Human recombination hot spots hidden within regions of strong marker association

Abstract

The fine-scale distribution of meiotic recombination events in the human genome can be inferred from patterns of haplotype diversity in human populations but only directly studied by high-resolution sperm typing. Both approaches indicate that crossovers are heavily clustered into narrow recombination hot spots. However, our direct understanding of hot-spot properties and distributions is largely limited to sperm typing in the major histocompatibility complex (MHC). We now describe the analysis of an unremarkable 206 kb region on human chromosome 1, revealing localised regions of linkage disequilibrium (LD) breakdown that mark the locations of sperm crossover hot spots. The distribution, intensity and morphology of these hot spots are strikingly similar to those in the MHC. However, we also accidentally detected additional hot spots within regions of strong association. Coalescent analysis of genotype data detected most of the hot spots, but revealed significant differences between sperm crossover frequencies and “historical” recombination rates. This raises the possibility that some hot spots, in particular those in regions of strong association, may have evolved very recently and not left their full imprint on haplotype diversity. These results suggest that hot spots could be very abundant and possibly fluid features of the human genome