Repeat polymorphism in the frataxin gene and uses therefore

• US 6,322,978 B1
• Filed: 04/15/1999
• Issued: 11/27/2001
• Est. Priority Date: 04/20/1998
• Status: Expired due to Fees

• Current Assignee: Joslin Diabetes Center Inc.
• Original Assignee: Joslin Diabetes Center Inc.
• Inventors: Kahn, C. Ronald, Ristow, Michael
• Primary Examiner(s): Schwartzman, Robert A.
• Assistant Examiner(s): LI, QIAN JANICE
• Application Number:
  US09/292,487
• Time in Patent Office: 957 Days
• Field of Search: 435/6, 563/24.31, 536/24.31, 536/24.33
• US Class Current: 435/6.16
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers

Abstract

The invention provides methods of determining whether a subject is at risk for a disorder characterized by an intermediate GAA repeat length polymorphism in the frataxin gene.

Claims

1. A method for determining whether a human subject is at risk for non-insulin dependent diabetes mellitus (NIDDM) comprising:

obtaining a biological sample from said subject; and

detecting the presence or absence of an intermediate GAA repeat length polymorphism of 10 to 36 repeats in a frataxin gene in said biological sample, wherein the presence of an intermediate GAA repeat length polymorphism of 10 to 36 repeats in the frataxin gene indicates higher risk for NIDDM than does the absence of the polymorphism,

thereby determining whether said subject is at risk for NIDDM.

2. The method of claim 1, further comprising isolating a nucleic acid molecule from said biological sample.

3. The method of claim 2, wherein said nucleic acid molecule is DNA.

4. The method of claim 1, wherein the presence or absence of an intermediate GAA repeat length polymorphism in the frataxin gene is detected by the use of a polymerase chain reaction.

5. The method of claim 1, wherein the presence or absence of an intermediate GAA repeat length polymorphism in the frataxin gene is detected by an alteration in a restriction enzyme cleavage pattern.

6. The method of claim 1, wherein the presence or absence of an intermediate GAA repeat length polymorphism in the frataxin gene is detected by nucleic acid sequencing.

7. The method of claim 1, wherein said biological sample is a biological fluid.

8. The method of claim 1, wherein said biological sample is a tissue sample.

9. The method of claim 1, wherein said biological sample is a cellular sample.

10. A method for determining whether a human subject is at risk for non-insulin dependent diabetes mellitus (NIDDM), comprising a DNA sample from the human subject with a nucleic acid probe, and detecting a frataxin intermediate GAA repeat length polymorphism of 10 to 36 repeats in the DNA sample, wherein the presence of an intermediate GAA repeat length polymorphism of 10 to 36 repeats in the frataxin gene indicates higher risk for NIDDM than dose the absence of the polymorphism, thereby determining if the subject is at risk for NIDDM.

11. The method of claim 10, wherein the nucleic acid probe is a labeled or unlabelled nucleic acid probe that hybridizes to frataxin DNA.

12. The method of claim 10, wherein the nucleic acid probe is a nucleic acid probe that amplifies a frataxin gene containing an intermediate length GAA repeat.

13. A kit for determining whether a human subject is at risk for non insulin dependent diabetes mellitus (NIDDM), comprising a nucleic acid probe that detects a frataxin intermediate GAA repeat length polymorphism of 10 to 36 repeats in a nucleic acid sample, and instructions for using the kit to determine if a subject is at risk for NIDDM.

14. The kit of claim 13, further comprising means for determining the amount of a frataxin intermediate GAA repeat length polymorphism in the sample and means for comparing the amount of a frataxin intermediate GAA repeat length polymorphism in the sample with a standard.

15. The kit of claim 13, wherein the nucleic acid probe is a labeled or unlabelable nucleic acid probe that hybridizes to frataxin DNA.

16. The kit of claim 13, wherein the nucleic acid probe is a nucleic acid probe that amplifies a frataxin gene containing an intermediate length GAA repeat.