A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway
Identifieur interne : 004860 ( Main/Exploration ); précédent : 004859; suivant : 004861A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway
Auteurs : Christian Praetorius [Islande] ; Christine Grill [Islande] ; Simon N. Stacey [Islande] ; Alexander M. Metcalf [Australie] ; David U. Gorkin [États-Unis] ; Kathleen C. Robinson [États-Unis] ; Eric Van Otterloo [États-Unis] ; Reuben S. Q. Kim [Australie] ; Kristin Bergsteinsdottir [Islande] ; Margret H. Ogmundsdottir [Islande] ; Erna Magnusdottir [Islande] ; Pravin J. Mishra [États-Unis] ; Sean R. Davis [États-Unis] ; Theresa Guo [États-Unis] ; M. Raza Zaidi [États-Unis] ; Agnar S. Helgason [Islande] ; Martin I. Sigurdsson [Islande] ; Paul S. Melzer [États-Unis] ; Glenn Merlino [États-Unis] ; Valerie Petit [France] ; Lionel Larue [France] ; Stacie K. Loftus [États-Unis] ; David R. Adams [États-Unis] ; Ulduz Sobhiafshar [Turquie] ; N. C. Tolga Emre [Turquie] ; William J. Pavan [États-Unis] ; Robert Cornell [États-Unis] ; Aaron G. Smith [Australie] ; Andrew S. Mccallion [États-Unis] ; David E. Fisher [États-Unis] ; Kari Stefansson [Islande] ; Richard A. Sturm [Australie] ; Eiríkur Steingrímsson [Islande]Source :
- Cell [ 0092-8674 ] ; 2013.
Abstract
Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect non-coding regions. A single nucleotide polymorphism (SNP) within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes and brown hair color. Here we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor which together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a non-coding polymorphism that affects a phenotype by modulating a developmental gene regulatory network.
Url:
DOI: 10.1016/j.cell.2013.10.022
PubMed: 24267888
PubMed Central: 3873608
Affiliations:
- Australie, France, Islande, Turquie, États-Unis
- Iowa, Maryland, Massachusetts, Île-de-France
- Iowa City
- Université de l'Iowa
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Kim</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Bergsteinsdottir, Kristin" sort="Bergsteinsdottir, Kristin" uniqKey="Bergsteinsdottir K" first="Kristin" last="Bergsteinsdottir">Kristin Bergsteinsdottir</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Ogmundsdottir, Margret H" sort="Ogmundsdottir, Margret H" uniqKey="Ogmundsdottir M" first="Margret H." last="Ogmundsdottir">Margret H. Ogmundsdottir</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Magnusdottir, Erna" sort="Magnusdottir, Erna" uniqKey="Magnusdottir E" first="Erna" last="Magnusdottir">Erna Magnusdottir</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Mishra, Pravin J" sort="Mishra, Pravin J" uniqKey="Mishra P" first="Pravin J." last="Mishra">Pravin J. 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Helgason</name><affiliation wicri:level="1"><nlm:aff id="A2">Decode Genetics, Sturlugata 8, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Decode Genetics, Sturlugata 8, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Sigurdsson, Martin I" sort="Sigurdsson, Martin I" uniqKey="Sigurdsson M" first="Martin I." last="Sigurdsson">Martin I. Sigurdsson</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Melzer, Paul S" sort="Melzer, Paul S" uniqKey="Melzer P" first="Paul S." last="Melzer">Paul S. Melzer</name><affiliation wicri:level="2"><nlm:aff id="A10">Genetics Branch, National Cancer Institute, Bldg 37, Room 6138, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetics Branch, National Cancer Institute, Bldg 37, Room 6138, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Merlino, Glenn" sort="Merlino, Glenn" uniqKey="Merlino G" first="Glenn" last="Merlino">Glenn Merlino</name><affiliation wicri:level="2"><nlm:aff id="A9">Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Petit, Valerie" sort="Petit, Valerie" uniqKey="Petit V" first="Valerie" last="Petit">Valerie Petit</name><affiliation wicri:level="3"><nlm:aff id="A11">Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Larue, Lionel" sort="Larue, Lionel" uniqKey="Larue L" first="Lionel" last="Larue">Lionel Larue</name><affiliation wicri:level="3"><nlm:aff id="A11">Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Loftus, Stacie K" sort="Loftus, Stacie K" uniqKey="Loftus S" first="Stacie K." last="Loftus">Stacie K. Loftus</name><affiliation wicri:level="2"><nlm:aff id="A12">Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Adams, David R" sort="Adams, David R" uniqKey="Adams D" first="David R." last="Adams">David