Diagnosing predisposition to fat deposition and therapeutic methods for reducing fat deposition and treatment of associated conditions
First Claim
1. A method for diagnosing a predisposition to fat deposition in a subject, which comprises detecting the presence or absence of a polymorphic variation associated with fat deposition at a polymorphic site in a P2X4 nucleotide sequence in a nucleic acid sample from a subject, wherein the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of:
- (a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic site;
whereby the presence of the polymorphic variation is indicative of a predisposition to fat deposition in the subject.
1 Assignment
0 Petitions
Accused Products
Abstract
Provided herein are methods for prognosing and diagnosing fat deposition and related disorders (e.g., obesity and non-insulin diabetes dependent mellitus (NIDDM)) in a subject, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for reducing fat deposition and related disorders, and therapeutic methods for reducing fat deposition or treating fat deposition related disorders in a subject. These embodiments are based in part upon an analysis of polymorphic variations of the nucleic acid set forth in SEQ ID NO:1.
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Citations
57 Claims
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1. A method for diagnosing a predisposition to fat deposition in a subject, which comprises detecting the presence or absence of a polymorphic variation associated with fat deposition at a polymorphic site in a P2X4 nucleotide sequence in a nucleic acid sample from a subject, wherein the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of:
-
(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic site;
whereby the presence of the polymorphic variation is indicative of a predisposition to fat deposition in the subject. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method for diagnosing a predisposition to leanness in a subject, which comprises detecting the presence or absence of a polymorphic variation associated with leanness at a polymorphic site in a P2X4 nucleotide sequence in a nucleic acid sample from a subject, wherein the P2X4 nucleotide sequence is selected from the group consisting of:
-
(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a nucleotide sequence of (i), (ii), or (iii) comprising the polymorphic site;
whereby the presence of the polymorphic variation is indicative of leanness in the subject. - View Dependent Claims (16, 17)
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18. A method for identifying a polymorphic variation associated with fat deposition proximal to an incident polymorphic variation associated with fat deposition, which comprises:
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identifying a polymorphic variant proximal to the incident polymorphic variant associated with fat deposition, wherein the incident polymorphic variant is in a P2X4 nucleotide sequence and the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of;
(a) a polynucleotide sequence set forth in SEQ ID NO;
1;
(b) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence encoded by a nucleotide sequence set forth as SEQ ID NO;
1;
or(c) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence that is 90% identical to an amino acid sequence encoded by a nucleotide sequence set forth in SEQ ID NO;
1; and
determining the presence or absence of an association of the proximal polymorphic variant with fat deposition. - View Dependent Claims (19, 20, 21, 22, 23, 25, 26)
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24. A method for diagnosing a predisposition to non-insulin dependent diabetes mellitus (NIDDM) in a subject, which comprises detecting the presence or absence of a polymorphic variation associated with NIDDM at a polymorphic site in a P2X4 nucleotide sequence in a nucleic acid sample from a subject, wherein the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of:
-
(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a nucleotide sequence of (i), (ii), or (iii) comprising the polymorphic site;
whereby the presence of the polymorphic variation is indicative of a predisposition to NIDDM in the subject.
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27. A method for identifying a polymorphic variation associated with NIDDM proximal to an incident polymorphic variation associated with NIDDM, which comprises:
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identifying a polymorphic variant proximal to the incident polymorphic variant associated with NIDDM, wherein the incident polymorphic variant is in a P2X4 nucleotide sequence and the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of;
(a) a polynucleotide sequence set forth in SEQ ID NO;
1;
(b) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence encoded by a nucleotide sequence set forth as SEQ ID NO;
1;
or(c) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence that is 90% identical to an amino acid sequence encoded by a nucleotide sequence set forth in SEQ ID NO;
1; and
determining the presence or absence of an association of the proximal polymorphic variant with NIDDM. - View Dependent Claims (28, 29, 30, 31, 32)
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33. An isolated nucleic acid which comprises a P2X4 nucleotide sequence selected from the group consisting of:
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(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising a polymorphic variation; and
(e) a nucleotide sequence complementary to the nucleotide sequences of (a), (b), (c), or (d);
wherein the P2X4 nucleotide sequence comprises one or more polymorphic variations selected from the group consisting of thymine at position 14744, an adenine at position 14977, a cytosine at position 15046, a thymine at position 21538, a guanine at position 21630, and a single nucleotide deletion at position 25264 of SEQ ID NO;
1. - View Dependent Claims (36, 37)
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34. An oligonucleotide which comprises a nucleotide sequence complementary to a portion of a P2X4 nucleotide sequence selected from the group consisting of:
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(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
wherein the 3′
end of the oligonucleotide is adjacent to a polymorphic variation in the P2X4 nucleotide sequence. - View Dependent Claims (35)
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38. A method for identifying a candidate therapeutic for fat reduction, which comprises:
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(a) introducing a test molecule to a system which comprises a nucleic acid comprising a P2X4 nucleotide sequence selected from the group consisting of;
(i) the nucleotide sequence of SEQ ID NO;
1;
(ii) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(iii) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(iv) a fragment of a nucleotide sequence of (i), (ii), or (iii);
orintroducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv); and
(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein, whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate therapeutic for fat reduction. - View Dependent Claims (39, 40, 41, 42)
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43. A method for reducing fat deposition in a subject, which comprises contacting a P2X4 nucleic acid with one or more cells of a subject in need thereof, wherein the P2X4 nucleic acid comprises a nucleotide sequence selected from the group consisting of:
-
(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a nucleotide sequence of (i), (ii), or (iii);
whereby contacting the one or more cells of the subject with the P2X4 nucleic acid reduces fat deposition.
