Meiotic recombination in human oocytes.
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.
Cheng
Edith Y
EY
Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America.
Hunt
Patricia A
PA
Naluai-Cecchini
Theresa A
TA
Fligner
Corrine L
CL
Fujimoto
Victor Y
VY
Pasternack
Tanya L
TL
Schwartz
Jackie M
JM
Steinauer
Jody E
JE
Woodruff
Tracey J
TJ
Cherry
Sheila M
SM
Hansen
Terah A
TA
Vallente
Rhea U
RU
Broman
Karl W
KW
Hassold
Terry J
TJ
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
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1