Significant admixture linkage disequilibrium across 30 cM around the FY locus in African Americans

Scientists, to understand the importance of allelic polymorphisms on phenot ypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigr ee analysis is difficult. Because association screens require linkage diseq uilibrium between markers and disease loci, maximizing the degree of linkag e disequilibrium increases the chances of discovering functional gene-marke r associations. One theoretically valid approach-mapping by admixture linka ge disequilibrium (MALD), using recently admired African Americans-is empir ically evaluated here by measurement of marker associations with 15 short t andem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locu s in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymo rphism ( - 46T->C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of EY - / - in malaria infections. Analysis of li nkage disequilibrium around the EY gene has indicated that there is strong and consistent linkage disequilibrium between EY and three nanking loci (D1 S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-dis equilibrium signals over a 30-cM region from -4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estim ates of centimorgan limits, by MALD assessment in African American populati on-association analyses, of 5-10 cM.