The Genome-wide Patterns of Variation Expose Significant Substructure in a Founder Population
The Genome-wide Patterns of Variation Expose Significant Substructure in a Founder Population
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DOI：
10.1016/j.ajhg.2008.11.005
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发表时间：
2008-12-12
影响因子：
9.8
通讯作者：
Peltonen, Leena
中科院分区：
文献类型：
--
作者：
Jakkula, Eveliina;Rehnstroem, Karola;Peltonen, Leena
尽管高密度 SNP 基因分型平台为详细的全基因组关联 (GWA) 研究带来了动力，但它的一个分支是对群体遗传学的新见解。在这里，我们通过仔细研究十个不同的芬兰早期和晚期定居亚群体，以最著名的创始人群体之一为例。通过确定遗传距离、纯合性和连锁不平衡模式，我们证明群体亚结构，甚至个体祖先，可以以非常高的分辨率检测到，并支持连续创始人效应导致的多个历史瓶颈的概念。鉴于遗传研究目前的目标是识别越来越小的遗传效应，即使在如此精细的水平上识别和控制群体亚结构也变得至关重要，以避免混淆和虚假关联。这项研究提供了一个例子，说明 GWA 数据集的力量可以证明人口历史造成的分层，即使是在芬兰人等看似同质的人口中也是如此。此外，这些结果提供了关于人口历史对人类基因组景观的影响的有趣教训，以及识别这些亚群中丰富的罕见变异的方法。
Although high-density SNP genotyping platforms generate a momentum for detailed genome-wide association (GWA) studies, an offshoot is a new insight into population genetics. Here, we present an example in one of the best-known founder populations by scrutinizing ten distinct Finnish early- and late-settlement subpopulations. By determining genetic distances, homozygosity, and patterns of linkage disequilibrium, we demonstrate that population substructure, and even individual ancestry, is detectable at a very high resolution and Supports the concept of multiple historical bottlenecks resulting from consecutive founder effects. Given that genetic studies are currently aiming at identifying smaller and smaller genetic effects, recognizing and controlling for population substructure even at this fine level becomes imperative to avoid confounding and spurious associations. This study provides an example of the power of GWA data sets to demonstrate stratification caused by population history even within a seemingly homogeneous population, like the Finns. Further, the results provide interesting lessons concerning the impact of population history on the genome landscape of humans, as well as approaches to identify rare variants enriched in these subpopulations.