利用基因组扫描标记对高血压基因座进行混合映射。

Admixture mapping for hypertension loci with genome-scan markers.

作者信息

Zhu Xiaofeng, Luke Amy, Cooper Richard S, Quertermous Tom, Hanis Craig, Mosley Tom, Gu C Charles, Tang Hua, Rao Dabeeru C, Risch Neil, Weder Alan

机构信息

Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, 2160 S. First Ave., Maywood, Illinois 60153, USA.

出版信息

Nat Genet. 2005 Feb;37(2):177-81. doi: 10.1038/ng1510. Epub 2005 Jan 23.

Abstract

Identification of genetic variants that contribute to risk of hypertension is challenging. As a complement to linkage and candidate gene association studies, we carried out admixture mapping using genome-scan microsatellite markers among the African American participants in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program. This population was assumed to have experienced recent admixture from ancestral groups originating in Africa and Europe. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and used the European Americans in the Family Blood Pressure Program to provide estimates of allele frequencies for the European ancestors. We genotyped a common set of 269 microsatellite markers in the three groups at the same laboratory. The distribution of marker location-specific African ancestry, based on multipoint analysis, was shifted upward in hypertensive cases versus normotensive controls, consistent with linkage to genes conferring susceptibility. This shift was largely due to a small number of loci, including five adjacent markers on chromosome 6q and two on chromosome 21q. These results suggest that chromosome 6q24 and 21q21 may contain genes influencing risk of hypertension in African Americans.

摘要

识别导致高血压风险的基因变异具有挑战性。作为连锁和候选基因关联研究的补充,我们在美国国立心肺血液研究所的家庭血压项目中的非裔美国参与者中,使用基因组扫描微卫星标记进行了混合映射。假定该人群近期经历了源自非洲和欧洲的祖先群体的混合。我们使用一组来自尼日利亚的无关个体来代表非洲祖先群体,并利用家庭血压项目中的欧裔美国人来估计欧洲祖先的等位基因频率。我们在同一实验室对三组中的一组共269个微卫星标记进行了基因分型。基于多点分析,标记位置特异性非洲血统在高血压病例中的分布相对于血压正常的对照向上偏移,这与赋予易感性的基因连锁一致。这种偏移主要归因于少数位点,包括6号染色体q臂上的五个相邻标记和21号染色体q臂上的两个标记。这些结果表明,6号染色体q24和21号染色体q21可能包含影响非裔美国人高血压风险的基因。

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