Population-specific recombination sites within the human MHC region

Genetic rearrangement by recombination is one of the major driving forces for genomeevolution, and recombination is known to occur in non-random, discreet recombination siteswithin the genome. Mapping of recombination sites has proved to be difficult,particularly, in the human MHC region that is complicated by both population variation andhighly polymorphic HLA genes. To overcome these problems, HLA-typed individualsfrom three representative populations: Asian, European and African were used to generatephased HLA haplotypes. Extended haplotype homozygosity (EHH) plots constructed from thephased haplotype data revealed discreet EHH drops corresponding to recombination eventsand these signatures were observed to be different for each population. Surprisingly, themajority of recombination sites detected are unique to each population, rather than beingcommon. Unique recombination sites account for 56.8% (21/37 of total sites) inthe Asian cohort, 50.0% (15/30 sites) in Europeans and 63.2% (24/38sites) in Africans. Validation carried out at a known sperm typing recombination site of45 kb (HLA-F-telomeric) showed that EHH was an efficient method to narrowthe recombination region to 826 bp, and this was further refined to 660 bpby resequencing. This approach significantly enhanced mapping of the genomic architecturewithin the human MHC, and will be useful in studies to identify disease risk genes.