Ascertainment Biases in SNP Chips Affect Measures of Population Divergence
Ascertainment Biases in SNP Chips Affect Measures of Population Divergence
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DOI：
10.1093/molbev/msq148
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发表时间：
2010-11-01
影响因子：
10.7
通讯作者：
Nielsen, Rasmus
中科院分区：
文献类型：
--
作者：
Albrechtsen, Anders;Nielsen, Finn Cilius;Nielsen, Rasmus
基于芯片的高通量基因分型促进了全基因组遗传多样性的研究。许多研究已经利用这些大数据集，使用遗传分化的措施，如F（ST）或主成分分析来推断人口的人口统计学历史。然而，单核苷酸多态性（SNP）芯片数据遭受由SNP发现过程引起的确定偏差，其中来自选定群体的少量个体被用作发现面板。在这项研究中，我们调查的影响，推断有关群体之间的遗传分化的一个常见的全基因组基因分型平台的确定偏差。我们生成SNP基因分型数据的个人，以前已经受到部分全基因组桑格测序和比较的推论的基础上，直接测序的基因分型数据的推论。此外，我们还分析了公开的全基因组数据。我们证明，确认偏见将扭曲人类多样性的措施，并可能改变从这些措施中得出的结论，在某些时候意想不到的方式。我们还表明，基因分型调用算法的细节可以有一个令人惊讶的大影响人口遗传推断。我们不仅提出了广泛使用的Affyssin SNP芯片的光谱校正，但也表明，这种校正是很难概括的研究。
Chip-based high-throughput genotyping has facilitated genome-wide studies of genetic diversity. Many studies have utilized these large data sets to make inferences about the demographic history of human populations using measures of genetic differentiation such as F(ST) or principal component analyses. However, the single nucleotide polymorphism (SNP) chip data suffer from ascertainment biases caused by the SNP discovery process in which a small number of individuals from selected populations are used as discovery panels. In this study, we investigate the effect of the ascertainment bias on inferences regarding genetic differentiation among populations in one of the common genome-wide genotyping platforms. We generate SNP genotyping data for individuals that previously have been subject to partial genome-wide Sanger sequencing and compare inferences based on genotyping data to inferences based on direct sequencing. In addition, we also analyze publicly available genome-wide data. We demonstrate that the ascertainment biases will distort measures of human diversity and possibly change conclusions drawn from these measures in some times unexpected ways. We also show that details of the genotyping calling algorithms can have a surprisingly large effect on population genetic inferences. We not only present a correction of the spectrum for the widely used Affymetrix SNP chips but also show that such corrections are difficult to generalize among studies.