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Cell. 2017 Nov 30;171(6):1340-1353.e14. doi: 10.1016/j.cell.2017.11.015.

An Unexpectedly Complex Architecture for Skin Pigmentation in Africans.

Author information

1
Department of Genetics, Stanford University, Stanford, CA 94305, USA; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02141, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02141, USA. Electronic address: armartin@broadinstitute.org.
2
Department of Ecology and Evolution, SUNY Stony Brook, NY 11794, USA.
3
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
4
BGI-Shenzhen, Shenzhen, Guangdong, China.
5
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
6
SA MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa.
7
Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.
8
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
9
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02141, USA; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02141, USA.
10
Department of Ecology and Evolution, SUNY Stony Brook, NY 11794, USA. Electronic address: brenna.henn@stonybrook.edu.

Abstract

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, but known pigmentation loci explain only a small 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.

KEYWORDS:

Africa; heritability; human evolution; pigmentation; population genetics

Comment in

PMID:
29195075
PMCID:
PMC5884124
DOI:
10.1016/j.cell.2017.11.015
[Indexed for MEDLINE]
Free PMC Article

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