alexa Susceptible chiasmate configurations of chromosome 21 predispose to non−disjunction in both maternal meiosis I and meiosis II
Genetics & Molecular Biology

Genetics & Molecular Biology

Human Genetics & Embryology

Author(s): Neil E Lamb, Sallie B Freeman, Amanda SavageAustin, Dorothy Pettay, Lisa Taft, Jane Hersey, Yuanchao Gu, Joe Shen, Denise Saker, Terry J Hassold, Kristen M May, Dimitris Avramopoulos, Michael B Petersen, Anni Hallberg, Margareta Mikkelsen, Stephanie L Sherman

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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 21 q. 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 meioisis I.

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This article was published in Nature Genetics and referenced in Human Genetics & Embryology

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