R. Adams</name><affiliation wicri:level="2"><nlm:aff id="A13">Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sobhiafshar, Ulduz" sort="Sobhiafshar, Ulduz" uniqKey="Sobhiafshar U" first="Ulduz" last="Sobhiafshar">Ulduz Sobhiafshar</name><affiliation wicri:level="1"><nlm:aff id="A14">Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul, Turkey</nlm:aff><country xml:lang="fr">Turquie</country><wicri:regionArea>Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Emre, N C Tolga" sort="Emre, N C Tolga" uniqKey="Emre N" first="N. C. Tolga" last="Emre">N. C. Tolga Emre</name><affiliation wicri:level="1"><nlm:aff id="A14">Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul, Turkey</nlm:aff><country xml:lang="fr">Turquie</country><wicri:regionArea>Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Pavan, William J" sort="Pavan, William J" uniqKey="Pavan W" first="William J." last="Pavan">William J. Pavan</name><affiliation wicri:level="2"><nlm:aff id="A12">Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Cornell, Robert" sort="Cornell, Robert" uniqKey="Cornell R" first="Robert" last="Cornell">Robert Cornell</name><affiliation wicri:level="4"><nlm:aff id="A7">Anatomy and Cell Biology, University of Iowa, 357 Medical Research Center, Iowa City, IA 52242-1101, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Anatomy and Cell Biology, University of Iowa, 357 Medical Research Center, Iowa City, IA 52242-1101</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Smith, Aaron G" sort="Smith, Aaron G" uniqKey="Smith A" first="Aaron G." last="Smith">Aaron G. Smith</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Mccallion, Andrew S" sort="Mccallion, Andrew S" uniqKey="Mccallion A" first="Andrew S." last="Mccallion">Andrew S. Mccallion</name><affiliation wicri:level="2"><nlm:aff id="A4">McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Fisher, David E" sort="Fisher, David E" uniqKey="Fisher D" first="David E." last="Fisher">David E. Fisher</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation wicri:level="1"><nlm:aff id="A2">Decode Genetics, Sturlugata 8, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Decode Genetics, Sturlugata 8, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Sturm, Richard A" sort="Sturm, Richard A" uniqKey="Sturm R" first="Richard A." last="Sturm">Richard A. Sturm</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Steingrimsson, Eirikur" sort="Steingrimsson, Eirikur" uniqKey="Steingrimsson E" first="Eiríkur" last="Steingrímsson">Eiríkur Steingrímsson</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24267888</idno><idno type="pmc">3873608</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873608</idno><idno type="RBID">PMC:3873608</idno><idno type="doi">10.1016/j.cell.2013.10.022</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">001D44</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D44</idno><idno type="wicri:Area/Pmc/Curation">001C00</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001C00</idno><idno type="wicri:Area/Pmc/Checkpoint">001C80</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001C80</idno><idno type="wicri:Area/Ncbi/Merge">001598</idno><idno type="wicri:Area/Ncbi/Curation">001598</idno><idno type="wicri:Area/Ncbi/Checkpoint">001598</idno><idno type="wicri:doubleKey">0092-8674:2013:Praetorius C:a:polymorphism:in</idno><idno type="wicri:Area/Main/Merge">004983</idno><idno type="wicri:Area/Main/Curation">004860</idno><idno type="wicri:Area/Main/Exploration">004860</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway</title><author><name sortKey="Praetorius, Christian" sort="Praetorius, Christian" uniqKey="Praetorius C" first="Christian" last="Praetorius">Christian Praetorius</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Grill, Christine" sort="Grill, Christine" uniqKey="Grill C" first="Christine" last="Grill">Christine Grill</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Stacey, Simon N" sort="Stacey, Simon N" uniqKey="Stacey S" first="Simon N." last="Stacey">Simon N. Stacey</name><affiliation wicri:level="1"><nlm:aff id="A2">Decode Genetics, Sturlugata 8, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Decode Genetics, Sturlugata 8, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Metcalf, Alexander M" sort="Metcalf, Alexander M" uniqKey="Metcalf A" first="Alexander M." last="Metcalf">Alexander M. Metcalf</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Gorkin, David U" sort="Gorkin, David U" uniqKey="Gorkin D" first="David