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首页> 外文期刊>Investigative Genetics >Contrasting signals of positive selection in genes involved in human skin-color variation from tests based on SNP scans and resequencing
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Contrasting signals of positive selection in genes involved in human skin-color variation from tests based on SNP scans and resequencing

机译：来自基于SNP扫描和重测序的测试中与人类肤色变化有关的基因中阳性选择的对比信号

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Background Numerous genome-wide scans conducted by genotyping previously ascertained single-nucleotide polymorphisms (SNPs) have provided candidate signatures for positive selection in various regions of the human genome, including in genes involved in pigmentation traits. However, it is unclear how well the signatures discovered by such haplotype-based test statistics can be reproduced in tests based on full resequencing data. Four genes (oculocutaneous albinism II (OCA2), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT), and KIT ligand (KITLG)) implicated in human skin-color variation, have shown evidence for positive selection in Europeans and East Asians in previous SNP-scan data. In the current study, we resequenced 4.7 to 6.7 kb of DNA from each of these genes in Africans, Europeans, East Asians, and South Asians. Results Applying all commonly used neutrality-test statistics for allele frequency distribution to the newly generated sequence data provided conflicting results regarding evidence for positive selection. Previous haplotype-based findings could not be clearly confirmed. Although some tests were marginally significant for some populations and genes, none of them were significant after multiple-testing correction. Combined P values for each gene-population pair did not improve these results. Application of Approximate Bayesian Computation Markov chain Monte Carlo based to these sequence data using a simple forward simulator revealed broad posterior distributions of the selective parameters for all four genes, providing no support for positive selection. However, when we applied this approach to published sequence data on SLC45A2, another human pigmentation candidate gene, we could readily confirm evidence for positive selection, as previously detected with sequence-based and some haplotype-based tests. Conclusions Overall, our data indicate that even genes that are strong biological candidates for positive selection and show reproducible signatures of positive selection in SNP scans do not always show the same replicability of selection signals in other tests, which should be considered in future studies on detecting positive selection in genetic data.
机译：背景技术通过对先前确定的单核苷酸多态性（SNP）进行基因分型来进行的全基因组范围扫描，为在人类基因组各个区域（包括与色素沉着性状相关的基因）中进行阳性选择提供了候选特征。但是，尚不清楚在基于完全重测序数据的测试中，这种基于单倍型的测试统计数据发现的签名能否被很好地再现。涉及人类肤色变化的四个基因（眼白化病II（OCA2），酪氨酸酶相关蛋白1（TYRP1），多巴色素互变异构酶（DCT）和KIT配体（KITLG））已显示出在欧洲人和东方人中积极选择的证据亚洲人以前的SNP扫描数据。在当前的研究中，我们对非洲人，欧洲人，东亚人和南亚人中每个基因的4.7至6.7 kb DNA进行了重测序。结果将所有常用的用于等位基因频率分布的中性测试统计数据应用于新生成的序列数据，可提供与阳性选择证据有关的矛盾结果。以前基于单体型的发现无法明确确认。尽管某些测试对某些种群和基因仅具有微不足道的意义，但经过多次测试校正后，它们均无统计学意义。每个基因种群对的组合P值并不能改善这些结果。使用简单的正向模拟器基于这些序列数据的近似贝叶斯计算马尔可夫链蒙特卡罗方法，揭示了所有四个基因选择参数的广泛后验分布，不支持正选择。但是，当我们将这种方法应用于另一个人类色素沉着候选基因SLC45A2的公开序列数据时，我们可以很容易地确认阳性选择的证据，如先前基于序列和基于单倍型的检测所发现的。结论总体而言，我们的数据表明，即使是强阳性候选生物的基因，并且在SNP扫描中显示出阳性选择的可重现签名，也不一定总是在其他测试中显示出相同的选择信号可复制性，因此在以后的检测研究中应考虑使用遗传数据中的阳性选择。

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