Recombination hotspots rather than population history dominate linkage disequilibrium in the MHC class II region

被引:87
作者
Kauppi, L
Sajantila, A
Jeffreys, AJ
机构
[1] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England
[2] Univ Helsinki, Dept Forens Med, SF-00300 Helsinki, Finland
基金
英国医学研究理事会;
关键词
D O I
10.1093/hmg/ddg008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recombination, demographic history, drift and selection influence the extent of linkage disequilibrium (LD) in the human genome, but their relative contributions remain unclear. To investigate the effect of meiotic recombination versus population history on LD, three populations with different demographic histories (UK north Europeans, Saami and Zimbabweans) were genotyped for high-frequency single-nucleotide polymorphisms (SNPs) across a 75 kb DNA segment of the MHC class II region. This region spans three well-characterized recombination hotspots and a 60 kb long LD block. Despite a high level of Underlying haplotype diversity and considerable divergence in haplotype composition between populations, all three populations showed very similar patterns of LD. Surprisingly, the entire 60 kb LD block was present even in Africans, although it was relatively difficult to detect owing to a systematic deficiency of high, frequency SNPs. In contrast, DNA within recombination hotspots did not show this low nucleotide diversity in Africans. Thus, while population history has some influence on LD, our findings suggest that recombination hotspots play a major global role in shaping LD patterns as well as helping to maintain localized SNP diversity in this region of the MHC.
引用
收藏
页码:33 / 40
页数:8
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