Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior

Brenda Murdoch; Nichole Owen; Michelle Stevense; Helen Smith; So Nagaoka; Terry Hassold; Michael McKay; Huiling Xu; Jun Fu; Ekaterina Revenkova; Rolf Jessberger; Patricia Hunt

doi:10.1371/journal.pgen.1003241

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Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior

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Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior

Brenda Murdoch, Nichole Owen, Michelle Stevense, Helen Smith, So Nagaoka, Terry Hassold, Michael McKay, Huiling Xu, Jun Fu, Ekaterina Revenkova, …

PLoS genetics, Vol.9(2), pp.e1003241-e1003241

2013

DOI: https://doi.org/10.1371/journal.pgen.1003241

Handle:

https://hdl.handle.net/2376/106927

PMCID: PMC3567145

PMID: 23408896

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Abstract

Chromosomal Proteins, Non-Histone - metabolism

Humans

Cell Cycle Proteins - metabolism

Nuclear Proteins - metabolism

Gene Dosage

Phosphoproteins - genetics

Chromosome Pairing - genetics

Phosphoproteins - metabolism

Synaptonemal Complex - genetics

Chromosomal Proteins, Non-Histone - genetics

Chromosomes - ultrastructure

Meiosis - genetics

Animals

Chromosomes - genetics

Recombination, Genetic

Cell Cycle Proteins - genetics

Female

Mice

Mutation

Nuclear Proteins - genetics

Chromosome Segregation - genetics

Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC) and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

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Title: Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior
Creators: Brenda Murdoch - School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
Nichole Owen
Michelle Stevense
Helen Smith
So Nagaoka
Terry Hassold
Michael McKay
Huiling Xu
Jun Fu
Ekaterina Revenkova
Rolf Jessberger
Patricia Hunt
Publication Details: PLoS genetics, Vol.9(2), pp.e1003241-e1003241
Academic Unit: Center for Reproductive Biology; Molecular Biosciences, School of
Publisher: United States
Grant note: R01 ES013527 / NIEHS NIH HHS HD37502 / NICHD NIH HHS R01 HD037502 / NICHD NIH HHS T32 GM008336 / NIGMS NIH HHS ES013527 / NIEHS NIH HHS HD21341 / NICHD NIH HHS R56 ES013527 / NIEHS NIH HHS R01 GM062517 / NIGMS NIH HHS R01 HD021341 / NICHD NIH HHS GM062517 / NIGMS NIH HHS R37 HD021341 / NICHD NIH HHS
Identifiers: 99900546868001842
Language: English
Resource Type: Journal article