Genetic Networks of Liver Metabolism Revealed by Integration of Metabolic and Transcriptional Profiling 英文参考文献.docVIP

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Genetic Networks of Liver Metabolism Revealed by Integration of Metabolic and Transcriptional Profiling 英文参考文献.doc

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Genetic Networks of Liver Metabolism Revealed by Integration of Metabolic and Transcriptional Profiling 英文参考文献

GeneticNetworksofLiverMetabolismRevealedby IntegrationofMetabolicandTranscriptionalProfiling ChristineT.Ferrara1,2,3*,PingWang4,EliasChaibubNeto4,RobertD.Stevens1,JamesR.Bain1,BrettR. Wenner1,OlgaR.Ilkayeva1,MarkP.Keller2,3,DanielA.Blasiole2,3,ChristinaKendziorski5,BrianS. Yandell4,6,ChristopherB.Newgard1*,AlanD.Attie2* 1SarahW.StedmanNutritionandMetabolismCenter,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica,2DepartmentofPharmacology andCancerBiology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica,3DepartmentofBiochemistry,UniversityofWisconsin,Madison, Wisconsin,UnitedStatesofAmerica,4DepartmentofStatistics,UniversityofWisconsin,Madison,Wisconsin,UnitedStatesofAmerica,5DepartmentofBiostatisticsand MedicalInformatics,UniversityofWisconsin,Madison,Wisconsin,UnitedStatesofAmerica,6DepartmentofHorticulture,UniversityofWisconsin,Madison,Wisconsin, UnitedStatesofAmerica Abstract Althoughnumerousquantitativetraitloci(QTL)influencingdisease-relatedphenotypeshavebeendetectedthroughgene mapping and positional cloning, identification of the individual gene(s) and molecular pathways leading to those phenotypesisoftenelusive.Onewaytoimproveunderstandingofgeneticarchitectureistoclassifyphenotypesingreater depthbyincludingtranscriptionalandmetabolicprofiling.Inthecurrentstudy,wehavegeneratedandanalyzedmRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptinob/ob and the diabetes-susceptible BTBR leptinob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines). We show that liver metabolitesmaptodistinctgeneticregions,t