The structure of haplotype blocks in the human genome
The structure of haplotype blocks in the human genome
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DOI：
10.1126/science.1069424
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发表时间：
2002-06-21
期刊：
影响因子：
56.9
通讯作者：
Altshuler, D
中科院分区：
文献类型：
--
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
基于单倍型的方法提供了一个强大的方法来疾病基因定位，基于因果突变和祖先单倍型之间的关联，他们出现。作为SNP联盟等位基因频率项目的一部分，我们在来自非洲、欧洲和亚洲的样本中描述了51个常染色体区域（跨越13兆人类基因组）的单倍型模式。我们表明，人类基因组可以被客观地解析成单倍型块：相当大的区域，几乎没有证据表明历史重组，只有少数常见的单倍型被观察到。块的边界和它们所包含的特定单倍型在种群间高度相关。我们证明，这样的单倍型框架提供了大量的统计权力，在每个地区的共同遗传变异的关联研究。我们的研究结果为构建人类基因组单倍型图谱奠定了基础，促进了人类疾病的全面遗传关联研究。
Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed. The boundaries of blocks and specific haplotypes they contain are highly correlated across populations. We demonstrate that such haplotype frameworks provide substantial statistical power in association studies of common genetic variation across each region. Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease.