人类基因组中单倍型块的结构。

The structure of haplotype blocks in the human genome.

作者信息

Gabriel Stacey B, Schaffner Stephen F, Nguyen Huy, Moore Jamie M, Roy Jessica, Blumenstiel Brendan, Higgins John, DeFelice Matthew, Lochner Amy, Faggart Maura, Liu-Cordero Shau Neen, Rotimi Charles, Adeyemo Adebowale, Cooper Richard, Ward Ryk, Lander Eric S, Daly Mark J, Altshuler David

机构信息

Whitehead/MIT Center for Genome Research, Cambridge, MA 02139, USA.

出版信息

Science. 2002 Jun 21;296(5576):2225-9. doi: 10.1126/science.1069424. Epub 2002 May 23.

Abstract

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.

摘要

基于单倍型的方法为疾病基因定位提供了一种强有力的途径,该方法基于因果突变与其出现时的祖先单倍型之间的关联。作为国际人类基因组单体型图计划等位基因频率项目的一部分,我们对来自非洲、欧洲和亚洲的样本中51个常染色体区域(跨越人类基因组的1300万个碱基对)的单倍型模式进行了特征分析。我们发现,人类基因组可以被客观地解析为单倍型块:即相当大的区域,在这些区域几乎没有历史重组的证据,并且在这些区域内只观察到少数常见的单倍型。块的边界及其所包含的特定单倍型在不同人群中高度相关。我们证明,这样的单倍型框架在每个区域的常见基因变异关联研究中提供了强大的统计能力。我们的结果为构建人类基因组单倍型图谱奠定了基础,有助于对人类疾病进行全面的基因关联研究。

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