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.
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