INVESTIGATIONS OF GENETIC DISEQUILIBRIA AS GENE MAPPING STRATEGIES

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Our research has focussed on developing a gene mapping strategy that capitalizes on linkage disequilibrium in recently admixed populations. It is a reasonably well-known population genetic phenomenon that populations formed by recent admixture of genetically divergent populations will harbor greatly elevated levels of linkage disequilibrium. However, the disequilibrium will exist between unlinked genes as well as linked genes. The latter observation suggests that any strategy that makes use of the disequilibrium as an indication of linkage will need to be optimized to discriminate between these two possibilities. In the course of developing our strategy (named MALD--mapping by admixture linkage disequilibrium), we have used a variety of mathematical and computer simulation approaches to identify parameters having the greatest influence on detectability of linkage disequilibrium. In particular, we ascertained values of each parameter that would allow efficient gene mapping, in concert with two proposed strategies for declaring linkage. Furthermore, we have constructed a polymorphic admixture typing map (PATMAP) of 257 genetic markers. These markers were scored on population samples of Caucasians, African-Americans, Asians (Chinese), and Amerindians (Cheyenne). A substantial proportion of the markers had large gene frequency differences between populations, confirming their relevance to the MALD approach.