Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel.
Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel.
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DOI：
10.1186/2041-2223-4-13
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发表时间：
2013-07-01
期刊：
影响因子：
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通讯作者：
Kidd JR
中科院分区：
文献类型：
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作者：
Nievergelt CM;Maihofer AX;Shekhtman T;Libiger O;Wang X;Kidd KK;Kidd JR
准确确定遗传祖先是高度感兴趣的许多领域，如生物医学研究，个人基因组学和法医学。它仍然是遗传关联研究中的一个重要课题，因为已经表明，如果不适当考虑群体分层，可能导致假阳性和假阴性结果。虽然大型关联研究通常从可用的全基因组SNP基因型中提取祖先信息，但在GWAS领域之前收集的关于罕见表型和历史集合的许多重要临床数据集需要一种可行的方法（即，易于基因分型，标记数量少）来推断研究对象的地理来源和潜在混合物。在这里，我们报告的发展，应用和局限性的一个小的，多功能的祖先信息标记（AIM）面板的SNP（或AISNP）专门为此目的而开发。基于来自HGDP的全球人群，选择了用于使用ABI SNPlex进行多重应用的41-AIM AISNP组和用于Sequenome iPLEX系统的具有31个AIM的子集，发现其对于推断七个大陆地区的血统具有高度信息性非洲、中东、欧洲、中亚/南亚、东亚、美洲和大洋洲。该小组被认为是欧亚人群的信息量最少，并建议增加更高分辨率的AIM。收集了一个大型参考集，包括从120个全球人群中收集的4,000多名受试者，以促进准确的祖先确定。我们展示了这个AIM面板的实际应用，讨论了它在混合个体中的局限性，并提出了将祖先信息纳入遗传关联研究的方法。我们展示了一个专门开发用于辨别全球血统的小型AISNP面板的实用性。我们相信，由于其可行性和广泛应用的潜力，它将得到广泛的应用。
Accurate determination of genetic ancestry is of high interest for many areas such as biomedical research, personal genomics and forensics. It remains an important topic in genetic association studies, as it has been shown that population stratification, if not appropriately considered, can lead to false-positive and -negative results. While large association studies typically extract ancestry information from available genome-wide SNP genotypes, many important clinical data sets on rare phenotypes and historical collections assembled before the GWAS area are in need of a feasible method (i.e., ease of genotyping, small number of markers) to infer the geographic origin and potential admixture of the study subjects. Here we report on the development, application and limitations of a small, multiplexable ancestry informative marker (AIM) panel of SNPs (or AISNP) developed specifically for this purpose. Based on worldwide populations from the HGDP, a 41-AIM AISNP panel for multiplex application with the ABI SNPlex and a subset with 31 AIMs for the Sequenome iPLEX system were selected and found to be highly informative for inferring ancestry among the seven continental regions Africa, the Middle East, Europe, Central/South Asia, East Asia, the Americas and Oceania. The panel was found to be least informative for Eurasian populations, and additional AIMs for a higher resolution are suggested. A large reference set including over 4,000 subjects collected from 120 global populations was assembled to facilitate accurate ancestry determination. We show practical applications of this AIM panel, discuss its limitations for admixed individuals and suggest ways to incorporate ancestry information into genetic association studies. We demonstrated the utility of a small AISNP panel specifically developed to discern global ancestry. We believe that it will find wide application because of its feasibility and potential for a wide range of applications.