title: A model system for increased meiotic nondisjunction in older oocytes.
abstract: For at least 5% of all clinically recognized human pregnancies, meiotic segregation errors give rise to zygotes with the wrong number of chromosomes. Although most aneuploid fetuses perish in utero, trisomy in liveborns is the leading cause of mental retardation. A large percentage of human trisomies originate from segregation errors during female meiosis I; such errors increase in frequency with maternal age. Despite the clinical importance of age-dependent nondisjunction in humans, the underlying mechanisms remain largely unexplained. Efforts to recapitulate age-dependent nondisjunction in a mammalian experimental system have so far been unsuccessful. Here we provide evidence that Drosophila is an excellent model organism for investigating how oocyte aging contributes to meiotic nondisjunction. As in human oocytes, nonexchange homologs and bivalents with a single distal crossover in Drosophila oocytes are most susceptible to spontaneous nondisjunction during meiosis I. We show that in a sensitized genetic background in which sister chromatid cohesion is compromised, nonrecombinant X chromosomes become vulnerable to meiotic nondisjunction as Drosophila oocytes age. Our data indicate that the backup pathway that normally ensures proper segregation of achiasmate chromosomes deteriorates as Drosophila oocytes age and provide an intriguing paradigm for certain classes of age-dependent meiotic nondisjunction in humans.
authors.affiliation: Department of Biological Sciences, Dartmouth College, 6044 Gilman, Hanover, NH 03755, USA.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Jeffreys
authors.forename: Peter S
authors.initials: PS
authors.lastname: Burrage
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Bickel
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D005260:Female; D008540:Meiosis; D009154:Mutation / Q000235:genetics; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000166:cytology*; D011995:Recombination, Genetic / Q000235:genetics; D014960:X Chromosome / Q000235:genetics