Quantitative Analysis of Focused A-To-I RNA Editing Sites by Ultra-High-Throughput Sequencing in Psychiatric Disorders 英文参考文献.docVIP

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Quantitative Analysis of Focused A-To-I RNA Editing Sites by Ultra-High-Throughput Sequencing in Psychiatric Disorders 英文参考文献.doc

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Quantitative Analysis of Focused A-To-I RNA Editing Sites by Ultra-High-Throughput Sequencing in Psychiatric Disorders 英文参考文献

QuantitativeAnalysisofFocusedA-To-IRNAEditingSites byUltra-High-ThroughputSequencinginPsychiatric Disorders HuZhu1,DanielJ.Urban1,JaredBlashka1,MatthewT.McPheeters1,WesleyK.Kroeze1, PiotrMieczkowski2,JamesC.Overholser3,GeorgeJ.Jurjus4,5,LesaDieter3,GouriJ.Mahajan6, GrazynaRajkowska6,ZefengWang1,PatrickF.Sullivan2,CraigA.Stockmeier4,6,BryanL.Roth1* 1DepartmentofPharmacology,UniversityofNorthCarolinaChapelHillMedicalSchool,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2DepartmentofGenetics, SchoolofMedicine,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3DepartmentofPsychology,CaseWesternReserveUniversity,Cleveland,Ohio,UnitedStatesof America,4DepartmentofPsychiatry,CaseWesternReserveUniversity,Cleveland,Ohio,UnitedStatesofAmerica,5DepartmentofPsychiatry,LouisStokesClevelandVA MedicalCenter,Cleveland,Ohio,UnitedStatesofAmerica,6CenterforPsychiatricNeuroscience,DepartmentofPsychiatryandHumanBehavior,UniversityofMississippi MedicalCenter,Jackson,Mississippi,UnitedStatesofAmerica Abstract A-to-I RNA editing is a post-transcriptional modification of single nucleotides in RNA by adenosine deamination, which thereby diversifies the gene products encoded in the genome. Thousands of potential RNA editing sites have been identifiedbyrecentstudies(e.g.seeLietal,Science2009);however,onlyahandfulofthesesiteshavebeenindependently confirmed.Here,wesystematicallyandquantitativelyexamined109putativecodingregionA-to-IRNAeditingsitesinthree setsofnormalhumanbrainsamplesbyultra-high-throughputsequencing(uHTS).Fortyof109putativesites,including25 previouslyconfirmedsites,werevalidatedastrulyeditedinourbrainsamples,suggestinganoverestimationofA-to-IRNA editingintheseputativesitesbyLietal(2009).ToevaluateRNAeditinginhumandisease,weanalyzed29oftheconfirmed sitesinsubjectswithmajordepressivedisorderandschizophreniausinguHTS.Instrikingcontrasttomanypriorstudies,we didnotfindsignificantalterationsinthefrequencyofRNAeditingatanyoftheeditingsitesinsamplesfromthesepatients, including within the