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《A_De_Novo_Paradigm_for_Mental_Retardation_LisenkaELMVissers_NatGenet_2010》由會(huì)員上傳分享，免費(fèi)在線閱讀，更多相關(guān)內(nèi)容在學(xué)術(shù)論文-天天文庫(kù)。
1、lettersAdenovoparadigmformentalretardationLisenkaELMVissers1,2,JoepdeLigt1,2,ChristianGilissen1,IreneJanssen1,MarloesSteehouwer1,PetradeVries1,BartvanLier1,PeerArts1,NienkeWieskamp1,MarisoldelRosario1,BregjeWMvanBon1,AlexanderHoischen1,BertBAdeVries1,HanGBrunner1,3&JorisAVeltman1,3Theper-gen
2、erationmutationrateinhumansishigh.whole-exome–sequencingapproachtotestthedenovomutationhypo-De?novomutationsmaycompensateforallelelossduetothesisinanunselectedcohortofindividualswithmentalretardation.severelyreducedfecundityincommonneurodevelopmentalWesequencedtheexomesoftencase-parenttrios.
3、Allcases,eightandpsychiatricdiseases,explainingamajorparadoxmalesandtwofemales,hadmoderatetoseverementalretardationinevolutionarygenetictheory.Hereweusedafamilyandanegativefamilyhistory.Clinicalevaluationdidnotleadtoabasedexomesequencingapproachtotestthisdenovosyndromicoretiologicdiagnosis(S
4、upplementaryNote).Priormutationhypothesisintenindividualswithunexplainedcytogeneticanalysisshowednormalchromosomes,andarray-basedmentalretardation.WeidentifiedandvalidateduniquegenomicprofilingdidnotrevealdenovoorotherCNVsassociatednon-synonymousdenovomutationsinninegenes.Sixofwithmentalreta
5、rdation.Inaddition,fragileXsyndromewasexcludedthese,identifiedinsixdifferentindividuals,arelikelytobebyFMR1repeatexpansionanalysis.Onaverage,weobtained3.1Gbpathogenicbasedongenefunction,evolutionaryconservationofmappablesequencedataperindividualafterexomeenrichmentandmutationimpact.Ourfindin
6、gsprovidestrongexperimental(37Mbofgenomicsequencetargeting~18,000genes)andsequenc-supportforadenovoparadigmformentalretardation.ingononequarterofaSOLiDsequencingslide(OnlineMethodsandTogetherwithdenovocopynumbervariation,denovopointSupplementaryTable1).Colorspacereadsweremappedtotherefer-mut
7、ationsoflargeeffectcouldexplainthemajorityofallencegenome.Onaverage,79.6%ofthebasesoriginatedfromthetar-mentalretardationcasesinthepopulation.getedexome,with90%ofthetargetedexonscoveredatleasttentimes.Themedianexoncoveragewas42-fold,indicatingthatt
