>Q9NPI5
MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQ DVLESL
DMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSYKPLVDLYSRRYFL
TVPYEECK RRSTRNYTVPDPPGLFDGHVWPMYQKYRQEMEANGVEVVYLDGMKSREELF
REVLEDIQNSLLNRSQESAPSPARPARTQGPGRGCGHRTARPAASQQDSM
SEQ ID NO 373
>Q9NZK3
MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLESL
DMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSYKPQKYRQEMEANG
VEVVYLDGMKSREELFREVLEDIQNSLLNRSQESAPSPARPARTQGPGRGCGHRTARPAA 660
SQODSM
SEQ ID NO 374
>Forward primer HUMCDDANF3unc2-5F2
CTTCTCCACCACCACCAATTTG
SEQ ID NO 375
>Reverse primer HUMCDDANF]unc2-5R2
GAGAGCAGCCCCCGCT
SEQ ID NO 376
>Amplιcon HUMCDDANF;)unc2-5F2R2
CTTCTCCACCACCACCAATTTGCTGGACCATTTGGAAGAAAAGATGCCTTTAGAAGATGAGGTCGTGCCCCCACAAG
TGCTCAGTGAGCCGAATGAAGAAGCGGGGGCTGCTCTC
SEQ ID NO 377
>HUMTROPIA segl Forward primer
TTGCAGAGGGTCATGCTCG
SEQ ID NO 378
>HUMTROPIA segl Reverse primer
TCCTTTGGATAGGCACTTCCC
SEQ ID NO 379 >HUMTROPIA segl Amplicon
TTGCAGAGGGTCATGCTCGGATTGGTGACAGCAGCCTGCGGGCGGAACTCCGTTGCCCTCGGACTTGCTTAGGGATA GATGGGAAGTGCCTATCCAAAGGA
SEQ ID NO 380
>HUMTROPIA seg22 Forward primer
GTGGGACGCATGGGCA
SEQ ID NO 381
>HUMTROPIA seg22 Reverse primer
TTGTCCTGGGTCTCCTGGG
SEQ ID NO 382
>HUMTROPIA seg22 Amplicon 661
GTGGCACGCATGGGCAGCTCGGGTACCTTCGGGGTAGGGTGAGATGGCTGGGACTTGGTCTCTGCCTGACCCCTTGC
AGCTGCTTTTGGCTGCACATCCCAGGAGACCCAGGACAA
SEQ ID NO 383
>Forward primer HUMTROPIA seg23-24-25F
AAGATCTTTGACCTTCGAGGCA
SEQ ID NO 384
>Reverse primer HUMTROPIA seg23-24-25R
CTGCTTGAGGTGGGCCC
SEQ ID NO 385
>Amplιcon HUMTROPIA seg23-24-25
AAGATCTTTGACCTTCGAGGCAAGTTTAAGCGGCCCACCCTGCGGAGAGTGAGGATCTCTGCAGATGCCATGATGCA
GGCGCTGCTGGGGGCCCGGGCTAAGGAGTCCCTGGACCTGCGGGCCCACCTCAAGCAG
SEQ ID NO 386
> DNA sequence of HisTroponin T7 pRSETA
GATCTCGATCCCGCGAAATTAATACGACTCACTATAGGGAGACCACAACGGTTTCCCTCTAGAAATAATTTTGTTTA
ACTTTAAGAAGGAGATATACATATGCGGGGTTCTCATCATCATCATCATCATGGTATGGCTAGCATGGCGGATGGGA
GCAGCGATGCGGCTAGGGAACCTCGCCCTGCACCAGCCCCAATCAGACGCCGCTCCTCCAACTACCGCGCTTATGCC
ACGGAGCCGCACGCCAAGGTGGGACGGGGCTTCCTGGGGGCAGAGTACAGGCGCCGGAGGGATCCAAGACCCTGGGA
GTGGGGGGAGGAGCCAGGGCTGCGAAGGGGGCGGGGACTACGCGGAGGGGCTTCAGGGGCGGAGTTTTGCAGAGGGT
CATGCTCGGATTGGTGAAGCTTGATCCGGCTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTG
AGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATATCC
GGATCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGGAC
GCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCT
AGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGG
GGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGT
AGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTT
CCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATT
GGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGCTTACAATTTAGGTGGCA
CTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATG
TATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTT
CCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA
AAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGT
TTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGA
CGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAA 662 AGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAAC
TTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCT
TGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAA
CAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCG
GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGA
GCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGG
GGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTG
TCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGAT
CCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGA
TCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAA
CCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAG
AGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTA
CATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCA
AGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAAC
GACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACA
GGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTAT
AGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAA
AAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTAT
CCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGC
AGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTA
ATGCAG
SEQ ID NO 387
>HIS-TAG TROPONIN I VARIANT
MRGSHHHHHHGMASMADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKVGRGFLGAEYRRRRDPRPWEWGEEPGL
RRGRGLRGGASGAEFCRGSCSDW
SEQ ID NO 388
>Creatme kinase, sarcomeric mitochondrial precursor
MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLRKHNNCMAECLTPAIYSKLR
NKVTPNGYTLDQCIQTGVDNPGHPFIKTVGMVAGDEEΞYEVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKITQGQ
FDEHYVLSSRVRTGRSIRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLFDKP
VSPLLTCAGMARDWPDARGIWHNYDKTFLI INEEDHTRVISMEKGGNMKRVFERFCRGLKEVERLIQERGWEFM N
ERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSKILENLRLQKRGTGGVDTAAVADVYDISNIDRIGRSEVELVQ
IVIDGVNYLVDCEKKLERGQDIKVPPPLPQFGKK
SEQ ID NO 389
>Sarcoplasmιc reticulum histidine-rich calcium-binding protein precursor 663 MGHHRPWLHASVLWAGVASLLLPPAMTQQLRGDGLGFRNRNNSTGVAGLSEEASAELRHHLHSPRDHPDENKDVSTE
NGHHFWSHPDREKEDEDVSKEYGHLLPGHRSQDHKVGDEGVSGEEVFAEHGGQARGHRGHGSEDTEDSAEHRHHLPS
HRSHSHQDEDEDEVVSSEHHHHILRHGHRGHDGEDDEGEEEEEEEEEEEEASTEYGHQAHRHRGHGSEEDEDVSDGH
HHHGPSHRHQGHEEDDDDDDDDDDDDDDDDVSIEYRHQAHRHQGHGIEEDEDVSDGHHHRDPSHRHRSHEEDDNDDD
DVSTEYGHQAHRHQDHRKEEVEAVSGEHHHHVPDHRHQGHRDEEEDEDVSTERWHQGPQHVHHGLVDEEEEEEEITV
QFGHYVASHQPRGHKSDEEDFQDEYKTEVPHHHHHRVPREEDEEVSAELGHQAPSHRQSHQDEETGHGQRGSIKEMS
HHPPGHTVVKDRSHLRKDDSEEEKEKEEDPGSHEEDDESSEQGEKGTHHGSRDQEDEEDEEEGHGLSLNQEEEEEED
KEEEEEEEDEERREERAEVGAPLSPDHSEEEEEEEEGLEEDEPRFTIIPNPLDRREEAGGASSEEESGEDTGPQDAQ
EYGNYQPGSLCGYCSFCNRCTECESCHCDEENMGEHCDQCQHCQFCYLCPLVCETVCAPGSYVDYFSSSLYQALADM
LETPEP
SEQ ID NO 390 hypothetical protein FLJ26352
MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRCWFNGIVEENDΞNIWKFWY
TNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWAVLMLLGVVAVVIASFLIICAAPFASHFLYKAGGGSYI
AAGILFSLVVMLYVIWVQAVADMESYRNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAGLLFLWGRHIQIHH
SEQ ID NO 391
>Myosιn heavy chain, cardiac muscle alpha isoform
MTDAQMADFGAAAQYLRKSEKERLEAQTRPFDIRTECFVPDDKEEFVKAKILSREGGKVIAETENGKTVTVKEDQVL
QQNPPKFDKIQDMAMLTFLHEPAVLFNLKERYAAWMIYTYSGLFCVTVNPYKWLPVYNAEVVAAYRGKKRSEAPPHI
FSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFASIAAIGDRGKKDNANANKGTLEDQIIQANPALEAF
GNAKTVRNDNSSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERNYHIFYQILSNKKPELLDMLLVTNNP
YDYAFVSQGEVSVASIDDSEELMATDSAFDVLGFTSEEKAGVYKLTGAIMHYGNMKFKQKQREEQAEPDGTEDADKS
AYLMGLNSADLLKGLCHPRVKVGNEYVTKGQSVQQVYYSIGALAKAVYEKMFNWMVTRINATLETKQPRQYFIGVLD
IAGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEEC
MFPKATDMTFKAKLYDNHLGKSNNFQKPRNIKGKQEAHFSLIHYAGTVDYNILGWLEKNKDPLNETVVALYQKSSLK
LMATLFSSYATADTGDSGKSKGGKKKGSSFQTVSALHRENLNKLMTNLRTTHPHFVRCIIPNERKAPGVMDNPLVMH
QLRCNGVLEGIRICRKGFPNRILYGDFRQRYRILNPVAIPEGQFIDSRKGTEKLLSSLDIDHNQYKFGHTKVFFKAG
LLGLLEEMRDERLSRIITRMQAQARGQLMRIEFKKIVERRDALLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAET
EKEMATMKEEFGRIKETLEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLNDAEERCDQLIKNKIQLEAKVKEM
NERLEDEEEMNAELTAKKRKLEDECSELKKDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKAL
QEAHQQALDDLQVEEDKVNSLSKSKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKLQL
EEKLKKKEFDINQQNSKIEDEQALALQLQKKLKENQARIEELEEELEAERTARAKVEKLRSDLSRELEEISERLEEA
GGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDD
VTSNMEQIIKAKANLEKVSRTLEDQANEYRVKLEEAQRSLNDFTTQRAKLQTENGELARQLEEKEALISQLTRGKLS
YTQQMEDLKRQLEEEGKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTE
ELEEAKKKLAQRLQDAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAAALDKKQRNFDKILAEWKQKYE 664 ESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGEGGKNVHELEKVRKQLEVEKL
ELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIERKLAEKDEEMEQAKRNHQRVVDSLQTSLDAETRSRNEVLRVK
KKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNLLQAELEELRAVV
EQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMEADLTQLQSEVEEAVQECRNAEEKAKKAITDAAMMAEEL
KKEQDTSAHLERMKKNMEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEGELEAEQKRNAESVKGMRKSERR
IKELTYQTEEDKKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKLRAK
SRDIGAKQKMHDEE
SEQ ID NO 392
>S67314_0_0_741
CACAGAGCCAGGATGTTCTTCTGACCTCAGTATCTACTCCAGCTCCAGCT
SEQ ID NO 393
>S67314_0_0_744
TGGCATGCTGGAACATGGACTCTAGCTAGCAAGAAGGGCTCAAGGAGGTG

Claims

665 WHAT IS CLAIMED IS:
1. An isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NOs: 22-25, 353 or 386, or a polynucleotide at least about 95% homologous thereto.
2. An isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 130-149, or a polynucleotide at least about 95% homologous thereto.
3. An isolated polypeptide comprising a protein variant selected from the group consisting of SEQ ID NOs: 301-304, 325, 354-356 or 387, or a polypeptide at least about 95% homologous thereto.
4. An isolated chimeric polypeptide encoding for SEQ ID NO. 301, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 124 of TRIC_HUMAN, which also conesponds to amino acids 1 - 124 of SEQ ID NO. 301, 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 sequence conesponding to amino acids 125- 137 of SEQ ID NO. 301, wherein said first and second amino acid sequences are contiguous and in a sequential order.
5. An isolated polypeptide encoding for a tail of SEQ ID NO. 301, 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 VGRMGSSGTFGVG in SEQ ID NO. 301.
6. An isolated chimeric polypeptide encoding for SEQ ID NO. 302, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 8 of TRIC HUMAN, which also coπesponds to amino acids 1 - 8 of SEQ ID NO. 302, and a second 666 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 sequence conesponding to amino acids 36 - 209 of TRIC HUMAN, which also coπesponding to amino acids 9 - 182 of SEQ ID NO. 302, wherein said first and second amino acid sequences are contiguous and in a sequential order.
7. An isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 302, 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 AK, having a structure as follows: a sequence starting from any of amino acid numbers 8-x to 8; and ending at any of amino acid numbers 9+ ((n-2) - x), in which x varies from 0 to n-2.
8. An isolated chimeric polypeptide encoding for SEQ ID NO. 303, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 36 of TRIC HUMAN, which also coπesponds b amino acids 1 - 36 of SEQ ID NO. 303, 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 sequence coπesponding to amino acids 37- 86 of SEQ ID NO. 303, wherein said first and second amino acid sequences are contiguous and in a sequential order.
9. An isolated polypeptide encoding for a tail of SEQ ID NO. 303, 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 VGRGFLGAEYRRRPvDPRPWEWGEEPGLRRGRGLRGGASGAEFCRGSCSDW in SEQ ID NO. 303.
10. An isolated chimeric polypeptide encoding for SEQ ID NO. 304, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 8 of TRIC_HUMAN, which also coπesponds to amino acids 1 - 8 of SEQ ID NO. 304, and a second 667 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 sequence conesponding to amino acids 9- 13 of SEQ ID NO. 304, wherein said first and second amino acid sequences are contiguous and in a sequential order.
1 1. An isolated polypeptide encoding for a tail of SEQ ID NO. 304, 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 VRAAG in SEQ ID NO. 304.
12. An isolated oligonucleotide, comprising an amplicon selected from the group consisting of SEQ ID NOs: 379, 382 or 385.
13. A primer pair, comprising a pair of isolated oligonucleotides capable of amplifying said amplicon of claim 12.
14. The primer pair of claim 13, comprising a pair of isolated oligonucleotides selected from the group consisting of: SEQ NOs 377 and 378; 380 and 381; or 383 and 384.
