Claims
- 1. An isolated polynucleotide molecule selected from the group consisting of: (i) a polynucleotide comprising a nucleotide sequence encoding PGC-1, wherein said nucleotide sequence contains a mutation of at least one nucleotide relative to the wild-type sequence of PGC-1 and wherein said mutation is associated with type 2 diabetes, and (ii) a polynucleotide comprising a fragment of the nucleotide sequence encoding PGC-1, wherein said fragment contains a mutation of at least one nucleotide relative to the wild-type sequence of PGC-1 and wherein said mutation is associated with type 2 diabetes.
- 2. A polynucleotide according to claim 1, wherein said wild-type sequence encoding PGC-1 is the sequence of SEQ ID NO: 1.
- 3. A polynucleotide according to claim 1, where said mutation gives rise to at least one amino acid substitution in the PGC-1 polypeptide relative to the amino acid sequence of wild-type PGC-1.
- 4. A polynucleotide according to claim 3, wherein said mutation gives rise to a substitution of Gly to an amino acid different from Gly in the position corresponding to position 482 of the amino acid sequence of SEQ ID NO: 2.
- 5. A polynucleotide according to claim 3, wherein said mutation gives rise to a substitution of Gly to Ser in the position corresponding to position 482 of the amino acid sequence of SEQ ID NO: 2.
- 6. A polynucleotide according to claim 1, wherein said mutation corresponds to a mutation of G in position 1564 in SEQ ID NO: 1 to A.
- 7. A polynucleotide according to claim 1, wherein said polynucleotide is a DNA construct.
- 8. A recombinant vector comprising a polynucleotide according to claim 1.
- 9. A cell line or a transgenic non-human mammal comprising a polynucleotide according to claim 1.
- 10. A cell line according to claim 9, wherein the cell line is a mammalian cell line.
- 11. A method of detecting the presence of a mutation in a gene encoding PGC-1, the method comprising (i) obtaining a biological sample from a subject and (ii) analysing the sample for a mutation of at least one nucleotide in the PGC-1 sequence, wherein said mutation is associated with type 2 diabetes.
- 12. A method according to claim 11, wherein the mutation gives rise to at least one amino acid substitution in PGC-1.
- 13. A method according to claim 12, wherein the mutation gives rise to a substitution of Gly to an amino acid different from Gly in the position corresponding to position 482 of the amino acid sequence of SEQ ID NO: 2.
- 14. A method according to claim 13, wherein the mutation gives rise to a substitution of Gly to Ser in the position corresponding to position 482 of the amino acid sequence of SEQ ID NO: 2.
- 15. A method according to claim 11, wherein the mutation corresponds to a mutation of G in position 1564 in SEQ ID NO: 1 to A.
- 16. A method according to claim 11, wherein said analysing comprises: (i) isolating DNA from the sample, (ii) amplifying the DNA and (iii) hybridising the amplified DNA to a labelled polynucleotide comprising a nucleotide sequence encoding PGC-1 or a fragment thereof, wherein said polynucleotide comprises a mutation associated with type 2 diabetes of at least one nucleotide, and (iv) determining hybridisation of the labelled polynucleotide to the amplified DNA.
- 17. A method according to claim 16, wherein the labelled polynucleotide comprises (i) a nucleotide sequence as shown in the Sequence Listing as SEQ ID NO: 1 containing a mutation associated with type 2 diabetes of at least one nucleotide or (ii) a fragment of the nucleotide sequence shown in the Sequence Listing as SEQ ID NO: 1 including said mutation.
- 18. A method according to claim 16, wherein the mutation gives rise to at least one amino acid substitution in PGC-1.
- 19. A method according to claim 16, wherein the mutation gives rise to a substitution of Gly to an amino acid different from Gly in the position corresponding to position 482 of the amino acid sequence of SEQ ID NO: 2.
- 20. A method according to claim 16, wherein the mutation gives rise to a substitution of Gly to Ser in the position corresponding to position 482 of the amino acid sequence of SEQ ID NO: 2.
- 21. A method according to 16, wherein the mutation corresponds to a mutation of G in position 1564 in SEQ ID NO: 1 to A.
- 22. A method according to claim 16, wherein said labelled polynucleotide is a DNA construct.
