Meiotic Recombination in Human Oocytes 英文参考文献.docVIP

MeioticRecombinationinHumanOocytes EdithY.Cheng1.,PatriciaA.Hunt2.,TheresaA.Naluai-Cecchini1,CorrineL.Fligner3,VictorY.Fujimoto4, TanyaL.Pasternack4,JackieM.Schwartz4,JodyE.Steinauer4,TraceyJ.Woodruff4,SheilaM.Cherry2, TerahA.Hansen2,RheaU.Vallente2,KarlW.Broman5,TerryJ.Hassold2* 1Department ofObstetricsandGynecology,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica, 2SchoolofMolecularBiosciences,Washington StateUniversity,Pullman,Washington,UnitedStatesofAmerica,3DepartmentofPathology,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica, 4Department of Obstetrics and Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, United States of America, 5DepartmentofBiostatisticsandMedicalInformatics,UniversityofWisconsin–Madison,Madison,Wisconsin,UnitedStatesofAmerica Abstract Studiesofhumantrisomiesindicatearemarkablerelationshipbetweenabnormalmeioticrecombinationandsubsequent nondisjunctionatmaternalmeiosisIorII.Specifically,failuretorecombineorrecombinationeventslocatedeithertoonear toortoofarfromthecentromerehavebeenlinkedtotheoriginofhumantrisomies.Itshouldbepossibletoidentifythese abnormal crossover configurations by using immunofluorescence methodology to directly examine the meiotic recombination process in the human female. Accordingly, we initiated studies of crossover-associated proteins (e.g., MLH1)inhumanfetaloocytestoanalyzetheirnumberanddistributiononnondisjunction-pronehumanchromosomesand, moregenerally,tocharacterizegenome-widelevelsofrecombinationinthehumanfemale.Ouranalysesindicatethatthe numberofMLH1fociislowerthanpredictedfromgeneticlinkageanalysis,butitslocalizationpatternconformstothat expectedforacrossover-associatedprotein.Instudiesofindividualchromosomes,ourobservationsprovideevidencefor the presence of ‘‘vulnerable’’ crossover configurations in the fetal oocyte, consistent with the idea that these are subsequentlytranslatedintonondisjunctionaleventsintheadultoo