title: Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.
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.
authors: School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
authors: Brenda
authors: B
authors: Murdoch
authors: Nichole
authors: N
authors: Owen
authors: Michelle
authors: M
authors: Stevense
authors: Helen
authors: H
authors: Smith
authors: So
authors: S
authors: Nagaoka
authors: Terry
authors: T
authors: Hassold
authors: Michael
authors: M
authors: McKay
authors: Huiling
authors: H
authors: Xu
authors: Jun
authors: J
authors: Fu
authors: Ekaterina
authors: E
authors: Revenkova
authors: Rolf
authors: R
authors: Jessberger
authors: Patricia
authors: P
authors: Hunt
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics / Q000648:ultrastructure; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013573:Synaptonemal Complex / Q000235:genetics; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000097722:Cohesins; C465863:Rec8 protein, mouse; C438001:Smc1l2 protein, mouse