title: Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II.
abstract: The cause of non-disjunction of chromosome 21 remains largely unknown. Advanced maternal age is associated with both maternal meiosis I (MI) and meiosis II (MII) non-disjunction events. While reduced genetic recombination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with maternal MII errors to test the hypothesis that segregation at MII may also be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recombination that is largely restricted to proximal 21q. Thus, while absence of a proximal recombination appears to predispose to non-disjunction in MI, the presence of a proximal exchange predisposes to non-disjunction in MII. These findings profoundly affect our understanding of trisomy 21 as they suggest that virtually all maternal non-disjunction results from events occurring in meiosis I.
authors.affiliation: Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Lamb
authors.forename: S B
authors.initials: SB
authors.lastname: Freeman
authors.forename: A
authors.initials: A
authors.lastname: Savage-Austin
authors.forename: D
authors.initials: D
authors.lastname: Pettay
authors.forename: L
authors.initials: L
authors.lastname: Taft
authors.forename: J
authors.initials: J
authors.lastname: Hersey
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: D
authors.initials: D
authors.lastname: Saker
authors.forename: K M
authors.initials: KM
authors.lastname: May
authors.forename: D
authors.initials: D
authors.lastname: Avramopoulos
authors.forename: M B
authors.initials: MB
authors.lastname: Petersen
authors.forename: A
authors.initials: A
authors.lastname: Hallberg
authors.forename: M
authors.initials: M
authors.lastname: Mikkelsen
authors.forename: T J
authors.initials: TJ
authors.lastname: Hassold
authors.forename: S L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D000328:Adult; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000196:embryology / Q000235:genetics*; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus; D006801:Humans; D008297:Male; D008423:Maternal Age; D008540:Meiosis / Q000235:genetics*; D008957:Models, Genetic; D009630:Nondisjunction, Genetic; D011995:Recombination, Genetic