Novel susceptibility gene for late-onset NIDDM is localized to human chromosome 12q.

Abstract:

:NIDDM has a substantial genetic component, but the nature of the genetic susceptibility is largely unknown. Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of NIDDM characterized by an early age of onset and autosomal dominant inheritance, and linkage studies have identified genes that are mutated in different MODY pedigrees on chromosome 20 (MODY1 locus, hepatocyte nuclear factor-4alpha [HNF-4alpha] gene), chromosome 7 (MODY2 locus, glucokinase gene), and chromosome 12 (MODY3 locus, HNF-1alpha gene). We studied an extended pedigree in which multiple members are affected by late-onset NIDDM associated with insulin resistance and performed linkage analysis with four microsatellite markers in the MODY3 region of chromosome 12q. We found significant evidence for linkage between NIDDM and the MODY3 locus (logarithm of odds score 3.65 at theta = 0.008 telomeric to marker D12S321), but sequencing of the 10 exons and promoter of HNF-1alpha did not identify any causative mutation in this gene. Our results indicate that the region of chromosome 12q close to MODY3 harbors a novel susceptibility gene or genes for NIDDM.

journal_name

Diabetes

journal_title

Diabetes

authors

Shaw JT,Lovelock PK,Kesting JB,Cardinal J,Duffy D,Wainwright B,Cameron DP

doi

10.2337/diabetes.47.11.1793

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

1793-6

issue

11

eissn

0012-1797

issn

1939-327X

journal_volume

47

pub_type

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