Effects of worldwide population subdivision on ALDH2 linkage disequilibrium

The effect of human population subdivision on linkage disequilibrium has pr eviously been studied for unlinked genes. However, no study has focused on closely linked polymorphisms or formally partitioned linkage disequilibrium within and among worldwide populations. With an emphasis on population sub division, the goal of this paper is to investigate the causes of linkage di sequilibrium in ALDH2, the gene that encodes aldehyde dehydrogenase 2. Hapl otypes for 756 people from 17 populations across five continents were estim ated by maximum-likelihood From genotypes at six closely linked ALDH2, nucl eotide substitutions. Linkage disequilibrium was partitioned into three com ponents: within populations, among populations within continents, and among continents. It was Found that; population subdivision among continents had a larger and more disparate effect on linkage disequilibrium than subdivis ion among local populations. Further, linkage disequilibrium did not increa se with population divergence-as predicted by a simple model. Rather, the p atterns of linkage disequilibrium were complicated because of the interplay of a near absence of recombination, the linkage disequilibrium that existe d prior to the divergence of modern humans, subsequent mutation, population subdivision, random genetic drift, and perhaps natural selection. These re sults suggest that simple models may not well predict patterns of linkage d isequilibrium in human populations.