Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity 英文参考文献.docVIP

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Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity 英文参考文献.doc

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Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity 英文参考文献

GeneticandGenomicAnalysisofaFatMass TraitwithComplexInheritance RevealsMarkedSexSpecificity Susanna Wang1[,Nadir Yehya1[,Eric E.Schadt2[,Hui Wang3,Thomas A.Drake4,Aldons J.Lusis1,5,6,7* 1 Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 2 Rosetta Inpharmatics,Seattle,Washington,UnitedStatesofAmerica,3DepartmentofStatistics,CollegeofLettersandScience,UniversityofCaliforniaLosAngeles,LosAngeles, California,UnitedStatesofAmerica,4DepartmentofPathologyandLaboratoryMedicine,DavidGeffenSchoolofMedicine,UniversityofCaliforniaLosAngeles,LosAngeles, California,UnitedStatesofAmerica,5DepartmentofMedicine,DivisionofCardiology,DavidGeffenSchoolofMedicine,UniversityofCaliforniaLosAngeles,LosAngeles, California, United States of America, 6 Department of Microbiology, Immunology, and Molecular Genetics, College of Letters and Science, University of California Los Angeles,LosAngeles,California,UnitedStatesofAmerica,7MolecularBiologyInstitute,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica Theintegrationofexpressionprofilingwithlinkageanalysishasincreasinglybeenusedtoidentifygenesunderlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however,‘‘geneticalgenomic’’analyseshavenotyetaddressedthedegreetowhichtheirconclusionsareaffectedby sex.WeconstructedanddenselygenotypedalargeF2intercrossderivedfromtheinbredmousestrainsC57BL/6Jand C3H/HeJ on an apolipoprotein E null (ApoEà/à) background. This BXH.ApoEà/à population recapitulates several ‘‘metabolicsyndrome’’phenotypes.Thecrossconsistsof334animalsofbothsexes,allowingustospecificallytestfor the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significantproportionofwhicharesex-biased.Weusedtheseanalysestodissectthegeneticsofgonadalfatmass,a complextraitwithsex-specificregulation