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44. A method for reducing fat deposition in a subject, which comprises contacting a P2X4 protein with one or more cells of a subject in need thereof, wherein the P2X4 protein is encoded by a P2X4 nucleotide sequence which comprises a polynucleotide sequence selected from the group consisting of:
-
(a) the polynucleotide sequence of SEQ ID NO;
1;
(b) a polynucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a polynucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a polynucleotide sequence of (i), (ii), or (iii);
whereby contacting the one or more cells of the subject with the P2X4 protein reduces fat deposition.
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45. A method for reducing fat deposition in a subject, which comprises:
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detecting the presence or absence of a polymorphic variant associated with fat deposition in a P2X4 nucleotide sequence in a nucleic acid sample from a subject, wherein the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of;
(a) the polynucleotide sequence of SEQ ID NO;
1;
(b) a polynucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a polynucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a polynucleotide sequence of (i), (ii), or (iii); and
administering a treatment that reduces fat deposition to a subject from whom the sample originated where the presence of a polymorphic variation associated with fat reduction is detected in the P2X4 nucleotide sequence. - View Dependent Claims (46, 47)
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48. A method for identifying a candidate therapeutic for alleviating NIDDM, which comprises:
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(a) introducing a test molecule to a system which comprises a nucleic acid comprising a P2X4 nucleotide sequence selected from the group consisting of;
(i) the nucleotide sequence of SEQ ID NO;
1;
(ii) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(iii) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(iv) a fragment of a nucleotide sequence of (i), (ii), or (iii);
orintroducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv); and
(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein, whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate therapeutic for treating NIDDM. - View Dependent Claims (49, 50, 51, 52)
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53. A method for alleviating NIDDM in a subject, which comprises contacting a P2X4 nucleic acid with one or more cells of a subject in need thereof, wherein the P2X4 nucleic acid comprises a nucleotide sequence selected from the group consisting of:
-
(a) the nucleotide sequence of SEQ ID NO;
1;
(b) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a nucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a nucleotide sequence of (i), (ii), or (iii);
whereby contacting the one or more cells of the subject with the P2X4 nucleic acid alleviates NIDDM.
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54. A method for alleviating NIDDM in a subject, which comprises contacting a P2X4 protein with one or more cells of a subject in need thereof, wherein the P2X4 protein is encoded by a P2X4 nucleotide sequence which comprises a polynucleotide sequence selected from the group consisting of:
-
(a) the polynucleotide sequence of SEQ ID NO;
1;
(b) a polynucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a polynucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a polynucleotide sequence of (i), (ii), or (iii);
whereby contacting the one or more cells of the subject with the P2X4 protein alleviates NIDDM.
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55. A method for alleviating NIDDM in a subject, which comprises:
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detecting the presence or absence of a polymorphic variant associated with NIDDM in a P2X4 nucleotide sequence in a nucleic acid sample from a subject, wherein the P2X4 nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of;
(a) the polynucleotide sequence of SEQ ID NO;
1;
(b) a polynucleotide sequence which encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3;
(c) a polynucleotide sequence which encodes a polypeptide that is 90% identical to the amino acid sequence of SEQ ID NO;
2 or SEQ ID NO;
3; and
(d) a fragment of a polynucleotide sequence of (i), (ii), or (iii); and
administering a treatment that alleviates NIDDM to a subject from whom the sample originated where the presence of a polymorphic variation associated with NIDDM is detected in the P2X4 nucleotide sequence. - View Dependent Claims (56, 57)
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Specification