An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

被引：107

作者：

Martin, Alicia R. ^{[1
,2
,3
,4
,5
]}

Lin, Meng ^{[6
]}

Granka, Julie M. ^{[7
,14
]}

Myrick, Justin W. ^{[6
]}

Liu, Xiaomin ^{[8
]}

Sockell, Alexandra ^{[1
]}

Atkinson, Elizabeth G. ^{[6
]}

Werely, Cedric J. ^{[9
]}

Moller, Marlo ^{[9
]}

Sandhu, Manjinder S. ^{[10
]}

Kingsley, David M. ^{[11
]}

Hoal, Eileen G. ^{[9
]}

Liu, Xiao ^{[8
]}

Daly, Mark J. ^{[2
,3
,4
,5
]}

Feldman, Marcus W. ^{[7
]}

Gignoux, Christopher R. ^{[1
,12
,13
]}

Bustamante, Carlos D. ^{[1
]}

Henn, Brenna M. ^{[6
]}

机构：

[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[2] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[3] Harvard Med Sch, Boston, MA 02114 USA

[4] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02141 USA

[5] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02141 USA

[6] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA

[7] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA

[8] BGI Shenzhen, Shenzhen, Guangdong, Peoples R China

[9] Stellenbosch Univ, SA MRC Ctr TB Res, DST NRF Ctr Excellence Biomed TB Res, Div Mol Biol & Human Genet,Fac Med & Hlth Sci, Cape Town, South Africa

[10] Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England

[11] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA

[12] Univ Colorado, Colorado Ctr Personalized Med, Anschutz Med Campus, Aurora, CO 80045 USA

[13] Univ Colorado, Dept Biostat & Informat, Anschutz Med Campus, Aurora, CO 80045 USA

[14] AncestryDNA, San Francisco, CA 94107 USA

来源：

CELL | 2017年 / 171卷 / 06期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-DETERMINANTS; TRANSCRIPTION FACTOR; REVEALS ADAPTATION; EYE-COLOR; HAIR; EXPRESSION; SOUTHERN; COMMON; HERITABILITY;

D O I：

10.1016/j.cell.2017.11.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Approximately 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed, with genetic architecture varying by latitude. We investigate polygenicity in the KhoeSan populations indigenous to southern Africa who have considerably lighter skin than equatorial Africans. We demonstrate that skin pigmentation is highly heritable, butknownpigmentation loci explainonly asmall fraction of the variance. Rather, baseline skin pigmentation is a complex, polygenic trait in the KhoeSan. Despite this, we identify canonical and non-canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR, and SNX13, using a genome-wide association approach complemented by targeted resequencing. By considering diverse, under-studied African populations, we show how the architecture of skin pigmentation can vary across humans subject to different local evolutionary pressures.

引用

页码：1340 / +

页数：28

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