Lookup NU author(s): Professor Mary Herbert,
Dr Lisa Lister
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In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond 35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is mediated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromosomes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms.
Author(s): Herbert M, Kalleas D, Cooney D, Lamb M, Lister L
Publication type: Review
Publication status: Published
Journal: Cold Spring Harbor Perspectives in Biology
Print publication date: 01/04/2015
ISSN (print): 2157-1422
ISSN (electronic): 1943-0264
PubMed id: 25833844