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; 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 Tishkoff

doi:10.1126/science.aan8433

Research Article

Loci associated with skin pigmentation identified in African populations

Nicholas G. Crawford¹,
Derek E. Kelly¹,²,*,
Matthew E. B. Hansen¹,*,
Marcia H. Beltrame¹,*,
Shaohua Fan¹,*,
Shanna L. Bowman³,⁴,*,
Ethan Jewett⁵,⁶,*,
Alessia Ranciaro¹,
Simon Thompson¹,
Yancy Lo¹,
Susanne P. Pfeifer⁷,
Jeffrey D. Jensen⁷,
Michael C. Campbell¹,⁸,
William Beggs¹,
Farhad Hormozdiari⁹,¹⁰,
Sununguko Wata Mpoloka¹¹,
Gaonyadiwe George Mokone¹²,
Thomas Nyambo¹³,
Dawit Wolde Meskel¹⁴,
Gurja Belay¹⁴,
Jake Haut, NISC Comparative Sequencing Program¹,†,
Harriet Rothschild¹⁵,
Leonard Zon¹⁵,¹⁶,
Yi Zhou¹⁵,¹⁷,
Michael A. Kovacs¹⁸,
Mai Xu¹⁸,
Tongwu Zhang¹⁸,
Kevin Bishop¹⁹,
Jason Sinclair¹⁹,
Cecilia Rivas²⁰,
Eugene Elliot²⁰,
Jiyeon Choi¹⁸,
Shengchao A. Li²¹,²²,
Belynda Hicks²¹,²²,
Shawn Burgess¹⁹,
Christian Abnet²¹,
Dawn E. Watkins-Chow²⁰,
Elena Oceana²³,
Yun S. Song⁵,⁶,²⁴,²⁵,²⁶,
Eleazar Eskin²⁷,
Kevin M. Brown¹⁸,
Michael S. Marks³,⁴,‡,
Stacie K. Loftus²⁰,‡,
William J. Pavan²⁰,‡,
Meredith Yeager²¹,²²,‡,
Stephen Chanock²¹,‡,
Sarah Tishkoff¹,²⁵,§

↵§Corresponding author. Email: tishkoff{at}mail.med.upenn.edu

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

↵* These authors contributed equally to this work.
↵‡ These authors contributed equally to this work.

↵† NISC Comparative Sequencing Program collaborators and affiliations are listed in the supplementary materials.

See allHide authors and affiliations

Science 12 Oct 2017:
eaan8433
DOI: 10.1126/science.aan8433

Nicholas G. Crawford

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Derek E. Kelly

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Genomics and Computational Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Matthew E. B. Hansen

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Marcia H. Beltrame

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Shaohua Fan

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Shanna L. Bowman

Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.Department of Pathology and Laboratory Medicine and Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Ethan Jewett

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Alessia Ranciaro

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Simon Thompson

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Yancy Lo

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Susanne P. Pfeifer

School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jeffrey D. Jensen

School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Michael C. Campbell

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Department of Biology, Howard University, Washington, DC 20059, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

William Beggs

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Farhad Hormozdiari

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Sununguko Wata Mpoloka

Department of Biological Sciences, University of Botswana, Gaborone, Botswana.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Gaonyadiwe George Mokone

Department. of Biomedical Sciences, University of Botswana School of Medicine, Gaborone, Botswana.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Thomas Nyambo

Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Dawit Wolde Meskel

Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Gurja Belay

Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jake Haut

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Harriet Rothschild

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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Leonard Zon

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.Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Yi Zhou

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.Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Michael A. Kovacs

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Mai Xu

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Tongwu Zhang

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Kevin Bishop

Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jason Sinclair

Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Cecilia Rivas

Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Eugene Elliot

Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jiyeon Choi

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Shengchao A. Li

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21701, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Belynda Hicks

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Shawn Burgess

Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Christian Abnet

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Dawn E. Watkins-Chow

Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Elena Oceana

Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Yun S. Song

Department of Electrical Engineering and Computer Sciences, University of California–Berkeley, Berkeley, CA 94704, USA.Department of Statistics, University of California–Berkeley, Berkeley, CA 94704, USA.Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.Department of Mathematics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Eleazar Eskin

Department of Computer Science, Department of Human Genetics, University of California–Los Angeles, Los Angeles, CA 90095, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Kevin M. Brown

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Michael S. Marks

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Stacie K. Loftus

Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

William J. Pavan

Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Meredith Yeager

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Stephen Chanock

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Sarah Tishkoff

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
For correspondence: tishkoff@mail.med.upenn.edu

Article
Figures & Data
Info & Metrics
eLetters
PDF

You are currently viewing the abstract.

View Full Text

Log in to view the full text

via AAAS login

AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Become a AAAS member
Activate account
Add journals
Account help

As a service to the community, this article is available for free. Existing users log in.

Become a AAAS member
Account help

Log in through your institution

More options

Purchase digital access to this article

Download and print this article for your personal scholarly, research, and educational use.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

This article has a correction. Please see:

Is corrected by - December 15, 2017

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 southern 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 UV response genes under selection in Eurasians.

View Full Text

Loci associated with skin pigmentation identified in African populations

This article has a correction. Please see:

Abstract

Article Tools