IDENTIFYING NIDDM GENES USING ADMIXED POPULATIONS

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from investigator's abstract) Several common chronic
diseases demonstrate prevalence differences among ethnically classified
groups For example, non-insulin dependent diabetes mellitus (NIDDM) is
2-fold to 10-fold more frequent in Hispanic and Amerindian populations than
in European and European-American populations; hypertension is more common
among African Americans; and obesity has a higher frequency in Hispanics and
Amerindians. These diseases are difficult to study using family-based
linkage techniques, primarily because of age-dependent onset and
interactions between genes and environmental exposures. A new method for
disease gene mapping using the linkage disequilibrium created when
ethnically distinct populations hybridize is well suited to the study of
common disease in hybrid populations like the U.S. African Americans and
Hispanic Americans. When populations admix, allelic associations are formed
at loci that have marked differences in allele frequency. The magnitude of
this admixture linkage disequilibrium (ALD) is proportional to the allele
frequency differential (delta) between the parental populations. Allelic
associations between unlinked loci quickly decay in 3 to generations.
Closely spaced loci, however, will remain in non-random association for many
generations; the length of time and the magnitude of the linkage
disequilibrium being dependent on the proximity of the loci and the delta
levels between the parental populations. Using this approach, it will thus
be possible to detect genetic linkage between polymorphic markers and
disease susceptibility loci by way of associations observed in cases and
controls. The investigators have performed extensive computer simulation
studies on the dynamics of linkage disequilibrium in admixed populations.
This work has shown that there will be significant statistical power to
detect disease genes using mapping by ALD. This is especially true for
testing the importance of candidate genes and candidate regions. They
propose to test 40 candidate genes and regions for linkage to NIDDM in a
well-characterized population of Hispanics living in the San Luis Valley of
Colorado. They will verify any positive associations found using sib-pair
linkage analysis and the transmission disequilibrium test.
StatusFinished
Effective start/end date9/30/9812/31/98

Funding

  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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