U." last="Gorkin">David U. Gorkin</name><affiliation wicri:level="2"><nlm:aff id="A4">McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205</wicri:regionArea><wicri:noRegion>Maryland 21205</wicri:noRegion></affiliation></author><author><name sortKey="Robinson, Kathleen C" sort="Robinson, Kathleen C" uniqKey="Robinson K" first="Kathleen C." last="Robinson">Kathleen C. Robinson</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Van Otterloo, Eric" sort="Van Otterloo, Eric" uniqKey="Van Otterloo E" first="Eric" last="Van Otterloo">Eric Van Otterloo</name><affiliation wicri:level="4"><nlm:aff id="A7">Anatomy and Cell Biology, University of Iowa, 357 Medical Research Center, Iowa City, IA 52242-1101, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Anatomy and Cell Biology, University of Iowa, 357 Medical Research Center, Iowa City, IA 52242-1101</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Kim, Reuben S Q" sort="Kim, Reuben S Q" uniqKey="Kim R" first="Reuben S. Q." last="Kim">Reuben S. Q. Kim</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Bergsteinsdottir, Kristin" sort="Bergsteinsdottir, Kristin" uniqKey="Bergsteinsdottir K" first="Kristin" last="Bergsteinsdottir">Kristin Bergsteinsdottir</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Ogmundsdottir, Margret H" sort="Ogmundsdottir, Margret H" uniqKey="Ogmundsdottir M" first="Margret H." last="Ogmundsdottir">Margret H. Ogmundsdottir</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Magnusdottir, Erna" sort="Magnusdottir, Erna" uniqKey="Magnusdottir E" first="Erna" last="Magnusdottir">Erna Magnusdottir</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Mishra, Pravin J" sort="Mishra, Pravin J" uniqKey="Mishra P" first="Pravin J." last="Mishra">Pravin J. Mishra</name><affiliation wicri:level="2"><nlm:aff id="A9">Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Davis, Sean R" sort="Davis, Sean R" uniqKey="Davis S" first="Sean R." last="Davis">Sean R. Davis</name><affiliation wicri:level="2"><nlm:aff id="A10">Genetics Branch, National Cancer Institute, Bldg 37, Room 6138, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetics Branch, National Cancer Institute, Bldg 37, Room 6138, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Guo, Theresa" sort="Guo, Theresa" uniqKey="Guo T" first="Theresa" last="Guo">Theresa Guo</name><affiliation wicri:level="2"><nlm:aff id="A9">Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zaidi, M Raza" sort="Zaidi, M Raza" uniqKey="Zaidi M" first="M. Raza" last="Zaidi">M. Raza Zaidi</name><affiliation wicri:level="2"><nlm:aff id="A9">Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Helgason, Agnar S" sort="Helgason, Agnar S" uniqKey="Helgason A" first="Agnar S." last="Helgason">Agnar S. Helgason</name><affiliation wicri:level="1"><nlm:aff id="A2">Decode Genetics, Sturlugata 8, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Decode Genetics, Sturlugata 8, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Sigurdsson, Martin I" sort="Sigurdsson, Martin I" uniqKey="Sigurdsson M" first="Martin I." last="Sigurdsson">Martin I. Sigurdsson</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Melzer, Paul S" sort="Melzer, Paul S" uniqKey="Melzer P" first="Paul S." last="Melzer">Paul S. Melzer</name><affiliation wicri:level="2"><nlm:aff id="A10">Genetics Branch, National Cancer Institute, Bldg 37, Room 6138, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetics Branch, National Cancer Institute, Bldg 37, Room 6138, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Merlino, Glenn" sort="Merlino, Glenn" uniqKey="Merlino G" first="Glenn" last="Merlino">Glenn Merlino</name><affiliation wicri:level="2"><nlm:aff id="A9">Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Room 5002, 37 Convent Drive, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Petit, Valerie" sort="Petit, Valerie" uniqKey="Petit V" first="Valerie" last="Petit">Valerie Petit</name><affiliation wicri:level="3"><nlm:aff id="A11">Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Larue, Lionel" sort="Larue, Lionel" uniqKey="Larue L" first="Lionel" last="Larue">Lionel Larue</name><affiliation wicri:level="3"><nlm:aff id="A11">Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, 91405</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Loftus, Stacie K" sort="Loftus, Stacie K" uniqKey="Loftus S" first="Stacie K." last="Loftus">Stacie K. Loftus</name><affiliation wicri:level="2"><nlm:aff id="A12">Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Adams, David