Methods of diagnosis

• US 20060234274A1
• Filed: 03/29/2006
• Published: 10/19/2006
• Est. Priority Date: 03/29/2005
• Status: Abandoned Application

• Current Assignee: Auckland UniServices Limited (Auckland University)
• Original Assignee: Auckland UniServices Limited (Auckland University)
• Inventors: Shelling, Andrew Neil, Harris, Sarah Elizabeth
• Application Number:
  US11/391,736
• Publication Number:
  US 20060234274A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6888 for detection or identification of organisms
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

A method to detect whether a female subject is predisposed to POF, the method comprising analysing at least one or more polymorphism in the INHA gene chosen from the group consisting: −124A>G; −16C>T; TG repeat (as herein after described); and one or more polymorphism in the INHA gene which is in linkage disequilibrium with one or more of −124A>G, −16C>T or TG repeat (as herein after described).

Claims

1. A method to detect whether a female subject is predisposed to POF, the method comprising analysing at least one or more polymorphism in the INHA gene chosen from the group consisting:

−

1 24A>

G;

−

16C>

T;

TG repeat (as herein after described); and

One or more polymorphism in the INHA gene which is in linkage disequilibrium with one or more of −

124A>

G, −

16C>

T or TG repeat (as herein after described).

4. A method as claimed in claim 1 wherein the one or more polymorphism in the INHA gene which is in linkage disequilibrium is 531C>

T.

8. A method as claimed in claim 1 wherein heterozygosity or homozygosity for haplotype C (as herein after described) of the TG repeat is indicative of protection against POF.

9. A method as claimed in claim 1 wherein heterozygosity or homozygosity for −

16T (the T allele) is indicative of protection against POF.

10. A method as claimed in claim 1 wherein homozygosity for −

124A is indicative of susceptibility or predisposition to POF, and predictive of potential onset of infertility.

11. A method as claimed in claim 1 wherein homozygosity or heterozygosity for −

124G is indicative of protection against POF.

12. A method as claimed in claim 1 wherein analysis of one or more polymorphisms occurs via analysis of DNA encoding INHA.

13. A method as claimed in claim 1 wherein where a polymoprhism in linkage disequillibrium is analysed and said polymorphism is located in a coding region, the method involves analysis of RNA encoding INHA.

14. A method as claimed in claim 12 or 13 wherein analysis of one or more polymorphisms occurs using one or more of:

polymerase chain reaction (PCR);

gel electrophoresis;

Southern blotting;

Nucleic acid sequencing;

restriction fragment length polymorphism (RFLP);

single-strand confirmation polymphism (SSCP);

LCR (ligase chain reaction);

denaturing gradient gel electrophoresis (DGGE);

allele-specific oligonucleotides (ASOs);

proteins which recognize nucleic acid mismatches;

RNAse protection;

oligo array hybridisation;

denaturing HPLC (dHPLC); and

, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS).

2. A method for diagnosing POF in a female subject, the method comprising analysing at least one or more polymorphism in the INHA gene chosen from the group consisting:

−

124A>

G;

−

16C>

T;

TG repeat (as herein after described); and

,

One or more polymorphism in the INHA gene which is in linkage disequilibrium with one ore more of −

124A>

G, −

16C>

T or TG repeat (as herein after described).

3. A method for predicting the onset of infertility in a female subject, the method comprising at least the analysis of one or more polymorphism in the INHA gene chosen from the group consisting:

−

124A>

G;

−

16C>

T;

TG repeat (as herein after described); and

One or more polymorphism in the INHA gene which is in linkage disequilibrium with one or more of −

124A>

G, −

16C>

T or TG repeat (as herein after described).

5. A method to detect whether a female subject is predisposed to POF, the method comprising determining the subjects genotype in respect of a TG repeat polymorphism (as herein after described) in the INHA gene by analysing one or more of the polymorphisms chosen from the group consisting:

−

16C>

T; and

,

−

124A>

G.

6. A method for diagnosing POF in a female subject, the method comprising determining the subjects genotype in respect of a TG repeat polymorphism (as herein after described) in the INHA gene by analysing one or more of the polymorphisms chosen from the group consisting:

−

16C>

T; and

,

−

124A>

G.

7. A method for predicting the onset of infertility in a female subject, the method comprising determining the subjects genotype in respect of a TG repeat polymorphism (as herein after described) in the INHA gene by analysing one or more of the polymorphisms chosen from the group consisting:

−

16C>

T; and

,

−

124A>

G.