Population structure in admired populations: Effect of admixture dynamics on the pattern of linkage disequilibrium

Gene now between genetically distinct populations creates linkage disequili brium (admixture linkage disequilibrium [ALD]) among all loci (linked and u nlinked) that have different allele frequencies in the founding populations , We have explored the distribution of ALD by using computer simulation of two extreme models of admixture: the hybrid-isolation (HI) model, in which admixture occurs in a single generation, and the continuous-gene-flow (CGF) model, in which admixture occurs at a steady rate in every generation. Lin kage disequilibrium patterns in African American population samples from Ja ckson, MS, and from coastal South Carolina resemble patterns observed in th e simulated CGF populations, in two respects. First, significant associatio n between two loci (FY and AT3) separated by 22 cM was detected in both sam ples. The retention of ALD over relatively large (>10 cM) chromosomal segme nts is characteristic of a CGF pattern of admixture but not of an HI patter n. Second, significant associations were also detected between many pairs o f unlinked loci, as observed in the CGF simulation results but not in the s imulated HI populations. Such a high rate of association between unlinked m arkers in these populations could result in false-positive linkage signals in an admixture-mapping study. However, we demonstrate that by conditioning on parental admixture, we can distinguish between true linkage and associa tion resulting from shared ancestry. Therefore, populations with a CGF hist ory of admixture not only are appropriate for admixture mapping but also ha ve greater power for detection of linkage disequilibrium over large chromos omal regions than do populations that have experienced a pattern of admixtu re more similar to the HI model, if methods are employed that detect and ad just for disequilibrium caused by continuous admixture.