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在不具备个体基因型的情况下进行全基因组选择扫描时考虑连锁不平衡:局部评分法。

Accounting for linkage disequilibrium in genome scans for selection without individual genotypes: The local score approach.

作者信息

Fariello María Inés, Boitard Simon, Mercier Sabine, Robelin David, Faraut Thomas, Arnould Cécile, Recoquillay Julien, Bouchez Olivier, Salin Gérald, Dehais Patrice, Gourichon David, Leroux Sophie, Pitel Frédérique, Leterrier Christine, SanCristobal Magali

机构信息

INRA, INPT, INP-ENVT, UMR1388, GenPhySE, Université de Toulouse, Castanet-Tolosan, France.

Facultad de Ingeniería, Universidad de la República, Montevideo, Uruguay.

出版信息

Mol Ecol. 2017 Jul;26(14):3700-3714. doi: 10.1111/mec.14141. Epub 2017 May 21.

Abstract

Detecting genomic footprints of selection is an important step in the understanding of evolution. Accounting for linkage disequilibrium in genome scans increases detection power, but haplotype-based methods require individual genotypes and are not applicable on pool-sequenced samples. We propose to take advantage of the local score approach to account for linkage disequilibrium in genome scans for selection, cumulating (possibly small) signals from single markers over a genomic segment, to clearly pinpoint a selection signal. Using computer simulations, we demonstrate that this approach detects selection with higher power than several state-of-the-art single-marker, windowing or haplotype-based approaches. We illustrate this on two benchmark data sets including individual genotypes, for which we obtain similar results with the local score and one haplotype-based approach. Finally, we apply the local score approach to Pool-Seq data obtained from a divergent selection experiment on behaviour in quail and obtain precise and biologically coherent selection signals: while competing methods fail to highlight any clear selection signature, our method detects several regions involving genes known to act on social responsiveness or autistic traits. Although we focus here on the detection of positive selection from multiple population data, the local score approach is general and can be applied to other genome scans for selection or other genomewide analyses such as GWAS.

摘要

检测选择的基因组印记是理解进化过程中的重要一步。在基因组扫描中考虑连锁不平衡可提高检测能力,但基于单倍型的方法需要个体基因型,不适用于混合测序样本。我们建议利用局部得分方法在基因组扫描中考虑连锁不平衡以检测选择,将单个标记(可能较小)的信号累积在一个基因组片段上,从而清晰地定位选择信号。通过计算机模拟,我们证明该方法比几种先进的单标记、窗口化或基于单倍型的方法具有更高的检测选择的能力。我们在两个包含个体基因型的基准数据集上进行了说明,在这些数据集上我们使用局部得分方法和一种基于单倍型的方法获得了相似的结果。最后,我们将局部得分方法应用于鹌鹑行为差异选择实验获得的混合测序数据,并获得了精确且生物学上连贯的选择信号:而其他竞争方法未能突出任何明显的选择特征时,我们的方法检测到了几个涉及已知影响社会反应性或自闭症特征基因的区域。尽管我们在此重点关注从多个群体数据中检测正选择,但局部得分方法具有通用性,可应用于其他选择的基因组扫描或其他全基因组分析,如全基因组关联研究(GWAS)。

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