Signatures of Long-Term Balancing Selection in Human Genomes.
Signatures of Long-Term Balancing Selection in Human Genomes.
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DOI：
10.1093/gbe/evy054
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发表时间：
2018-03-01
影响因子：
3.3
通讯作者：
Andrés AM
中科院分区：
文献类型：
--
作者：
Bitarello BD;de Filippo C;Teixeira JC;Schmidt JM;Kleinert P;Meyer D;Andrés AM
平衡选择通过各种机制维持种群的有利多样性。虽然从理论的角度进行了广泛的探索，但对它的普遍性和目标的实证理解落后于我们对积极选择的认识。在这里，我们描述了非中心偏差（NCD），一个简单而强大的统计来检测长期平衡选择（LTBS），量化的频率是多么接近预期下LTBS，并提供了一个中立性测试的基础。NCD可以应用于单个基因座或基因组数据，并且可以仅考虑多态性（NCD 1）或还考虑相对于外群（NCD 2）物种的固定差异来实施。消除固定差异提高了功效，并且NCD2在平衡等位基因的不同频率下具有比其他可用方法更高的功效来检测人类中的LTBS。应用于非洲和欧洲人群的全基因组数据，在两种情况下使用黑猩猩作为外群，NCD2显示，尽管不普遍，但LTBS影响了基因组的相当大的一部分：约0.6%的分析基因组窗口和0.8%的分析位置。显著性窗口（P < 0.0001）包含基因组中1.6%的SNP，这些SNP优先落在外显子内并改变蛋白质序列，但不富集在p53调控位点。这些窗口与蛋白质编码基因的0.8%重叠，即使在控制基因长度后，这些基因的转录本数量也比预期的要多。我们的目录包括LTBS的已知目标，但其中大多数（90%）是新的。正如预期的那样，免疫相关基因是具有最强特征的基因之一，尽管大多数候选基因涉及其他生物学功能，这表明LTBS可能影响多种人类表型。
Balancing selection maintains advantageous diversity in populations through various mechanisms. Although extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here, we describe the Non-central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to a single locus or genomic data, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences with respect to an outgroup (NCD2) species. Incorporating fixed differences improves power, and NCD2 has higher power to detect LTBS in humans under different frequencies of the balanced allele(s) than other available methods. Applied to genome-wide data from African and European human populations, in both cases using chimpanzee as an outgroup, NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: ∼0.6% of analyzed genomic windows and 0.8% of analyzed positions. Significant windows (P < 0.0001) contain 1.6% of SNPs in the genome, which disproportionally fall within exons and change protein sequence, but are not enriched in putatively regulatory sites. These windows overlap ∼8% of the protein-coding genes, and these have larger number of transcripts than expected by chance even after controlling for gene length. Our catalog includes known targets of LTBS but a majority of them (90%) are novel. As expected, immune-related genes are among those with the strongest signatures, although most candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Danjou F;Zoledziewska M;Sidore C;Steri M;Busonero F;Maschio A;Mulas A;Perseu L;Barella S;Porcu E;Pistis G;Pitzalis M;Pala M;Menzel S;Metrustry S;Spector TD;Leoni L;Angius A;Uda M;Moi P;Thein SL;Galanello R;Abecasis GR;Schlessinger D;Sanna S;Cucca F
通讯作者：
Cucca F
影响因子：
--
作者：
Andreychenko, Aleksandr;Crouzen, Pepijn;Wolf, Verena
通讯作者：
Wolf, Verena
影响因子：
30.8
作者：
Alkan, Can;Kidd, Jeffrey M.;Marques-Bonet, Tomas;Aksay, Gozde;Antonacci, Francesca;Hormozdiari, Fereydoun;Kitzman, Jacob O.;Baker, Carl;Malig, Maika;Mutlu, Onur;Sahinalp, S. Cenk;Gibbs, Richard A.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
2.1
作者：
Aouizerat BE;Vittinghoff E;Musone SL;Pawlikowska L;Kwok PY;Olgin JE;Tseng ZH
通讯作者：
Tseng ZH