Human population genetic structure and inference of group membership
Human population genetic structure and inference of group membership
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DOI：
10.1086/368061
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发表时间：
2003-03-01
影响因子：
9.8
通讯作者：
Jorde, LB
中科院分区：
文献类型：
--
作者：
Bamshad, MJ;Wooding, S;Jorde, LB
生物医学研究的一个主要目标是发展提供高度个性化医疗保健的能力。要做到这一点，有必要了解个体间遗传变异在身体特征、疾病易感性和对治疗反应的基因座上的分布。这些位点的变异通常表现出地理结构，并可能导致组间的表型差异。因此，在某些情况下，单独考虑这些群体可能很重要。这些群体的成员身份通常是通过使用原籍地或族裔归属等替代来推断的。然而，这些推论经常被使用替代物（如肤色）来削弱，因为这些替代物的分布与中性遗传变异的分布几乎没有相似之处。因此，它已成为越来越有争议的代理是否是足够的和准确的代表性群体推断从中性遗传变异。这就提出了三个问题：需要多少数据才能在有意义的分辨率水平上识别人口结构，人口结构可以被分辨率到什么水平，以及某些代理是否准确地表示人口结构？我们检测了565个个体的100个Alu插入多态性，其中200个个体还检测了60个微卫星。去除识别信息后，平均准确率至少为90%的对原产大陆（非洲、亚洲或欧洲）的正确分配需要至少60个Alu标记或微卫星，当使用大于或等于100个位点时，平均准确率达到99%-100%。不太准确的分配（87%），以适当的遗传簇是可能的历史混合样品从印度南部。这些结果设定了一个最小的标记，必须进行测试，以作出强有力的推论，在理想的实验条件下检测旧世界人口的人口结构。我们注意到，虽然有些代理粗略地对应，如果有的话，人口结构，其他人的启发式价值要高得多。这表明，需要一个更灵活的框架来推断人口结构和代理的效用。
A major goal of biomedical research is to develop the capability to provide highly personalized health care. To do so, it is necessary to understand the distribution of interindividual genetic variation at loci underlying physical characteristics, disease susceptibility, and response to treatment. Variation at these loci commonly exhibits geographic structuring and may contribute to phenotypic differences between groups. Thus, in some situations, it may be important to consider these groups separately. Membership in these groups is commonly inferred by use of a proxy such as place-of-origin or ethnic affiliation. These inferences are frequently weakened, however, by use of surrogates, such as skin color, for these proxies, the distribution of which bears little resemblance to the distribution of neutral genetic variation. Consequently, it has become increasingly controversial whether proxies are sufficient and accurate representations of groups inferred from neutral genetic variation. This raises three questions: how many data are required to identify population structure at a meaningful level of resolution, to what level can population structure be resolved, and do some proxies represent population structure accurately? We assayed 100 Alu insertion polymorphisms in a heterogeneous collection of similar to565 individuals, similar to200 of whom were also typed for 60 microsatellites. Stripped of identifying information, correct assignment to the continent of origin (Africa, Asia, or Europe) with a mean accuracy of at least 90% required a minimum of 60 Alu markers or microsatellites and reached 99%-100% when greater than or equal to100 loci were used. Less accurate assignment (87%) to the appropriate genetic cluster was possible for a historically admixed sample from southern India. These results set a minimum for the number of markers that must be tested to make strong inferences about detecting population structure among Old World populations under ideal experimental conditions. We note that, whereas some proxies correspond crudely, if at all, to population structure, the heuristic value of others is much higher. This suggests that a more flexible framework is needed for making inferences about population structure and the utility of proxies.