Altered DNA Methylation in Leukocytes with Trisomy 21 英文参考文献.docVIP

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Altered DNA Methylation in Leukocytes with Trisomy 21 英文参考文献.doc

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Altered DNA Methylation in Leukocytes with Trisomy 21 英文参考文献

AlteredDNAMethylationinLeukocyteswithTrisomy21 KristiKerkel1,NicoleSchupf2,3,KotaHatta4,DeborahPang2,MarthaSalas1,AlexanderKratz5 ,Mark Minden6,VundavalliMurty1,5,WarrenB.Zigman3,RichardP.Mayeux2,7,EdmundC.Jenkins3 ,Ali Torkamani8,NicholasJ.Schork8,WayneSilverman9,10,B.AnneCroy4,BenjaminTycko1,2,5* 1InstituteforCancerGenetics,ColumbiaUniversityMedicalCenter,NewYork,NewYork,UnitedStatesofAmerica,2TaubInstituteforResearchonAlzheimer’sdisease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America, 3Departments of Human Genetics, Epidemiology, and Psychiatry,InstituteforBasicResearchonDevelopmentalDisabilities,NewYork,NewYork,UnitedStatesofAmerica,4DepartmentsofAnatomyandCellBiologyand Microbiology and Immunology, Queen’s University, Kingston, Canada, 5Department of Pathology, Columbia University Medical Center, New York, New York, United States ofAmerica,6Department ofMedicalOncology andHematologyandDepartmentofMedicalBiophysics,University ofTorontoandPrincessMargaret Hospital, Toronto, Canada, 7Department of Neurology, Columbia University Medical Center, New York, New York, United States of America, 8Scripps Translational Science Institute,LaJolla,California,UnitedStatesofAmerica,9DepartmentofBehavioralPsychology,KennedyKriegerInstitute,Baltimore,Maryland,UnitedStatesofAmerica, 10DepartmentofPsychiatryandBehavioralSciences,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract TheprimaryabnormalityinDownsyndrome(DS),trisomy21,iswellknown;buthowthischromosomalgainproducesthe complexDSphenotype,includingimmunesystemdefects,isnotwellunderstood.WeprofiledDNAmethylationintotal peripheral blood leukocytes (PBL) and T-lymphocytes from adults with DS and normal controls and found gene-specific abnormalitiesofCpGmethylationinDS,withmanyofthedifferentiallymethylatedgeneshavingknownorpredictedroles in lymphocyte development and function. Validation of the microarray data by bisulfite sequen