Journal article
Examining variation in recombination levels in the human female: a test of the production-line hypothesis
American journal of human genetics, Vol.95(1), pp.108-112
07/03/2014
Handle:
https://hdl.handle.net/2376/106091
PMCID: PMC4085639
PMID: 24995869
Abstract
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: (1) that the first oocytes to enter meiosis are the first ovulated and (2) that the first to enter meiosis have more recombination events (crossovers) than those that enter meiosis later in fetal life. Studies in rodents have demonstrated that the first oocytes to enter meiosis are indeed the first to be ovulated, but the association between the 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 in fetal life and those entering late in fetal life. Thus, our data provide a 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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Details
- Title
- Examining variation in recombination levels in the human female: a test of the production-line hypothesis
- Creators
- Ross Rowsey - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USAJennifer Gruhn - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USAKarl W Broman - Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USAPatricia A Hunt - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USATerry Hassold - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA. Electronic address: terryhassold@vetmed.wsu.edu
- Publication Details
- American journal of human genetics, Vol.95(1), pp.108-112
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- R01 ES013527 / NIEHS NIH HHS ES013527 / NIEHS NIH HHS HD21341 / NICHD NIH HHS R01 HD021341 / NICHD NIH HHS R37 HD021341 / NICHD NIH HHS T32 GM083864 / NIGMS NIH HHS
- Identifiers
- 99900546975501842
- Language
- English
- Resource Type
- Journal article