Understanding the importance of allelic polymorphisms on quantitative and environmentally interacting phenotypes is now turning to population association screens, especially in cases where pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chance of discovering functional gene- marker associations. One theoretically valid approach, mapping by admixture linkage disequilibrium (MALD) using recently admixed African Americans, is evaluated here empirically by measuring marker associations with 15 short tandem repeats (STRs) and an insertion/deletion (indel) polymorphism of the AT3 locus in a 70 cM segment at 1q22-23 around the FY (Duffy) locus. The FY polymorphism (- 46T-C) disrupts the GATA promoter motif specifically blocking FY erythroid expression and has a nearly fixed allele frequency difference between Caucasians and Africans which is likely a consequence of a selective advantage of FY -/- in malaria infections. Analysis of linkage disequilibrium around the FY gene revealed that three flanking loci (D1S303, SPTA1 and D1S484) spanning 8 cM showed strong and consistent linkage disequilibrium with FY. Significant linkage disequilibrium signals were observed over a 30 cM region from -4.4 to 16.3 cM (D1S2777 to D1S196) for STRs and at 26.4 cM (AT3) providing quantitative estimates of cM limits using MALD assessment in African American population association analyses of 5 to 10 cM. - admixture, Genetic epidemiology, linkage disequilibrium, - Human Tissues, Fluids, Cells, etc.
