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Tytuł:
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Failure to recombine is a common feature of human oogenesis.
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Autorzy:
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Hassold T; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA. Electronic address: .
Maylor-Hagen H; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Wood A; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Gruhn J; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA; DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, NK 2200, Denmark.
Hoffmann E; DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, NK 2200, Denmark.
Broman KW; Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53706, USA.
Hunt P; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
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Źródło:
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American journal of human genetics [Am J Hum Genet] 2021 Jan 07; Vol. 108 (1), pp. 16-24. Date of Electronic Publication: 2020 Dec 10.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2008- : [Cambridge, MA] : Cell Press
Original Publication: Baltimore, American Society of Human Genetics.
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MeSH Terms:
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Oogenesis/*genetics
Recombination, Genetic/*genetics
Adolescent ; Adult ; Aneuploidy ; Chromosomes, Human, Pair 21/genetics ; Chromosomes, Human, Pair 22/genetics ; Female ; Humans ; Meiosis/genetics ; MutL Protein Homolog 1/genetics ; Nondisjunction, Genetic/genetics ; Oocytes/physiology ; Pregnancy ; Young Adult
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Grant Information:
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R01 ES013527 United States ES NIEHS NIH HHS; R37 HD021341 United States HD NICHD NIH HHS; Z01 HD008836 United States ImNIH Intramural NIH HHS; R24 HD000836 United States HD NICHD NIH HHS
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Contributed Indexing:
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Keywords: aneuploidy; exchangeless homologs; meiosis; oogenesis; recombination
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Substance Nomenclature:
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EC 3.6.1.3 (MutL Protein Homolog 1)
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Entry Date(s):
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Date Created: 20201211 Date Completed: 20210202 Latest Revision: 20210708
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Update Code:
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20240104
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PubMed Central ID:
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PMC7820622
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DOI:
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10.1016/j.ajhg.2020.11.010
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PMID:
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33306948
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Failure of homologous chromosomes to recombine is arguably the most important cause of human meiotic nondisjunction, having been linked to numerous autosomal and sex chromosome trisomies of maternal origin. However, almost all information on these "exchangeless" homologs has come from genetic mapping studies of trisomic conceptuses, so the incidence of this defect and its impact on gametogenesis are not clear. If oocytes containing exchangeless homologs are selected against during meiosis, the incidence may be much higher in developing germ cells than in zygotes. To address this, we initiated studies of exchangeless chromosomes in fetal ovarian samples from elective terminations of pregnancy. In total, we examined more than 7,000 oocytes from 160 tissue samples, scoring for the number of foci per cell of the crossover-associated protein MLH1. We identified a surprisingly high level of recombination failure, with more than 7% of oocytes containing at least one chromosome pair that lacked an MLH1 focus. Detailed analyses indicate striking chromosome-specific differences, with a preponderance of MLH1-less homologs involving chromosomes 21 or 22. Further, the effect was linked to the overall level of recombination in the cell, with the presence of one or two exchangeless chromosomes in a cell associated with a 10%-20% reduction in the total number of crossovers. This suggests individuals with lower rates of meiotic recombination are at an increased risk of producing aneuploid offspring.
(Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
