Selection of Target Sites for Mobile DNA Integration in the Human Genome 英文参考文献.docVIP

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Selection of Target Sites for Mobile DNA Integration in the Human Genome 英文参考文献.doc

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Selection of Target Sites for Mobile DNA Integration in the Human Genome 英文参考文献

SelectionofTargetSitesforMobileDNA IntegrationintheHumanGenome Charles Berry1,Sridhar Hannenhalli2,Jeremy Leipzig3,Frederic D.Bushman3* 1Department ofFamily andPreventiveMedicine,School ofMedicine,UniversityofCalifornia SanDiego, LaJolla,California,UnitedStates ofAmerica, 2Department of Genetics,UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,Pennsylvania, UnitedStatesofAmerica, 3DepartmentofMicrobiology, UniversityofPennsylvania SchoolofMedicine,Philadelphia,Pennsylvania,UnitedStatesofAmerica DNA sequences from retroviruses, retrotransposons, DNA transposons, and parvoviruses can all become integrated into the human genome. Accumulation of such sequences accounts for at least 40% of our genome today. These integrating elements are also of interest as gene-delivery vectors for human gene therapy. Here we present a comprehensivebioinformatic analysis ofintegration targetingbyHIV,MLV, ASLV,SFV,L1,SB, andAAV.Weuseda mathematicalmethodwhichallowedannotationofeachbasepairinthehumangenomeforitslikelihoodofhosting anintegrationeventbyeachtypeofelement,takingadvantageofmorethan200typesofgenomicannotation.This bioinformaticresourcedocumentsawealthofnewassociationsbetweengenomicfeaturesandintegrationtargeting. Thestudyalsorevealedthatthelengthofgenomicintervalsanalyzedstronglyaffectedtheconclusionsdrawn—thus, answeringthequestion‘‘Whatgenomicfeaturesaffectintegration?’’requirescarefullyspecifyingthelengthscaleof interest. Citation:BerryC,HannenhalliS,LeipzigJ,BushmanFD(2006)SelectionoftargetsitesformobileDNAintegrationinthehumangenome.PLoSComputBiol2(11):e157. doi:10.1371/journal.pcbi.0020157 DNA[3,4,19,20].LINE-relatedsequencescomprisefully20% of the human DNA [1,2]. LINEs are the only known class of Introduction The exons of human genes comprise only about 1.5% of the total genome sequence [1,2]. Fragments of genomic parasites—integrating viruses and transposons—comprise a much larger fraction, at least 40%. These elements are also highlydynamic—ne