Loci associated with skin pigmentation identified in African populations

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

doi:10.1126/science.aan8433

Loci associated with skin pigmentation identified in African populations

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

Authors

Nicholas G Crawford¹, Derek E Kelly^{1

2}, Matthew E B Hansen¹, Marcia H Beltrame¹, Shaohua Fan¹, Shanna L Bowman^{3

4}, Ethan Jewett^{5

6}, Alessia Ranciaro¹, Simon Thompson¹, Yancy Lo¹, Susanne P Pfeifer⁷, Jeffrey D Jensen⁷, Michael C Campbell^{1

8}, William Beggs¹, Farhad Hormozdiari^{9

10}, Sununguko Wata Mpoloka¹¹, Gaonyadiwe George Mokone¹², Thomas Nyambo¹³, Dawit Wolde Meskel¹⁴, Gurja Belay¹⁴, Jake Haut¹; NISC Comparative Sequencing Program; Harriet Rothschild¹⁵, Leonard Zon^{15

16}, Yi Zhou^{15

17}, Michael A Kovacs¹⁸, Mai Xu¹⁸, Tongwu Zhang¹⁸, Kevin Bishop¹⁹, Jason Sinclair¹⁹, Cecilia Rivas²⁰, Eugene Elliot²⁰, Jiyeon Choi¹⁸, Shengchao A Li^{21

22}, Belynda Hicks^{21

22}, Shawn Burgess¹⁹, Christian Abnet²¹, Dawn E Watkins-Chow²⁰, Elena Oceana²³, Yun S Song^{5

6

24

25

26}, Eleazar Eskin²⁷, Kevin M Brown¹⁸, Michael S Marks^{3

4}, Stacie K Loftus²⁰, William J Pavan²⁰, Meredith Yeager^{21

22}, Stephen Chanock²¹, Sarah A Tishkoff^{28

25}

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Africa, Eastern
Animals
Antiporters / genetics
Black People / genetics*
DNA-Binding Proteins / genetics
Ethnicity / genetics
Evolution, Molecular*
Gene Flow*
Genetic Loci*
Genome, Human
Genome-Wide Association Study
Humans
Melanins / biosynthesis
Melanins / genetics*
Melanins / metabolism
Melanocytes / metabolism
Membrane Proteins / genetics
Mice
Polymorphism, Single Nucleotide
Radiation Exposure
Skin Pigmentation / genetics*
Suppression, Genetic
Ultraviolet Rays

Substances

Antiporters
DDB1 protein, human
DNA-Binding Proteins
MFSD12 protein, human
Melanins
Membrane Proteins
SLC24A5 protein, human
TMEM138 protein, human
eumelanin

Abstract

Publication types

MeSH terms

Substances

Grants and funding