Loci associated with skin pigmentation identified in African populations,Science

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Loci associated with skin pigmentation identified in African populations
Science ( IF 56.9 ) Pub Date : 2017-11-17 00:00:00 , DOI: 10.1126/science.aan8433
Nicholas G. Crawford ₁ , Derek E. Kelly _{1,

2} , Matthew E. B. Hansen ₁ , Marcia H. Beltrame ₁ , Shaohua Fan ₁ , Shanna L. Bowman _{3,

4} , Ethan Jewett _{5,

6} , Alessia Ranciaro ₁ , Simon Thompson ₁ , Yancy Lo ₁ , Susanne P. Pfeifer ₇ , Jeffrey D. Jensen ₇ , Michael C. Campbell _{1,

8} , William Beggs ₁ , Farhad Hormozdiari _{9,

10} , Sununguko Wata Mpoloka ₁₁ , Gaonyadiwe George Mokone ₁₂ , Thomas Nyambo ₁₃ , Dawit Wolde Meskel ₁₄ , Gurja Belay ₁₄ , Jake Haut ₁ , Harriet Rothschild ₁₅ , Leonard Zon _{15,

16} , Yi Zhou _{15,

17} , Michael A. Kovacs ₁₈ , Mai Xu ₁₈ , Tongwu Zhang ₁₈ , Kevin Bishop ₁₉ , Jason Sinclair ₁₉ , Cecilia Rivas ₂₀ , Eugene Elliot ₂₀ , Jiyeon Choi ₁₈ , Shengchao A. Li _{21,

22} , Belynda Hicks _{21,

22} , Shawn Burgess ₁₉ , Christian Abnet ₂₁ , Dawn E. Watkins-Chow ₂₀ , Elena Oceana ₂₃ , Yun S. Song _{5,

6,

24,

25,

26} , Eleazar Eskin ₂₇ , Kevin M. Brown ₁₈ , Michael S. Marks _{3,

4} , Stacie K. Loftus ₂₀ , William J. Pavan ₂₀ , Meredith Yeager _{21,

22} , Stephen Chanock ₂₁ , Sarah A. Tishkoff _{1,

25} ,

Affiliation

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.
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.
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.
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Department of Biology, Howard University, Washington, DC 20059, USA.
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.
Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
Department of Biomedical Sciences, University of Botswana School of Medicine, Gaborone, Botswana.
Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia.
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.
Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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.
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, 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.
Department of Computer Science and Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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 nearSLC24A5,MFSD12,DDB1,TMEM138,OCA2, andHERC2that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant atSLC24A5was 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 thatMFSD12encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions nearDDB1/TMEM138correlate with expression of ultraviolet response genes under selection in Eurasians.

中文翻译：

在非洲人群中发现与皮肤色素沉着相关的基因座

尽管人类皮肤色素沉着范围广泛，但其在全球人群中的遗传基础知之甚少。检查种族多样化的非洲基因组，我们确定了与皮肤色素沉着显着相关的SLC24A5，MFSD12，DDB1，TMEM138，OCA2和HERC2中或附近的变体。遗传证据表明，来自非非洲人的基因流将atSLC24A5的轻度色素沉着变体引入了东非。在所有其他基因座上，非洲人与深色色素沉着相关的变异在南亚和澳大利亚-美拉尼西亚人群中的血统相同。功能分析表明，MFSD12编码一种溶酶体蛋白，该蛋白影响斑马鱼和小鼠的黑色素生成，

更新日期：2017-11-17

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