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.

Evolution of the Genomic Recombination Rate in Murid Rodents

“…There are small, albeit systematic, differences in male recombination rates estimated by cytological vs. genetic approaches (Sun et al 2004). Slight variations in the temporal loading of MLH1 onto DNA sites of recombinational repair could lead to uncounted recombination events by the method used here (Cheng et al 2009). On the other hand, genotyping error can induce artificial inflation in genetic linkage map lengths, especially in terminal chromosomal regions where flanking genotype data are absent (Broman et al 1998).…”

Recombination rate variation in closely related species

“…In comparing the same intervals between two closely related species in the absence of a genome sequence, one runs the risk of concluding increased divergence between species when in actuality, an inversion, insertion or deletion segregating in only one species is obscuring their comparable recombination rates. Third, recombination is variable within individuals and populations (Brooks and Marks, 1986;True et al, 1996;Carrington and Cullen, 2004;Neumann and Jeffreys, 2006;Graffelman et al, 2007;Coop et al, 2008;Paigen et al, 2008;Cheng et al, 2009;Dumont et al, 2009;Kong et al, 2010 etc). This variation may stem from actual heritable variation in recombination rates among individuals; variation within an individual among regions of its genome (as discussed above) or from environmental variation.…”

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…208). It is estimated that ϳ30% of Down syndrome births are as a result of lack of recombination between homologous chromosomes 21, as the most common chromosomes prone to lack crossover within fetal oocytes are chromosomes 21 and 22 (58). Furthermore, the distance from the centromere that the single cross-over are located also determines the risk of aneuploidy, and again appears independent of maternal age.…”