人群隔离群体中连锁不平衡的程度与分布及其对全基因组关联研究的意义

Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies.

作者信息

Service Susan, DeYoung Joseph, Karayiorgou Maria, Roos J Louw, Pretorious Herman, Bedoya Gabriel, Ospina Jorge, Ruiz-Linares Andres, Macedo António, Palha Joana Almeida, Heutink Peter, Aulchenko Yurii, Oostra Ben, van Duijn Cornelia, Jarvelin Marjo-Riitta, Varilo Teppo, Peddle Lynette, Rahman Proton, Piras Giovanna, Monne Maria, Murray Sarah, Galver Luana, Peltonen Leena, Sabatti Chiara, Collins Andrew, Freimer Nelson

机构信息

Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA.

出版信息

Nat Genet. 2006 May;38(5):556-60. doi: 10.1038/ng1770. Epub 2006 Apr 2.

DOI:10.1038/ng1770

PMID:16582909

Abstract

The genome-wide distribution of linkage disequilibrium (LD) determines the strategy for selecting markers for association studies, but it varies between populations. We assayed LD in large samples (200 individuals) from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22. Most isolates show substantially higher levels of LD than the outbred sample and many fewer regions of very low LD (termed 'holes'). Young isolates known to have had relatively few founders show particularly extensive LD with very few holes; these populations offer substantial advantages for genome-wide association mapping.

摘要

连锁不平衡（LD）的全基因组分布决定了关联研究中选择标记的策略，但其在不同人群中存在差异。我们使用分布于22号染色体上的单核苷酸多态性（SNP）标记，对11个详细描述的人群隔离群中的每个群体的大样本（200人）以及一个欧洲裔非隔离群样本进行了LD检测。大多数隔离群显示出比非隔离群样本更高的LD水平，且极低LD（称为“空洞”）的区域要少得多。已知奠基者相对较少的年轻隔离群显示出特别广泛的LD，空洞极少；这些群体在全基因组关联图谱绘制方面具有显著优势。