Examining Variation in Recombination Levels in the Human Female: A Test of the Production Line Hypothesis. R. Rowsey1, J. Gruhn1, K. Broman2, P. Hunt1, T. Hassold1 1) School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA; 2) Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI.
The most important risk factor for human aneuploidy is increasing maternal age, but the basis of this association remains unknown. Indeed, one of the earliest models of the maternal age effect - the Production Line Model proposed by Henderson and Edwards in 1968 - remains one of the most-cited explanations. The model has two key components: that the first oocytes to enter meiosis are the first ovulated, and that the first to enter meiosis have more recombination events (crossovers) than those that enter meiosis later in fetal life. Studies in rodents demonstrate that the first oocytes to enter meiosis are, indeed, the first to be ovulated, but the association between timing of meiotic entry and recombination levels has not been tested. We recently initiated molecular cytogenetic studies of second trimester human fetal ovaries, allowing us to directly examine the number and distribution of crossover-associated proteins in prophase stage oocytes. Our observations on over 8,000 oocytes from 191 ovarian samples demonstrate extraordinary variation in recombination within and among individuals, but provide no evidence of a difference in recombination levels between oocytes entering meiosis early or late in fetal life. Thus, our data provide the first direct test of the second tenet of the Production Line model and suggest that it does not provide a plausible explanation for the human maternal age effect, meaning that - 45 years after its introduction - we can finally conclude that the Production Line Model is not the basis for the maternal age effect on trisomy.
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