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Science. 2017 Nov 17;358(6365). pii: eaan8433. doi: 10.1126/science.aan8433. Epub 2017 Oct 12.

Loci associated with skin pigmentation identified in African populations.

Author information

1
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Genomics and Computational Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.
4
Department of Pathology and Laboratory Medicine and Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94704, USA.
6
Department of Statistics, University of California, Berkeley, Berkeley, CA 94704, USA.
7
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
8
Department of Biology, Howard University, Washington, DC 20059, USA.
9
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
10
Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
11
Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
12
Department of Biomedical Sciences, University of Botswana School of Medicine, Gaborone, Botswana.
13
Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
14
Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia.
15
Stem Cell Program, Division of Hematology and Oncology, Pediatric Hematology Program, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
16
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
17
Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
18
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
19
Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
20
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
21
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
22
Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21701, USA.
23
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA.
24
Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
25
Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
26
Department of Mathematics, University of Pennsylvania, Philadelphia, PA 19104, USA.
27
Department of Computer Science and Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
28
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. tishkoff@pennmedicine.upenn.edu.

Abstract

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 zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians.

PMID:
29025994
PMCID:
PMC5759959
DOI:
10.1126/science.aan8433
[Indexed for MEDLINE]
Free PMC Article

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