- 23. A method according to claim 16, further comprising hybridising the amplified DNA to a second labelled polynucleotide, wherein said second polynucleotide comprises a DNA sequence corresponding to at least part of the wild-type gene encoding PGC-1, and determining hybridisation of said second labelled polynucleotide to the amplified DNA.
- 24. A method according to claim 23, wherein the label substance with which the labelled polynucleotide carrying the mutation is labelled is different from the label substance with which the second labelled polynucleotide corresponding to at least part of the wild-type DNA is labelled.
- 25. A method according to claim 11, wherein said method identifies predisposition to type 2 diabetes in a subject.
- 26. A diagnostic composition for determining predisposition to type 2 diabetes in a subject, the composition comprising a polynucleotide according to claim 1.
- 27. A diagnostic composition for detecting the presence of a mutation in the gene encoding PGC-1, the composition comprising a polynucleotide according to claim 1.
- 28. A test kit for detecting the presence of a mutation associated with type 2 diabetes in the gene encoding PGC-1, the kit comprising
(a) a first polynucleotide comprising a nucleotide sequence corresponding to at least part of the gene encoding PGC-1 and containing a mutation of at least one nucleotide, which mutation corresponds to the mutation the presence of which in the gene encoding PGC-1 is to be detected and, optionally (b) a second polynucleotide comprising a nucleotide sequence corresponding to at least part of the wild-type gene encoding PGC-1, and/or optionally (c) a restriction endonuclease, which cleaves PGC-1-encoding DNA at the site of the mutation.
- 29. A test kit according to claim 28, wherein the first polynucleotide is a polynucleotide.
- 30. A test kit according to claim 28, further comprising a means for amplifying DNA.
- 31. A test kit for detecting the presence of a mutation associated with type 2 diabetes in the gene encoding PGC-1, the kit comprising
(a) means for amplifying DNA, and (b) a labelled polynucleotide comprising a nucleotide sequence corresponding to at least part of the gene encoding PGC-1 and containing a mutation of at least one nucleotide, which mutation corresponds to the mutation the presence of which in the gene encoding PGC-1 is to be detected.
- 32. A test kit according to claim 31, wherein the labelled polynucleotide comprises a polynucleotide.
- 33. A test kit according to claim 31, which comprises a second labelled polynucleotide comprising a nucleotide sequence corresponding to at least part of the wild-type gene encoding PGC-1.
- 34. A test kit according to claim 33, wherein the label substance with which the labelled polynucleotide carrying the mutation is labelled is different from the label substance with which the second labelled polynucleotide corresponding to at least part of the wild-type DNA is labelled.
- 35. A test kit according to claim 33, wherein the second labelled polynucleotide is a DNA construct.
- 36. A test kit suitable for use in a method according to any of claims 11 to 25.
- 37. A test kit according to any of claims 28 to 36 for determining predisposition to type 2 diabetes in a subject.
- 38. An isolated polypeptide encoded by a polynucleotide according to claim 3.
- 39. An isolated polypeptide selected from the group consisting of
(a) a polypeptide having an amino acid sequence which is substantially homologous to residues 1 to 798 of SEQ ID NO: 2; (b) a polypeptide which is encoded by a polynucleotide comprising a nucleic acid sequence which hybridizes under low stringency conditions with (i) nucleotides 121 to 2514 of SEQ ID NO: 1 or (ii) a subsequence of (i) of at least 100 nucleotides, (c) a variant of a polypeptide comprising an amino acid sequence of SEQ ID NO: 2 comprising a substitution, deletion, and/or insertion of one or more amino acids; (d) an allelic variant of (a) or (b); and (e) a fragment of (a), (b), (c) or (d). wherein said isolated polypeptide is a variant of PGC-1 carrying an amino acid substitution associated with type 2 diabetes
Priority Claims (2)
Number |
Date |
Country |
Kind |
PA 2001 01080 |
Jul 2001 |
DK |
|
EP 01610061.2 |
Jun 2001 |
EP |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. 119 of Danish application no. PA 2001 01080 filed on Jul. 10, 2001, U.S. provisional application Ser. No. 60/296,920 filed on Jun. 8, 2001, U.S. provisional application no. 60/304,378 filed on Jul. 10, 2001, and European application no. EP 01610061.2 filed on Jun. 8, 2001, the contents of which are fully incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60296920 |
Jun 2001 |
US |
|
60304378 |
Jul 2001 |
US |