title: Meiotic recombination in human oocytes.
abstract: Studies of human trisomies indicate a remarkable relationship between abnormal meiotic recombination and subsequent nondisjunction at maternal meiosis I or II. Specifically, failure to recombine or recombination events located either too near to or too far from the centromere have been linked to the origin of human trisomies. It should be possible to identify these 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) in human fetal oocytes to analyze their number and distribution on nondisjunction-prone human chromosomes and, more generally, to characterize genome-wide levels of recombination in the human female. Our analyses indicate that the number of MLH1 foci is lower than predicted from genetic linkage analysis, but its localization pattern conforms to that expected for a crossover-associated protein. In studies of individual chromosomes, our observations provide evidence for the presence of "vulnerable" crossover configurations in the fetal oocyte, consistent with the idea that these are subsequently translated into nondisjunctional events in the adult oocyte.
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Edith Y
authors.initials: EY
authors.lastname: Cheng
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Hunt
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Naluai-Cecchini
authors.forename: Corrine L
authors.initials: CL
authors.lastname: Fligner
authors.forename: Victor Y
authors.initials: VY
authors.lastname: Fujimoto
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Pasternack
authors.forename: Jackie M
authors.initials: JM
authors.lastname: Schwartz
authors.forename: Jody E
authors.initials: JE
authors.lastname: Steinauer
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Woodruff
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Cherry
authors.forename: Terah A
authors.initials: TA
authors.lastname: Hansen
authors.forename: Rhea U
authors.initials: RU
authors.lastname: Vallente
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Hassold
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002877:Chromosomes, Human / Q000235:genetics; D016001:Confidence Intervals; D005260:Female; D005333:Fetus / Q000166:cytology; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008540:Meiosis / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D021381:Protein Transport; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange / Q000235:genetics; D013997:Time Factors; D014314:Trisomy / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1