R" sort="Adams, David R" uniqKey="Adams D" first="David R." last="Adams">David R. Adams</name><affiliation wicri:level="2"><nlm:aff id="A13">Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Sobhiafshar, Ulduz" sort="Sobhiafshar, Ulduz" uniqKey="Sobhiafshar U" first="Ulduz" last="Sobhiafshar">Ulduz Sobhiafshar</name><affiliation wicri:level="1"><nlm:aff id="A14">Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul, Turkey</nlm:aff><country xml:lang="fr">Turquie</country><wicri:regionArea>Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Emre, N C Tolga" sort="Emre, N C Tolga" uniqKey="Emre N" first="N. C. Tolga" last="Emre">N. C. Tolga Emre</name><affiliation wicri:level="1"><nlm:aff id="A14">Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul, Turkey</nlm:aff><country xml:lang="fr">Turquie</country><wicri:regionArea>Laboratory of Genome Regulation, Department of Molecular Biology and Genetics, BoğaziçI University, Bebek 34342, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Pavan, William J" sort="Pavan, William J" uniqKey="Pavan W" first="William J." last="Pavan">William J. Pavan</name><affiliation wicri:level="2"><nlm:aff id="A12">Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Cornell, Robert" sort="Cornell, Robert" uniqKey="Cornell R" first="Robert" last="Cornell">Robert Cornell</name><affiliation wicri:level="4"><nlm:aff id="A7">Anatomy and Cell Biology, University of Iowa, 357 Medical Research Center, Iowa City, IA 52242-1101, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Anatomy and Cell Biology, University of Iowa, 357 Medical Research Center, Iowa City, IA 52242-1101</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Smith, Aaron G" sort="Smith, Aaron G" uniqKey="Smith A" first="Aaron G." last="Smith">Aaron G. Smith</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Mccallion, Andrew S" sort="Mccallion, Andrew S" uniqKey="Mccallion A" first="Andrew S." last="Mccallion">Andrew S. Mccallion</name><affiliation wicri:level="2"><nlm:aff id="A4">McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Fisher, David E" sort="Fisher, David E" uniqKey="Fisher D" first="David E." last="Fisher">David E. Fisher</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation wicri:level="1"><nlm:aff id="A2">Decode Genetics, Sturlugata 8, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Decode Genetics, Sturlugata 8, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Sturm, Richard A" sort="Sturm, Richard A" uniqKey="Sturm R" first="Richard A." last="Sturm">Richard A. Sturm</name><affiliation wicri:level="1"><nlm:aff id="A3">Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072</wicri:regionArea><wicri:noRegion>Qld 4072</wicri:noRegion></affiliation></author><author><name sortKey="Steingrimsson, Eirikur" sort="Steingrimsson, Eirikur" uniqKey="Steingrimsson E" first="Eiríkur" last="Steingrímsson">Eiríkur Steingrímsson</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland</nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik</wicri:regionArea><wicri:noRegion>101 Reykjavik</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell</title><idno type="ISSN">0092-8674</idno><idno type="eISSN">1097-4172</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect non-coding regions. A single nucleotide polymorphism (SNP) within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes and brown hair color. Here we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor which together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a non-coding polymorphism that affects a phenotype by modulating a developmental gene regulatory network.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Islande</li><li>Turquie</li><li>États-Unis</li></country><region><li>Iowa</li><li>Maryland</li><li>Massachusetts</li><li>Île-de-France</li></region><settlement><li>Iowa City</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="Islande"><noRegion><name sortKey="Praetorius, Christian" sort="Praetorius, Christian" uniqKey="Praetorius C" first="Christian" last="Praetorius">Christian Praetorius</name></noRegion><name sortKey="Bergsteinsdottir, Kristin" sort="Bergsteinsdottir, Kristin" uniqKey="Bergsteinsdottir K" first="Kristin" last="Bergsteinsdottir">Kristin Bergsteinsdottir</name><name sortKey="Grill, Christine" sort="Grill, Christine" uniqKey="Grill C" first="Christine" last="Grill">Christine Grill</name><name sortKey="Helgason, Agnar S" sort="Helgason, Agnar S" uniqKey="Helgason