Journal Article

Loci associated with skin pigmentation identified in African populations

Elliot, Eugene, Rothschild, Harriet, Marks, Michael S., Xu, Mai, Song, Yun S., Nyambo, Thomas, Abnet, Christian, Beggs, William, Oceana, Elena, Eskin, Eleazar, Belay, Gurja, Choi, Jiyeon, Burgess, Shawn, Kelly, Derek E., Jewett, Ethan, Haut, Jake, Hicks, Belynda, Pfeifer, Susanne P., Sinclair, Jason, Bishop, Kevin, Kovacs, Michael A., Zon, Leonard, Mokone, Gaonyadiwe George, Hormozdiari, Farhad, Campbell, Michael C., Ranciaro, Alessia, Brown, Kevin M., Crawford, Nicholas G., Pavan, William J., Beltrame, Marcia H., Jensen, Jeffrey D., Mpoloka, Sununguko Wata, Bowman, Shanna L., Zhang, Tongwu, Watkins-Chow, Dawn E., Yeager, Meredith, Rivas, Cecilia, Hansen, Matthew E. B., Fan, Shaohua, Li, Shengchao A., Lo, Yancy, Meskel, Dawit Wolde, NISC Comparative Sequencing Program, Chanock, Stephen, Zhou, Yi, Thompson, Simon, Tishkoff, Sarah A., Loftus, Stacie K.

2017

Overview

Skin color varies among human populations and is thought to be under selection, with light skin maximizing vitamin D production at higher latitudes and dark skin providing UV protection in equatorial zones. To identify the genes that give rise to the palette of human skin tones, Crawford et al. applied genome-wide analyses across diverse African populations (see the Perspective by Tang and Barsh). Genetic variants were identified with likely function in skin phenotypes. Comparison to model organisms verified a conserved function of MFSD12 in pigmentation. A global genetic panel was used to trace how alleles associated with skin color likely moved across the globe as humans migrated, both within and out of Africa. Science , this issue p. eaan8433 ; see also p. 867 Genome-wide analysis of 2000 Africans identifies and functionally characterizes pigmentation loci. Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5 , MFSD12 , DDB1 , TMEM138 , OCA2 , and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in South Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adaptiveness / Africa, Eastern / Alleles / Alternative splicing / Animals / Antiporters - genetics / Biological evolution / Biology / Black People - genetics / Correlation / Danio rerio / Dark adaptation / Deoxyribonucleic acid / DNA / DNA damage / DNA repair / DNA-Binding Proteins - genetics / Equatorial regions / Ethnicity - genetics / Evolution, Molecular / Evolutionary genetics / Gene expression / Gene Flow / Gene mapping / Genes / Genetic diversity / Genetic Loci / Genetic variance / Genetics / Genome, Human / Genome-wide association studies / Genome-Wide Association Study / Genomes / Human populations / Humans / Light / Lysosomal protein / Melanin / Melanins - biosynthesis / Melanins - genetics / Melanins - metabolism / Melanocytes / Melanocytes - metabolism / Membrane Proteins - genetics / Mice / Migration / Mutation / Phenotypic variations / Pigmentation / Polymorphism, Single Nucleotide / Population genetics / Population studies / Populations / Positive selection / Proteins / Radiation Exposure / Regulatory sequences / RESEARCH ARTICLE SUMMARY / Skin / Skin pigmentation / Skin Pigmentation - genetics / Splicing / Suppression, Genetic / Transcription / Ultraviolet Rays / Vitamin D / Zebrafish