Linkage disequilibrium in humans: Models and data

In this review, we describe recent empirical and theoretical work on the ex tent of linkage disequilibrium (LD) in the human genome, comparing the pred ictions of simple population-genetic models to available data. Several stud ies report significant LD over distances longer than those predicted by sta ndard models, whereas some data from short, intergenic regions show less LD than would be expected. The apparent discrepancies between theory and data present a challenge-both to modelers and to human geneticists-to identify which important features are missing from our understanding of the biologic al processes that give rise to LD. Salient features may include demographic complications such as recent admixture, as well as genetic factors such as local variation in recombination rates, gene conversion, and the potential segregation of inversions. We also outline some implications that the emer ging patterns of LD have for association-mapping strategies. In particular, we discuss what marker densities might be necessary for genomewide associa tion scans.