A high resolution genome-wide scan for significant selective sweeps: an application to pooled sequence data in laying chickens.

A high resolution genome-wide scan for significant selective sweeps: an application to pooled sequence data in laying chickens.
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DOI:
10.1371/journal.pone.0049525
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Simianer H
Simianer H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Qanbari S;Strom TM;Haberer G;Weigend S;Gheyas AA;Turner F;Burt DW;Preisinger R;Gianola D;Simianer H

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在大多数旨在定位过去选择的足迹的研究中,给定检验统计量的经验分布的尾部的异常值被假设为反映特定于座位的选择力量。重要性的界限是主观确定的,而不是与一系列明确的假设有关。在这里,我们通过使用在真实数据中观察到的SNP结构的置换方法来定义汇总统计量的经验p值。为了说明我们的方法,我们将我们的方法应用于290万个常染色体SNPs的小组,这些SNPs是通过对棕色蛋鸡品系中的15个个体进行重新测序而确定的。我们扫描了基因组,以寻找局部杂合性降低,这暗示了选择性扫描。我们还采用了一种改进的滑动窗口方法,该方法解决了序列中的间隙,并通过仅以一个SNP的步长移动重叠窗口来提高扫描分辨率,并建议将其称为“爬行窗口”策略。该方法证实了以前描述的候选基因区域的选择性扫描,即TSHR、PRL、PRLHR、INSR、LEPR、IGF1和NRAMP1作为阳性对照。基因组扫描显示了82个具有强烈选择证据的不同区域(全基因组p-Value<0.001),包括分别与蛋壳结构和免疫系统相关的已知基因,如CALB1和GAL簇。在基因含量较低的区域发现了相当大比例的信号,包括1号染色体上最极端的信号。在一个高度选择的蛋鸡品系中观察到多个信号,这与产蛋是一个由许多基因控制的复杂性状的假设一致。
In most studies aimed at localizing footprints of past selection, outliers at tails of the empirical distribution of a given test statistic are assumed to reflect locus-specific selective forces. Significance cutoffs are subjectively determined, rather than being related to a clear set of hypotheses. Here, we define an empirical p-value for the summary statistic by means of a permutation method that uses the observed SNP structure in the real data. To illustrate the methodology, we applied our approach to a panel of 2.9 million autosomal SNPs identified from re-sequencing a pool of 15 individuals from a brown egg layer line. We scanned the genome for local reductions in heterozygosity, suggestive of selective sweeps. We also employed a modified sliding window approach that accounts for gaps in the sequence and increases scanning resolution by moving the overlapping windows by steps of one SNP only, and suggest to call this a “creeping window” strategy. The approach confirmed selective sweeps in the region of previously described candidate genes, i.e. TSHR, PRL, PRLHR, INSR, LEPR, IGF1, and NRAMP1 when used as positive controls. The genome scan revealed 82 distinct regions with strong evidence of selection (genome-wide p-value<0.001), including genes known to be associated with eggshell structure and immune system such as CALB1 and GAL cluster, respectively. A substantial proportion of signals was found in poor gene content regions including the most extreme signal on chromosome 1. The observation of multiple signals in a highly selected layer line of chicken is consistent with the hypothesis that egg production is a complex trait controlled by many genes.
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