Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies.
Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies.
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DOI：
10.1371/journal.pgen.1002641
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Tishkoff SA
中科院分区：
文献类型：
--
作者：
Jarvis JP;Scheinfeldt LB;Soi S;Lambert C;Omberg L;Ferwerda B;Froment A;Bodo JM;Beggs W;Hoffman G;Mezey J;Tishkoff SA
非洲俾格米人群体表现出独特的表型变异模式，包括身材矮小，这被认为反映了过去对热带环境的适应。在这里，我们分析了Illumina 1 M SNP阵列数据在三个西部俾格米人从喀麦隆和三个相邻的班图语的农业人口与他们混合。我们推断全基因组的祖先，扫描积极选择的信号，并执行有针对性的遗传关联与测量的高度变化。我们确定了整个基因组中可能在适应性进化中发挥作用的多个区域，其中许多区域包含在生长激素，胰岛素和胰岛素样生长因子信号通路中发挥作用的基因座，以及参与生殖和代谢的免疫和神经内分泌信号。最引人注目的结果发现在3号染色体上，其中包含一组约45和60 Mb之间的选择和关联信号。该区域还包括已知与欧洲人身高变化相关的位置候选基因DOCK 3，以及已知抑制生长激素刺激的STAT 5信号传导的细胞因子信号传导负调控因子CISH。最后，对与身高相关的最强信号附近的基因的通路分析表明，参与胰岛素和胰岛素样生长因子信号传导的基因座富集。非洲被认为是过去20万年来现代人类的起源地，也是过去10万年来我们分散到地球仪各地的源头。非洲也是一个极端的环境，文化，语言和表型多样性的地区，生活在那里的人口显示出世界上最高水平的遗传多样性。然而，人们对在非洲观察到的表型变异的遗传基础以及当地适应和人口统计学如何在最近的过去影响这些模式知之甚少。在这里，我们分析了一组混合班图语的农业和西部俾格米狩猎采集人口，显示出极端的身高差异;俾格米人平均比他们的班图邻居矮17厘米，是全球最短的人口之一。我们的多方面的方法确定了几个基因组区域，这些区域可能是自然选择的目标，因此可能包含西非俾格米人独特的解剖学和生理学基础的变体。特别是第三号染色体的一个区域，隐藏着自然选择、种群分化和与身高相关的强烈信号。该区域还包含与欧洲人身高的显着关联，以及已知调节生长激素信号的候选基因。
African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling. Africa is thought to be the location of origin of modern humans within the past 200,000 years and the source of our dispersion across the globe within the past 100,000 years. Africa is also a region of extreme environmental, cultural, linguistic, and phenotypic diversity, and human populations living there show the highest levels of genetic diversity in the world. Yet little is known about the genetic basis of the observed phenotypic variation in Africa or how local adaptation and demography have influenced these patterns in the recent past. Here, we analyze a set of admixing Bantu-speaking agricultural and Western Pygmy hunter-gatherer populations that show extreme differences in stature; Pygmies are ∼17 cm shorter on average than their Bantu neighbors and among the shortest populations globally. Our multifaceted approach identified several genomic regions that may have been targets of natural selection and so may harbor variants underlying the unique anatomy and physiology of Western African Pygmies. One region of chromosome three, in particular, harbors strong signals of natural selection, population differentiation, and association with height. This region also contains a significant association with height in Europeans as well as a candidate gene known to regulate growth hormone signaling.
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影响因子：
3.7
作者：
López Herráez D;Bauchet M;Tang K;Theunert C;Pugach I;Li J;Nandineni MR;Gross A;Scholz M;Stoneking M
通讯作者：
Stoneking M
影响因子：
9.8
作者：
Boyko AR;Quignon P;Li L;Schoenebeck JJ;Degenhardt JD;Lohmueller KE;Zhao K;Brisbin A;Parker HG;vonHoldt BM;Cargill M;Auton A;Reynolds A;Elkahloun AG;Castelhano M;Mosher DS;Sutter NB;Johnson GS;Novembre J;Hubisz MJ;Siepel A;Wayne RK;Bustamante CD;Ostrander EA
通讯作者：
Ostrander EA
影响因子：
1.3
作者：
Ballard, C
通讯作者：
Ballard, C
影响因子：
64.8
作者：
Joron, Mathieu;Frezal, Lise;Jones, Robert T.;Chamberlain, Nicola L.;Lee, Siu F.;Haag, Christoph R.;Whibley, Annabel;Becuwe, Michel;Baxter, Simon W.;Ferguson, Laura;Wilkinson, Paul A.;Salazar, Camilo;Davidson, Claire;Clark, Richard;Quail, Michael A.;Beasley, Helen;Glithero, Rebecca;Lloyd, Christine;Sims, Sarah;Jones, Matthew C.;Rogers, Jane;Jiggins, Chris D.;Ffrench-Constant, Richard H.
通讯作者：
Ffrench-Constant, Richard H.
影响因子：
4.4
作者：
Huff CD;Harpending HC;Rogers AR
通讯作者：
Rogers AR