资源描述：
《A_De_Novo_Paradigm_for_Mental_Retardation_LisenkaELMVissers_NatGenet_2010》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
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
