Coriell Institute for Medical Research, Camden, New Jersey, United States of America.
PLoS One. 2010 Oct 15;5(10):e13443. doi: 10.1371/journal.pone.0013443.
Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification.
METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (F(st)), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race.
CONCLUSION/SIGNIFICANCE: CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions.
遗传血统已知会影响旨在确定人类群体常见疾病风险的基因型 - 表型研究的结果。由于遗传血统而未能控制人口分层，可能会严重混淆疾病关联研究的结果。此外，血统是评估疾病终身风险的关键因素，并且可以在优化治疗方面发挥重要作用。随着现代医学朝着将个人遗传信息用于临床应用的方向发展，以准确、具有成本效益和高效的方式确定遗传血统非常重要。自我认同的种族是用于跟踪和控制人口分层的常用方法；然而，种族的社会结构对于遗传应用不一定具有信息性。使用遗传血统信息标记（AIMs）是一种更准确的方法，可用于确定人口分层的遗传血统。
方法/主要发现：在这里，我们介绍了一组 36 个微卫星（MSAT）AIMs，用于确定大陆混合比例。这个面板，我们称之为大陆遗传血统信息标记或 CoAIMs，由基于其遗传方差（F（st））、等位基因频率及其适用于高效基因分型的 MSAT AIMs 组成。使用 CoAIMs 进行基因型分析以及贝叶斯聚类方法（STRUCTURE）能够辨别出大陆起源，包括欧洲/中东（高加索人）、东亚、非洲、美洲原住民和大洋洲。除了确定没有明显混合的个体的大陆血统外，我们还应用 CoAIMs 确定自我宣称种族的个体的混合比例。
结论/意义：CoAIMs 可用于高效，有效地确定样本集中的大陆混合比例。CoAIMs 面板是遗传研究人员进行病例对照遗传关联研究的宝贵资源，因为它可以控制人口分层的混杂影响。这里使用的基于 MSAT 的方法具有广泛适用性的潜力，是一种经济有效的确定混合比例的工具。
