Martin Alicia R, Lin Meng, Granka Julie M, Myrick Justin W, Liu Xiaomin, Sockell Alexandra, Atkinson Elizabeth G, Werely Cedric J, Möller Marlo, Sandhu Manjinder S, Kingsley David M, Hoal Eileen G, Liu Xiao, Daly Mark J, Feldman Marcus W, Gignoux Christopher R, Bustamante Carlos D, Henn Brenna M
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.
Department of Ecology and Evolution, SUNY Stony Brook, NY 11794, USA.
Cell. 2017 Nov 30;171(6):1340-1353.e14. doi: 10.1016/j.cell.2017.11.015.
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.
大约有15个基因与人类皮肤色素沉着变异直接相关，这使得皮肤色素沉着被视为一种相对简单的性状。然而，通过对全球定量皮肤色素沉着表型进行全面调查，我们发现色素沉着比之前认为的更为复杂，其遗传结构因纬度而异。我们对非洲南部的科伊桑人群进行了多基因性研究，该人群的皮肤比赤道非洲人浅得多。我们发现皮肤色素沉着具有高度遗传性，但已知的色素沉着基因座仅解释了一小部分变异。相反，在科伊桑人群中，基线皮肤色素沉着是一种复杂的多基因性状。尽管如此，我们通过全基因组关联研究方法并辅以靶向重测序，确定了典型和非典型的皮肤色素沉着基因座，包括靠近SLC24A5、TYRP1、SMARCA2/VLDLR和SNX13的基因座。通过研究多样化且研究较少的非洲人群，我们展示了在不同局部进化压力下，人类皮肤色素沉着的结构是如何变化的。
