Insights into recombination from patterns of linkage disequilibrium

Abstract

Recent studies of linkage disequilibrium (LD) have suggested that (1) recombination rates vary tremendously across the genome, such that large scale estimates of the recombination rate based on a comparison of physical and genetic maps may not be informative about local patterns of LD (2) models of recombination that include gene conversion as well as crossing-over better predict levels of LD at short scales (3) levels of LD are lower in samples from sub-Saharan African populations than in other population samples. These observations have important implications for linkage disequilibrium based association-studies; they suggest that large areas of the genome can be tagged with few markers, and that genome-wide studies and fine scale mapping efforts might best be conducted in different populations. To examine the generality of these observations, we analyzed over 80 data sets sequenced in 24 African-Americans and 23 individuals of European descent (data from http://pga. mbt. washington. edu/). As an index of LD, we estimated the population rate of crossing-over q in the two ?population? samples. We compared estimates of p (with and without gene conversion) to those obtained from a comparison of genetic and physical maps. To gain a sense of recombination rate variation at a small scale, we also considered how much estimates of p vary along sequences in actual data compared to simulated data.