Repetitive Elements May Comprise Over Two-Thirds of the Human Genome 英文参考文献.docVIP

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Repetitive Elements May Comprise Over Two-Thirds of the Human Genome 英文参考文献.doc

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Repetitive Elements May Comprise Over Two-Thirds of the Human Genome 英文参考文献

RepetitiveElementsMayCompriseOverTwo-Thirdsof theHumanGenome A.P.JasondeKoning1,WanjunGu1¤,ToddA.Castoe1,MarkA.Batzer2,DavidD.Pollock1* 1DepartmentofBiochemistryandMolecularGenetics,SchoolofMedicine,UniversityofColorado,Aurora,Colorado,UnitedStatesofAmerica,2DepartmentofBiological Sciences,LouisianaStateUniversity,BatonRouge,Louisiana,UnitedStatesofAmerica Abstract Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences.Usingthisapproach,abouthalfofthehumangenomehasbeenpreviouslyidentifiedasTEsandlow-complexity repeats.Werecentlydevelopedahighlysensitivealternativedenovostrategy,P-clouds,thatinsteadsearchesforclustersof high-abundanceoligonucleotidesthatarerelatedinsequencespace(oligo‘‘clouds’’).WeshowherethatP-cloudspredicts .840Mbpofadditionalrepetitivesequencesinthehumangenome,thussuggestingthat66%–69%ofthehumangenome isrepetitiveorrepeat-derived.Toinvestigatethisremarkabledifference,weconducteddetailedanalysesoftheabilityof bothP-cloudsandacommonlyusedconventionalapproach,RepeatMasker(RM),todetectdifferentsizedfragmentsofthe highlyabundanthumanAluandMIRSINEs.RMcanhavesurprisinglylowsensitivityforevenmoderatelylongfragments,in contrasttoP-clouds,whichhasgoodsensitivitydowntosmallfragmentsizes(,25bp).Althoughshortfragmentshavea highintrinsicprobabilityofbeingfalsepositives,weperformedaprobabilisticannotationthatreflectsthisfact.Wefurther developed ‘‘element-specific’’ P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ,100Mbofpreviouslyunannotatedhumanelements.ESPestimatesofnewMIRsequencesareingoodagreementwith RM-basedpredictionsoftheamountthatRMmissed.Theseresultshighlighttheneedforcombined,probabilisticgenome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previouslybelieved. Citation: de Koning APJ, Gu W, Castoe TA, Batzer MA, Pollock DD (2011) Repetitive Elements May Comprise Over Two-Thirds