BACKGROUND:The study of genetic variation will promote our understanding of the differential predisposition to common diseases and variation in drug responses of individuals and ethnic populations. Such genetic variation is intrinsically structured into blocks of haplotypes in populations. Therefore, a comprehensive haplotype map based on the most abundant form of genetic variation, single nucleotide polymorphisms, will be useful. At the present time, however, our knowledge of the similarities and differences of haplotype structure among different ancestral populations is still inadequate. METHODS:To determine whether common underlying haplotype patterns existed across ethnic populations, we analyzed data derived from African and European Americans for twenty-two genes spanning a total of 516 kb and the HapMap ENCODE data across 500 kb on chromosome 2p16.3 from three major world populations. RESULTS AND CONCLUSIONS:We observed that strong pairwise linkage disequilibrium (LD) between SNPs selected from populations having African ancestry was highly conserved across other non-African populations. Common haplotypes described by these LD-selected SNPs demonstrated a simple evolutionary structure with up to three major frameworks, which were likely ancestral backgrounds upon which more recent mutations have been superimposed. Also, haplotype block boundaries defined in populations having African ancestry revealed completely concordant recombinant haplotypes across all populations, providing a consistent definition of block structure. Finally, a large fraction of regulatory polymorphisms described in the literature appeared to tag these conserved haplotype frameworks, strongly suggesting their significance for disease association and pharmacogenetic studies.

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背景:遗传变异的研究将促进我们对常见疾病的不同易感性以及个体和种族的药物反应变异的了解。这样的遗传变异本质上被构造成种群中单倍型的块。因此,基于遗传变异的最丰富形式,即单核苷酸多态性的综合单倍型图将很有用。然而,目前,我们对不同祖先群体单倍型结构的异同的认识仍然不足。
方法:为确定族群之间是否存在常见的潜在单倍型模式,我们分析了来自非洲和欧洲裔的22个基因的数据,这些基因跨度共516 kb,而HapMap ENCODE数据涉及3个主要染色体2p16.3上的500 kb世界人口。
结果与结论:我们观察到,从具有非洲血统的人群中选出的SNP之间的强烈成对连锁不平衡(LD)在其他非非洲人群中都得到了高度保守。这些由LD选择的SNP描述的常见单倍型显示出具有多达三个主要框架的简单进化结构,这可能是祖先的背景,在这些背景上已叠加了更多的近期突变。同样,在具有非洲血统的种群中定义的单倍型块边界揭示了所有种群中完全一致的重组单倍型,从而提供了一致的块状结构定义。最后,文献中描述的大部分调控多态性似乎标记了这些保守的单倍型框架,强烈暗示了它们对疾病关联和药物遗传学研究的重要性。

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