New Insights into Human Nondisjunction of Chromosome 21 in Oocytes 英文参考文献.docVIP

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New Insights into Human Nondisjunction of Chromosome 21 in Oocytes 英文参考文献.doc

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New Insights into Human Nondisjunction of Chromosome 21 in Oocytes 英文参考文献

NewInsightsintoHumanNondisjunctionof Chromosome21inOocytes TiffanyReneeOliver1*,EleanorFeingold2,3,KaiYu4,VivianCheung5,StuartTinker1 ,Maneesha Yadav-Shah1,NirupamaMasse1,StephanieL.Sherman1 1DepartmentofHumanGenetics,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,UnitedStatesofAmerica,2DepartmentofHumanGenetics,GraduateSchoolof PublicHealth,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,3DepartmentofBiostatistics,GraduateSchoolofPublicHealth,Universityof Pittsburgh,Pittsburgh,Pennsylvania, UnitedStatesofAmerica, 4DivisionofCancerEpidemiologyandGenetics,NationalCancerInstitute,Bethesda,Maryland,United StatesofAmerica,5DepartmentsofPediatricsandGenetics,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Nondisjunctionofchromosome21istheleadingcauseofDownsyndrome.Tworiskfactorsformaternalnondisjunctionof chromosome21areincreasedmaternalageandalteredrecombination.Inordertoprovidefurtherinsightonmechanisms underlyingnondisjunction,weexaminedtheassociationbetweenthesetwowellestablishedriskfactorsforchromosome 21nondisjunction.Inourapproach,shorttandemrepeatmarkersalongchromosome21weregenotypedinDNAcollected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunctionerrorandthematernalrecombinationprofile.Weanalyzed615maternalmeiosisIand253maternalmeiosis IIcasesstratifiedbymaternalage.TheexaminationofmeiosisIIerrors,thefirstofitstype,suggeststhatthepresenceofa singleexchangewithinthepericentromericregionof21qinteractswithmaternalage-relatedriskfactors.Thisobservation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternalageriskfactorsor2)apericentromericexchangeprotectsthebivalentagainstage-relatedriskfactorsallowing propersegregationofhomologuesatmeiosisI,butnotsegregationofsistersatmeiosisII.Incontrast,analysisofmaternal meiosisIerrorsindicatesthatasingletelomericexchangeimp