Gene Expression Profiling of Lymphoblasts from Autistic and Nonaffected Sib Pairs Altered Pathways in Neuronal Development and Steroid Biosynthesis 英文参考文献.docVIP

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Gene Expression Profiling of Lymphoblasts from Autistic and Nonaffected Sib Pairs Altered Pathways in Neuronal Development and Steroid Biosynthesis 英文参考文献.doc

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Gene Expression Profiling of Lymphoblasts from Autistic and Nonaffected Sib Pairs Altered Pathways in Neuronal Development and Steroid Biosynthesis 英文参考文献

GeneExpressionProfilingofLymphoblastsfromAutistic andNonaffectedSibPairs:AlteredPathwaysinNeuronal DevelopmentandSteroidBiosynthesis ValerieW.Hu1*,AnhThuNguyen1,KyungSoonKim1¤,MaraE.Steinberg1,TewaritSarachana1, MicheleA.Scully1,StevenJ.Soldin2,TruongLuu3,NormanH.Lee3 1DepartmentofBiochemistryandMolecularBiology,TheGeorgeWashingtonUniversityMedicalCenter,Washington,D.C.,UnitedStatesofAmerica,2Departmentsof Medicine, Pharmacology, and Oncology, Georgetown University Medical Center, Washington, D. C., United States of America, 3Department of Pharmacology and Physiology,TheGeorgeWashingtonUniversityMedicalCenter,Washington,D.C.,UnitedStatesofAmerica Abstract Despite the identification of numerous autism susceptibility genes, the pathobiology of autism remains unknown. The present‘‘case-control’’studytakesaglobalapproachtounderstandingthemolecularbasisofautismspectrumdisorders baseduponlarge-scalegeneexpressionprofiling.DNAmicroarrayanalyseswereconductedonlymphoblastoidcelllines fromover20sibpairsinwhichonesiblinghadadiagnosisofautismandtheotherwasnotaffectedinordertoidentify biochemical and signaling pathways which are differentially regulated in cells from autistic and nonautistic siblings. Bioinformatics and gene ontological analyses of the data implicate genes which are involved in nervous system development,inflammation,andcytoskeletalorganization,inadditiontogeneswhichmayberelevanttogastrointestinalor otherphysiologicalsymptomsoftenassociatedwithautism.Moreover,thedatafurthersuggeststhattheseprocessesmay be modulated by cholesterol/steroid metabolism, especially at the level of androgenic hormones. Elevation of male hormones,inturn,hasbeensuggestedasapossiblefactorinfluencingsusceptibilitytoautism,whichaffects,4timesas manymalesasfemales.Preliminarymetabolicprofilingofsteroidhormonesinlymphoblastoidcelllinesfromseveralpairs ofsiblingsrevealshigherlevelsoftestosteroneintheautisticsibling,whichisconsistentwiththeincreasedexpressionof twogenesinvolvedinthesteroidog