A" first="Agnar S." last="Helgason">Agnar S. Helgason</name><name sortKey="Magnusdottir, Erna" sort="Magnusdottir, Erna" uniqKey="Magnusdottir E" first="Erna" last="Magnusdottir">Erna Magnusdottir</name><name sortKey="Ogmundsdottir, Margret H" sort="Ogmundsdottir, Margret H" uniqKey="Ogmundsdottir M" first="Margret H." last="Ogmundsdottir">Margret H. Ogmundsdottir</name><name sortKey="Sigurdsson, Martin I" sort="Sigurdsson, Martin I" uniqKey="Sigurdsson M" first="Martin I." last="Sigurdsson">Martin I. Sigurdsson</name><name sortKey="Stacey, Simon N" sort="Stacey, Simon N" uniqKey="Stacey S" first="Simon N." last="Stacey">Simon N. Stacey</name><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><name sortKey="Steingrimsson, Eirikur" sort="Steingrimsson, Eirikur" uniqKey="Steingrimsson E" first="Eiríkur" last="Steingrímsson">Eiríkur Steingrímsson</name></country><country name="Australie"><noRegion><name sortKey="Metcalf, Alexander M" sort="Metcalf, Alexander M" uniqKey="Metcalf A" first="Alexander M." last="Metcalf">Alexander M. Metcalf</name></noRegion><name sortKey="Kim, Reuben S Q" sort="Kim, Reuben S Q" uniqKey="Kim R" first="Reuben S. Q." last="Kim">Reuben S. Q. Kim</name><name sortKey="Kim, Reuben S Q" sort="Kim, Reuben S Q" uniqKey="Kim R" first="Reuben S. Q." last="Kim">Reuben S. Q. Kim</name><name sortKey="Smith, Aaron G" sort="Smith, Aaron G" uniqKey="Smith A" first="Aaron G." last="Smith">Aaron G. Smith</name><name sortKey="Smith, Aaron G" sort="Smith, Aaron G" uniqKey="Smith A" first="Aaron G." last="Smith">Aaron G. Smith</name><name sortKey="Sturm, Richard A" sort="Sturm, Richard A" uniqKey="Sturm R" first="Richard A." last="Sturm">Richard A. Sturm</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Gorkin, David U" sort="Gorkin, David U" uniqKey="Gorkin D" first="David U." last="Gorkin">David U. Gorkin</name></region><name sortKey="Adams, David R" sort="Adams, David R" uniqKey="Adams D" first="David R." last="Adams">David R. Adams</name><name sortKey="Cornell, Robert" sort="Cornell, Robert" uniqKey="Cornell R" first="Robert" last="Cornell">Robert Cornell</name><name sortKey="Davis, Sean R" sort="Davis, Sean R" uniqKey="Davis S" first="Sean R." last="Davis">Sean R. Davis</name><name sortKey="Fisher, David E" sort="Fisher, David E" uniqKey="Fisher D" first="David E." last="Fisher">David E. Fisher</name><name sortKey="Gorkin, David U" sort="Gorkin, David U" uniqKey="Gorkin D" first="David U." last="Gorkin">David U. Gorkin</name><name sortKey="Guo, Theresa" sort="Guo, Theresa" uniqKey="Guo T" first="Theresa" last="Guo">Theresa Guo</name><name sortKey="Loftus, Stacie K" sort="Loftus, Stacie K" uniqKey="Loftus S" first="Stacie K." last="Loftus">Stacie K. Loftus</name><name sortKey="Mccallion, Andrew S" sort="Mccallion, Andrew S" uniqKey="Mccallion A" first="Andrew S." last="Mccallion">Andrew S. Mccallion</name><name sortKey="Melzer, Paul S" sort="Melzer, Paul S" uniqKey="Melzer P" first="Paul S." last="Melzer">Paul S. Melzer</name><name sortKey="Merlino, Glenn" sort="Merlino, Glenn" uniqKey="Merlino G" first="Glenn" last="Merlino">Glenn Merlino</name><name sortKey="Mishra, Pravin J" sort="Mishra, Pravin J" uniqKey="Mishra P" first="Pravin J." last="Mishra">Pravin J. Mishra</name><name sortKey="Pavan, William J" sort="Pavan, William J" uniqKey="Pavan W" first="William J." last="Pavan">William J. Pavan</name><name sortKey="Robinson, Kathleen C" sort="Robinson, Kathleen C" uniqKey="Robinson K" first="Kathleen C." last="Robinson">Kathleen C. Robinson</name><name sortKey="Van Otterloo, Eric" sort="Van Otterloo, Eric" uniqKey="Van Otterloo E" first="Eric" last="Van Otterloo">Eric Van Otterloo</name><name sortKey="Zaidi, M Raza" sort="Zaidi, M Raza" uniqKey="Zaidi M" first="M. Raza" last="Zaidi">M. Raza Zaidi</name></country><country name="France"><region name="Île-de-France"><name sortKey="Petit, Valerie" sort="Petit, Valerie" uniqKey="Petit V" first="Valerie" last="Petit">Valerie Petit</name></region><name sortKey="Larue, Lionel" sort="Larue, Lionel" uniqKey="Larue L" first="Lionel" last="Larue">Lionel Larue</name></country><country name="Turquie"><noRegion><name sortKey="Sobhiafshar, Ulduz" sort="Sobhiafshar, Ulduz" uniqKey="Sobhiafshar U" first="Ulduz" last="Sobhiafshar">Ulduz Sobhiafshar</name></noRegion><name sortKey="Emre, N C Tolga" sort="Emre, N C Tolga" uniqKey="Emre N" first="N. C. Tolga" last="Emre">N. C. Tolga Emre</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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