Novel bap28 gene and protein
AssigneeSerono Genetics Institute S.A.
InventorsCaroline Barry, Lydie Bougueleret, Ilya Chumakov, Annick Cohen-Akenine
Life of this patent
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Abstract
The present invention is directed to BAP28 polypeptides. BAP28 cDNA sequences encoding BAP28 polypeptides, to the genomic DNA sequence of the BAP28 gene as well as to regulatory regions located at the 5′- and 3′-ends of the BAP28 coding region. The invention also deals with antibodies directed specifically against such polypeptides that are useful as diagnostic reagents. The invention further encompasses biallelic markers of the BAP28 gene useful in genetic analysis. The invention concerns an association of the BAP28-related biallelic markers with prostate cancer. Therefore, the invention contemplates the diagnostic and treatment methods of prostate cancer.
Claims29
A purified or isolated BAP28 nucleic acid comprising:
- a) a contiguous span of at least 12 nucleotides of SEQ ID No 1, wherein said contiguous span comprises at least of the following nucleotide positions of SEQ ID No 1:
- 1-50357, 50499-50963, 51257-52147, 52299-53234, 53394-53553, 53689-53837, 53943-54028, 54198-54740, 54896-55753, 55913-57385, 57495-58503, 58828-85946, 59355-85946, 86169-91228, or 91852 to 97662;
- b) a contiguous span of at least 12 nucleotides of SEQ ID No 1 or the complement thereof, wherein said contiguous span comprises at least 1 nucleotides selected from the group consisting of the following nucleotide positions of SEQ ID No 1:
- 4997-5076, 5371-5544, 6121-6337, 9877-10018, 11522-11623, 12521-12661, 13453-13664, 13824-13957, 15376-15478, 16855-16965, 17378-17495, 18535-18642, 21446-21541, 21999-22087, 23036-23247, 23546-23667, 24270-24461, 26287-26470, 26611-26747, 28068-28260, 32540-32709, 33112-33270, 34586-34828, 35156-35287, 36660-36763, 36934-37077, 37803-37921, 38017-38138, 40365-40493, 42618-42848, 43452-43578, 44836-44999, 48223-48269, or 49656-49779;
- c) a contiguous span of at least 12 nucleotides of SEQ ID No 1 or the complements thereof, wherein said contiguous span comprises at least one BAP28-related biallelic marker selected from the group consisting of A1 to A58;
- d) a contiguous span of at least 12 nucleotides of a nucleic acid sequence selected from the group consisting of SEQ ID Nos 2 and 3 or the complements thereof, wherein said contiguous span comprises at least 1 of nucleotide positions 1 to 4995 of SEQ ID No 2 or 3;
- e) a contiguous span of at least 12 nucleotides of a nucleic acid sequence selected from the group consisting of SEQ ID Nos 2 and 3 or the complements thereof, wherein said contiguous span comprises at least 1 of nucleotide positions 1 to 2033, 2160 to 2348 and 2676 to 4995 of SEQ ID No 2 or 3;
- f) a contiguous span of at least 12 nucleotides of a nucleic acid sequence selected from the group consisting of SEQ ID Nos 1-3 or the complements thereof, wherein said contiguous span comprises at least 1 of any one of the following ranges of nucleotide positions of:
- (1) SEQ ID No 1:1-2500, 2501-5000, 5001-7500, 7501-10000, 10001-12500, 12501-15000, 15001-17500, 17501-20000, 20001-22500, 22501-25000, 25001-27500, 27501-30000, 30001-32500, 32501-35000, 35001-37500, 37501-40000, 40001-42500, 42501-45000, 45001-47500, 47501-50000, 50001-50357, 50499-50963, 51257-52147, 52299-53234, 53394-53553, 53689-53837, 53943-54028, 54198-54740, 54896-55753, 55913-57385, 57495-58503, 58828-85946, 59355-85946, 86169-911228, or 91852 to 97662;
- (2) SEQ ID No 2:
- 1 to 500, 501 to 1000, 1001 to 1500, 1501 to 2000, 2001 to 2500, 2501 to 3000, 3001 to 3500, 3501 to 4000, 4001 to 4500, 4501 to 4995, 5000 to 5500, 5501 to 6000, 6001 to 6500, or 6501 to 6782;
- or
- (3) SEQ ID No 3:
- 1 to 500, 501 to 1000, 1001 to 1500, 1501 to 2000, 2001 to 2500, 2501 to 3000, 3001 to 3500, 3501 to 4000, 4001 to 4500, 4501 to 4995, 5000 to 5500, 5501 to 6000, 6001 to 6500, 6501 to 7000, 7001 to 7500 or 7501 to 7932;
- g) a nucleotide sequence selected from the group consisting of SEQ ID Nos 4, and 9-13;
- h) a nucleotide sequence complementary to any one of the preceding nucleotide sequences;
- i) a polynucleotide which encodes a polypeptide comprising a contiguous span of at least 6 amino acids of SEQ ID No 5, wherein said contiguous span includes:
- at least 1 of the amino acid positions 1 to 1629 of the SEQ ID No 5;
- or,
- an amino acid selected from the group consisting of an asparagine at the amino acid position 1694 of SEQ ID No 5, a valine at the amino acid position 1854 of SEQ ID No 5, an asparagine at the amino acid position 1967 of SEQ ID No 5, a glutamic acid at the amino acid position 2017 of SEQ ID No 5, and an alanine at the amino acid position 2050 of SEQ ID No 5;
- j) comprising a sequence selected from the group consisting of SEQ ID Nos 4, and 9-13 and the complementary sequence thereto.
- k) a polynucleotide that consists essentially of a sequence selected from the following sequences:
- P1 to P58, and the complementary sequences thereto.
