Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies 英文参考文献.docVIP

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Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies 英文参考文献.doc

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Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies 英文参考文献

PatternsofAncestry,SignaturesofNaturalSelection, andGeneticAssociationwithStatureinWesternAfrican Pygmies JosephP.Jarvis1,LauraB.Scheinfeldt1.,SameerSoi1.,CharlaLambert1.,LarssonOmberg2. BartFerwerda1,AlainFroment3,Jean-MarieBodo4,WilliamBeggs1,GabrielHoffman2,JasonMezey2,5, SarahA.Tishkoff1,6 , * 1Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2Department of Biological Statistics and Computational Biology,CornellUniversity,Ithaca,NewYork,UnitedStatesofAmerica,3UMR208,IRD-MNHN,Muse′edel’Homme,Paris,France,4MinisteredelaRechercheScientifique etdel’Innovation,Yaounde,Cameroon,5DepartmentofGeneticMedicine,WeillCornellMedicalCollege,NewYork,NewYork,UnitedStatesofAmerica,6Departmentof Biology,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract AfricanPygmygroupsshowadistinctivepatternofphenotypicvariation,includingshortstature,whichisthoughttoreflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed.Weinfergenome-wideancestry,scanforsignalsofpositiveselection,andperformtargetedgeneticassociation with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signalingpathways,aswellasimmunityandneuroendocrinesignalinginvolvedinreproductionandmetabolism.Themost striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60Mb. This region also includes the positional candidate genes DOCK3, which is known to be associatedwithheightvariationinEuropeans,andCISH,anegativeregulatorofcytokinesignalingknowntoinhibitgrowth hormone-stimulated STAT5 signaling. Finally, pathway analysi