Recent Assembly of an Imprinted Domain from Non-Imprinted Components 英文参考文献.docVIP

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Recent Assembly of an Imprinted Domain from Non-Imprinted Components 英文参考文献.doc

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Recent Assembly of an Imprinted Domain from Non-Imprinted Components 英文参考文献

RecentAssemblyofanImprintedDomain fromNon-ImprintedComponents Robert W. Rapkins1[,Tim Hore1[,Megan Smithwick2,Eleanor Ager3,Andrew J.Pask3,Marilyn B.Renfree3, Matthias Kohn4,Horst Hameister4,Robert D.Nicholls5,Janine E.Deakin1,Jennifer A.Marshall Graves1* 1AustralianResearchCouncilCenterforKangarooGenomicsandResearchSchoolofBiologicalSciences,AustralianNationalUniversity,Canberra,Australia,2Departmentof Genetics,LaTrobeUniversity,Melbourne,Australia,3DepartmentofZoology,UniversityofMelbourne,Melbourne,Australia,4DepartmentofMedicalGenetics,University ofUlm,Ulm,Germany,5DepartmentofPediatrics,Children’sHospitalofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Genomicimprinting,representingparent-specificexpressionofallelesatalocus,raisesmanyquestionsabouthow— andespeciallywhy—epigeneticsilencingofmammaliangenesevolved.Wepresentthefirstin-depthstudyofhowa humanimprinteddomainevolved,analyzingadomaincontainingseveralimprintedgenesthatareinvolvedinhuman disease. Using comparisons of orthologous genes in humans, marsupials, and the platypus, we discovered that the Prader-Willi/Angelman syndrome region on human Chromosome 15q was assembled only recently (105–180 million yearsago).ThisimprinteddomainaroseafteraregionbearingUBE3A(Angelmansyndrome)fusedwithanunlinked region bearing SNRPN (Prader-Willi syndrome), which had duplicated from the non-imprinted SNRPB/B9. This region independentlyacquiredseveralretroposedgenecopiesandarraysofsmallnucleolarRNAsfromdifferentpartsofthe genome.Intheiroriginalconfigurations,SNRPNandUBE3Aareexpressedfrombothalleles,implyingthatacquisition ofimprintingoccurredaftertheirrearrangementandrequiredtheevolutionofacontrollocus.Thus,theevolutionof imprintinginviviparousmammalsisongoing. Citation:RapkinsRW,HoreT,SmithwickM,AgerE,PaskAJ,etal.(2006)Recentassemblyofanimprinteddomainfromnon-imprintedcomponents.PLoSGenet2(10):e182. DOI:10.1371/journal.pgen.0020182 tomammals.Nonetheless,thegenecontentandarrangement ofhumanimprinteddomain