Genome-Wide Assessments Reveal Extremely High Levels of Polymorphism of Two Active Families of Mouse Endogenous Retroviral Elements 英文参考文献.docVIP

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Genome-Wide Assessments Reveal Extremely High Levels of Polymorphism of Two Active Families of Mouse Endogenous Retroviral Elements 英文参考文献.doc

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Genome-Wide Assessments Reveal Extremely High Levels of Polymorphism of Two Active Families of Mouse Endogenous Retroviral Elements 英文参考文献

Genome-WideAssessmentsRevealExtremelyHigh LevelsofPolymorphismofTwoActiveFamiliesofMouse EndogenousRetroviralElements YingZhang1,2,IrinaA.Maksakova1,2,LianeGagnier1,2,LouieN.vandeLagemaat1,2¤,DixieL.Mager1,2 * 1TerryFoxLaboratory,B.C.CancerResearchCentre,Vancouver,BritishColumbia,Canada,2DepartmentofMedicalGenetics,UniversityofBritishColumbia,Vancouver, BritishColumbia,Canada Abstract Endogenous retroviral elements (ERVs) in mice are significant genomic mutagens, causing ,10% of all reported spontaneousgermlinemutationsinlaboratorystrains.Themajorityofthesemutationsareduetoinsertionsoftwohigh copyERVfamilies,theIAPandETn/MusDelements.Thissignificantlevelofongoingretrotranspositionalactivitysuggests thatinbredmicearehighlyvariableincontentofthesetwoERVgroups.However,nocomprehensivegenome-widestudies have been performed to assess their level of polymorphism. Here we compared three test strains, for which sufficient genomic sequence is available, to each other and to the reference C57BL/6J genome and detected very high levels of insertionalpolymorphismforbothERVfamilies,withanestimatedfalsediscoveryrateofonly0.4%.Specifically,wefound thatatleast60%ofIAPand25%ofETn/MusDelementsdetectedinanystrainareabsentinoneormoreoftheotherthree strains.Thepolymorphicnatureofasetof40ETn/MusDelementsfoundwithingeneintronswasconfirmedusinggenomic PCRonDNAfromapanelofmousestrains.Forsomecases,wedetectedgene-splicingabnormalitiesinvolvingtheERVand obtainedadditionalevidencefordecreasedgeneexpressioninstrainscarryingtheinsertion.Intotal,weidentifiednearly 700polymorphicIAPorETn/MusDERVsorsolitaryLTRsthatresideingeneintrons,providingpotentialcandidatesthatmay contributetogeneexpressiondifferencesamongstrains.TheseextremelevelsofpolymorphismsuggestthatERVinsertions playasignificantroleingeneticdriftofmouselines. Citation:ZhangY,MaksakovaIA,GagnierL,vandeLagemaatLN,MagerDL(2008)Genome-WideAssessmentsRevealExtremelyHighLevelsofPolymorphismof TwoActiveFamiliesofMouseEndogenousRetroviralElemen