Population-specific recombination sites within the human MHC region
Population-specific recombination sites within the human MHC region
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DOI：
10.1038/hdy.2013.27
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发表时间：
2013-08-01
期刊：
影响因子：
3.8
通讯作者：
Ren, E. C.
中科院分区：
文献类型：
--
作者：
Lam, T. H.;Shen, M.;Ren, E. C.
通过重组进行的基因重排是基因组进化的主要驱动力之一，并且已知重组发生在基因组内非随机、离散的重组位点。重组位点的定位已被证明是困难的，特别是在人类MHC区域，这是由群体变异和高度多态性的HLA基因复杂的。为了克服这些问题，来自亚洲、欧洲和非洲三个代表性人群的HLA型个体被用于生成分阶段HLA单倍型。从分阶段单倍型数据构建的扩展单倍型纯合性（EHH）图显示，重组事件对应的EHH离散下降，并且观察到这些特征在每个群体中是不同的。令人惊讶的是，检测到的大多数重组位点对每个种群都是独特的，而不是普遍的。独特重组位点在亚洲人群中占56.8%（占总位点的21/37），在欧洲人群中占50.0%(15/30)，在非洲人群中占63.2%（24/38）。在已知的45 kb （hla - f端粒）的精子分型重组位点进行验证，结果表明EHH是一种有效的方法，可以将重组区域缩小到826 bp，通过重测序进一步将重组区域缩小到660 bp。这种方法显著增强了人类MHC基因组结构的图谱，并将在识别疾病风险基因的研究中发挥作用。
Genetic rearrangement by recombination is one of the major driving forces for genome evolution, and recombination is known to occur in non-random, discreet recombination sites within the genome. Mapping of recombination sites has proved to be difficult, particularly, in the human MHC region that is complicated by both population variation and highly polymorphic HLA genes. To overcome these problems, HLA-typed individuals from three representative populations: Asian, European and African were used to generate phased HLA haplotypes. Extended haplotype homozygosity (EHH) plots constructed from the phased haplotype data revealed discreet EHH drops corresponding to recombination events and these signatures were observed to be different for each population. Surprisingly, the majority of recombination sites detected are unique to each population, rather than being common. Unique recombination sites account for 56.8% (21/37 of total sites) in the Asian cohort, 50.0% (15/30 sites) in Europeans and 63.2% (24/38 sites) in Africans. Validation carried out at a known sperm typing recombination site of 45 kb (HLA-F-telomeric) showed that EHH was an efficient method to narrow the recombination region to 826 bp, and this was further refined to 660 bp by resequencing. This approach significantly enhanced mapping of the genomic architecture within the human MHC, and will be useful in studies to identify disease risk genes.