15. An antibody capable of specifically binding to an epitope of an amino acid sequence of any of claims 3-11.
16. The antibody of claim 15, wherein said amino acid sequence comprises one of: a tail of SEQ ID NO. 301, comprising a polypeptide being at least 70 homologous to the sequence VGRMGSSGTFGVG in SEQ ID NO. 301 ; a tail of SEQ ID NO. 303, comprising a polypeptide being at least 70% homologous to the sequence
VGRGFLGAEYRRRRDPRPWEWGEEPGLRRGRGLRGGASGAEFCRGSCSDW in SEQ ID NO. 303; a tail of SEQ ID NO. 304, comprising a polypeptide being at least 70% homologous to the sequence VRAAG in SEQ ID NO. 304; or 668 an edge portion of SEQ ID NO. 302, comprising a polypeptide having a length "n", wherein "n" is at least about 10 amino acids in length, wherein at least two amino acids comprise AK, having a structure as follows: a sequence starting from any of amino acid numbers 8-x to 8; and ending at any of amino acid numbers 9+ ((n-2) - x), in which x varies from 0 to n-2.
17. The antibody of claims 15, wherein said antibody is capable of differentiating between a splice variant having said epitope and a coπesponding known protein TRIC_HUMAN.
18. A kit for detecting heart disorders, comprising a kit detecting overexpression of a splice variant according to any of claims 1 - 1 1.
19. The kit of claim 18, wherein said kit comprises a NAT-based technology.
20. The kit of claim 19, wherein said kit further comprises at least one primer pair capable of selectively amplifying the nucleic acid sequence.
21. The kit of claim 18, wherein said kit further comprises at least one oligonucleotide capable of selectively hybridizing to the nucleic acid sequence.
22. A kit for detecting heart disorders, comprising a kit an antibody according of claim 15.
23. The kit of claim 22, wherein said kit further comprises at least one reagent for performing an ELISA or a Western blot.
24. A method for detecting heart disorders, comprising detecting overexpression of a splice variant according to any of claims 1-11.
25. The method of claim 24, wherein said detecting overexpression is performed 669 with a NAT-based technology.
26. The method of claim 24, wherein said detecting overexpression is performed with an immunoassay.
27. The method of claim 26, wherein said immunoassay comprises an antibody.
28. A biomarker capable of detecting heart disorders, comprising the nucleic acid sequences or a fragment thereof, or amino acid sequences or a fragment thereof of any of claims 1- 12.
29. A method for screening for heart disorders, comprising detecting heart disorder cells using the biomarkers or antibodies of any of claims 1- 12.
30. A method for diagnosing heart disorders, comprising detecting heart disorder cells using the biomarkers or antibodies of any of claims 1-12.
31. A method for monitoring disease progression, or treatment efficacy, or relapse of heart disorders, or any combination thereof, comprising detecting heart disorder cells using the biomarkers or antibodies or a method or assay according to any of claims 1-12.
32. A method of selecting a therapy for heart disorders, comprising detecting heart disorder cells with any of the above biomarkers or antibodies or a method or assay according to any of claims 1-12 and selecting a therapy according to said detection.
33. A method according to claim 28, wherein a heart disorder and/or cardiac disease and/or cardiac pathology comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, or assessing the size of infarct in Myocardial infarct.
670 34. A method according to claim 29, wherein a heart disorder and/or cardiac disease and/or cardiac pathology comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, or assessing the size of infarct in Myocardial infarct.
35. A method according to claim 30, wherein a heart disorder and/or cardiac disease and/or cardiac pathology comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, or assessing the size of infarct in Myocardial infarct.
36. A method according to claim 31 , wherein a heart disorder and/or cardiac disease and/or cardiac pathology comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, or assessing the size of infarct in Myocardial infarct.
37. A method according to claim 32, wherein a heart disorder and/or cardiac disease and/or cardiac pathology comprises at least one of: Myocardial infarct, ungina pectoris (stable and unstable), cardiomyopathy, myocarditis, congestive heart failure, the detection of reinfarction, the detection of success of thrombolytic therapy after Myocardial infarct, Myocardial infarct after surgery, or assessing the size of infarct in Myocardial infarct.
EP05726249A 2004-01-27 2005-01-27 Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease Withdrawn EP1713827A2 (en)

Applications Claiming Priority (11)

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US53912904P 2004-01-27 2004-01-27
US53912804P 2004-01-27 2004-01-27
US62091604P 2004-10-22 2004-10-22
US62113104P 2004-10-25 2004-10-25
US62232004P 2004-10-27 2004-10-27
US62812304P 2004-11-17 2004-11-17
US62819004P 2004-11-17 2004-11-17
US62813404P 2004-11-17 2004-11-17
US63055904P 2004-11-26 2004-11-26
PCT/IB2005/001306 WO2005069724A2 (en) 2004-01-27 2005-01-27 Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of cardiac disease
US11/043,788 US20060014166A1 (en) 2004-01-27 2005-01-27 Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of endometriosis

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