ADMIXTURE AS A TOOL FOR FINDING LINKED GENES AND DETECTING THAT DIFFERENCE FROM ALLELIC ASSOCIATION BETWEEN LOCI
ADMIXTURE AS A TOOL FOR FINDING LINKED GENES AND DETECTING THAT DIFFERENCE FROM ALLELIC ASSOCIATION BETWEEN LOCI
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DOI：
10.1073/pnas.85.23.9119
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发表时间：
1988-12-01
影响因子：
11.1
通讯作者：
WEISS, KM
中科院分区：
文献类型：
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作者：
CHAKRABORTY, R;WEISS, KM
遗传不同群体之间的混合可能会在基因位点之间产生配子关联，作为亲代群体之间的遗传差异和混合率的函数。这种关联随着混合后的时间和基因座之间的重组率而衰减。自探索和殖民时代以来的几个世纪以来，基因上长期分离的人类群体之间的混合一直很频繁，导致今天出现了大量的杂交后代群体，就像在美洲一样。这代表了遗传流行病学和人类学的自然实验，其中使用多态性标记位点（例如限制性片段长度多态性）和不平衡来推断感兴趣性状的遗传基础。在本文中，我们表明，在广泛适用的情况下，今天仍然存在严重的不平衡，无需性状和标记基因座之间异常紧密的联系即可检测到这种不平衡。非常不同的亲本等位基因频率会产生很大的不平衡，但由于混合群体中单倍型频率分布的倾斜，检测这种不平衡水平所需的样本量可能很大。然而，这种情况提供了区分仅由于种群混合而导致的不平衡与由于基因座的物理连锁而导致的不平衡的能力，即帮助绘制性状的遗传基因座。相同亲本群体之间的混合水平梯度可用于通过将混合与不平衡水平相关联来测试遗传模型。
Admixture between genetically different populations may produce gametic association between gene loci as a function of the genetic difference between parental populations and the admixture rate. This association decays as a function of time since admixture and the recombination rate between the loci. Admixture between genetically long-separated human populations has been frequent in the centuries since the age of exploration and colonization, resulting in numerous hybrid descendant populations today, as in the Americas. This represents a natural experiment for genetic epidemiology and anthropology, in which to use polymorphic marker loci (e.g., restriction fragment length polymorphisms) and disequilibrium to infer a genetic basis for traits of interest. In this paper we show that substantial disequilibrium remains today under widely applicable situations, which can be detected without requiring inordinately close linkage between trait and marker loci. Very disparate parental allele frequencies produce large disequilibrium, but the sample size needed to detect such levels of disequilibrium can be large due to the skewed haplotype frequency distribution in the admixed population. Such situations, however, provide power to differentiate between disequilibrium due just to population mixing from that due to physical linkage of loci-i.e., to help map the genetic locus of the trait. A gradient of admixture levels between the same parental populations may be used to test genetic models by relating admixture to disequilibrium levels.