Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Article numbere1003241
JournalPLoS Genetics
Volume9
Issue number2
Publication statusPublished - 2013
Peer-reviewedYes

External IDs

Scopus 84874768429
PubMed 23408896
PubMedCentral PMC3567145

Keywords

Keywords

  • Animals, Cell Cycle Proteins/genetics, Chromosomal Proteins, Non-Histone/genetics, Chromosome Pairing/genetics, Chromosome Segregation/genetics, Chromosomes/genetics, Female, Gene Dosage, Humans, Meiosis/genetics, Mice, Mutation, Nuclear Proteins/genetics, Phosphoproteins/genetics, Recombination, Genetic, Synaptonemal Complex/genetics