Mixed Race Studies

Skin pigmentation is far more genetically complex than previously thought

Broad Institute
Massachusetts Institute of Technology, Cambridge, Massachusetts
2017-11-30

David Cameron, Director of Communications/Media Relations

Credit : Brenna Henn South African individuals in a household that exemplify the substantial skin pigmentation variability in the Khomani and Nama populations. Picture taken with consent for publication.

By studying an African population underrepresented in most datasets, researchers find genetic complexity of pigmentation varies by latitude

Many studies have suggested that the genetics of skin pigmentation are simple. A small number of known genes, it is thought, account for nearly 50 percent of pigment variation. However, these studies rely on datasets that heavily favor northern Eurasian populations—those that reside mostly in higher latitude regions.

Reporting in the November 30 issue of Cell, researchers from the Broad Institute of MIT and Harvard, Stanford University, and Stony Brook University report that while skin pigmentation is nearly 100 percent heritable, it is hardly a straightforward, Mendelian trait. By working closely with the KhoeSan, a group of populations indigenous to southern Africa, the researchers have found that the genetics of skin pigmentation become progressively complex as populations reside closer to the equator, with an increasing number of genes—known and unknown—involved, each making a smaller overall contribution.

“Africa has the greatest amount of phenotypic variability in skin color, and yet it’s been underrepresented in large scale endeavors,” said Alicia Martin, a postdoctoral scientist in the lab of Broad Institute member Mark Daly. “There are some genes that are known to contribute to skin pigmentation, but by and large there are many more new genes that have not been discovered.”

“We need to spend more time focusing on these understudied populations in order to gain deeper genetic insights,” said Brenna Henn, assistant professor in the Department of Ecology and Evolution at Stony Brook University who, along with Martin, is a co-corresponding author…

Read the entire article here.

An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

Cell
Volume 171, Issue 6, 2017-11-30
pages 1340–1353.e14
DOI: 10.1016/j.cell.2017.11.015

Alicia R. Martin, Meng Lin, Julie M. Granka, Justin W. Myrick, Xiaomin Liu, Alexandra Sockell, Elizabeth G. Atkinson, Cedric J. Werely, Marlo Möller, Manjinder S. Sandhu, David M. Kingsley, Eileen G. Hoal, Xiao Liu, Mark J. Daly, Marcus W. Feldman, Christopher R. Gignoux, Carlos D. Bustamante, Brenna M. Henn

Highlights

• Skin pigmentation in Africans is far more polygenic than light skin in Eurasians
• Southern African KhoeSan populations have lighter skin compared to equatorial Africans
• Highly heritable KhoeSan skin color variation is poorly explained by known genes
• The study of African skin color identifies novel and canonical pigmentation genes

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.

Read or purchase the article here.