- l) a polynucleotide that consists essentially of a sequence selected from the following sequences:
- D1 to D58 and E1 to E58;
- m) a polynucleotide that consists essentially of a sequence selected from the following sequences:
- B1 to B338 and C1 to C38.
A method of genotyping comprising determining the identity of a nucleotide at a BAP28-related biallelic marker or the complement thereof in a biological sample, said BAP28-related biallelic marker being selected from one or more of the biallelic markers A1 to A58.
An isolated, purified, or recombinant polypeptide comprising a contiguous span of at least 6 amino acids of SEQ ID No 5, wherein said contiguous span includes:
- at least 1 of the amino acid positions 1 to 1629 of the SEQ ID No 5;
- or,
- an amino acid selected from the group consisting of an asparagine at the amino acid position 1694 of SEQ ID No 5, a valine at the amino acid position 1854 of SEQ ID No 5, an asparagine at the amino acid position 1967 of SEQ ID No 5, a glutamic acid at the amino acid position 2017 of SEQ ID No 5, and an alanine at the amino acid position 2050 of SEQ ID No 5.
A method for screening of a candidate substance that modulated the expression of the BAP28 gene comprising the following steps:
- a) providing a recombinant cell host containing a nucleic acid, wherein said nucleic acid comprises a nucleotide sequence of the 5′ regulatory region (2996-4996 of SEQ ID No 1) or a biologically active fragment or variant thereof located upstream a polynucleotide encoding a detectable protein;
- obtaining a candidate substance;
- and
- determining the ability of the candidate substance to modulate the expression levels of the polynucleotide encoding the detectable protein.
A computer readable medium having stored thereon a sequence selected from the group consisting of a nucleic acid code comprising one of the following:
- a) a contiguous span of at least 12 nucleotides of SEQ ID No 1, wherein said contiguous span comprises at least 1 of the following nucleotide positions of SEQ ID No 1:1-50357, 50499-50963, 51257-52147, 52299-53234, 53394-53553, 53689-53837, 53943-54028, 54198-54740, 54896-55753, 55913-57385, 57495-58503, 58828-85946, 59355-85946, 86169-91228, and/or 91852 to 97662:
- b) a contiguous span of at least 12 nucleotides of SEQ ID No 1 or the complement thereof, wherein said contiguous span comprises at least 1 nucleotides selected from the group consisting of the following nucleotide positions of SEQ ID No 1:
- 4997-5076, 5371-5544, 6121-6337, 9877-10018, 11522-11623, 12521-12661, 13453-13664, 13824-13957, 15376-15478, 16855-16965, 17378-17495, 18535-18642, 21446-21541, 21999-22087, 23036-23247, 23546-23667, 24270-24461, 26287-26470, 26611-26747, 28068-28260, 32540-32709, 33112-33270, 34586-34828, 35156-35287, 36660-36763, 36934-37077, 37803-37921, 38017-38138, 40365-40493, 42618-42848, 43452-43578, 44836-44999, 48223-48269, and 49656-49779;
- c) a contiguous span of at least 12 nucleotides of SEQ ID No 1 or the complements thereof, wherein said contiguous span comprises at least one BAP28-related biallelic marker selected from the group consisting of A1 to A58:
- d) a contiguous span of at least 12 nucleotides of a nucleic acid sequence selected from the group consisting of SEQ ID Nos 2 and 3 or the complements thereof, wherein said contiguous span comprises at least 1 of nucleotide positions 1 to 4995 of SEQ ID No 2 or 3;
- e) a contiguous span of at least 12 nucleotides of a nucleic acid sequence selected from the group consisting of SEQ ID Nos 2 and 3 or the complements thereof, wherein said contiguous span comprises at least 1 of nucleotide positions 1 to 2033, 2160 to 2348 and 2676 to 4995 of SEQ ID No 2 or 3;
- f) a contiguous span of at least 12 nucleotides of a nucleic acid sequence selected from the group consisting of SEQ ID Nos 1-3 or the complements thereof, wherein said contiguous span comprises at least 1 of any one of the following ranges of nucleotide positions of:
- (1) SEQ ID No 1:1-2500, 2501-5000, 5001-7500, 7501-10000, 10001-12500, 12501-15000, 15001-17500, 17501-20000, 20001-22500, 22501-25000, 25001-27500, 27501-30000, 30001-32500, 32501-35000, 35001-37500, 37501-40000, 40001-42500, 42501-45000, 45001-47500, 47501-50000, 50001-50357, 50499-50963, 51257-52147, 52299-53234, 53394-53553, 53689-53837, 53943-54028, 54198-54740, 54896-55753, 55913-57385, 57495-58503, 58828-85946, 59355-85946, 86169-91228, and/or 91852 to 97662:
- (2) SEQ ID No 2:
- 1 to 500, 501 to 1000, 1001 to 1500, 1501 to 2000, 2001 to 2500, 2501 to 3000, 3001 to 3500, 3501 to 4000, 4001 to 4500, 4501 to 4995, 5000 to 5500, 5501 to 6000, 6001 to 6500, and 6501 to 6782;
- and,
- (3) SEQ ID No 3:
- 1 to 500, 501 to 1000, 1001 to 1500, 1501 to 2000, 2001 to 2500, 2501 to 3000, 3001 to 3500, 3501 to 4000, 4001 to 4500, 4501 to 4995, 5000 to 5500, 5501 to 6000, 6001 to 6500, 6500 to 7000, 7001 to 7500, 7501 to 7932;
- and
- g) a nucleotide sequence selected from the group consisting of SEQ ID Nos 4, and 9-13, and,
- h) a nucleotide sequence complementary to any one of the preceding nucleotide sequences.
Dependencies are inferred from the claim text.