Nature Genetics
14, 400 - 405 (1996)
doi:10.1038/ng1296-400
Susceptible chiasmate configurations of chromosome 21 predispose to non−disjunction in both maternal meiosis I and meiosis IINeil E. Lamb1, Sallie B. Freeman1, Amanda Savage-Austin1, Dorothy Pettay1, Lisa Taft1, Jane Hersey1, Yuanchao Gu1, Joe Shen2, Denise Saker2, Kristen M. May3, Dimitris Avramopoulos4, Michael B. Petersen4, 5, Anni Hallberg5, Margareta Mikkelsen5, Terry J. Hassold2
& Stephanie L. Sherman1, 2, 6
1Department of Genetics and Molecular Medicine, Emory University School of Medicine, 1462 Clifton Rd., Atlanta, Georgia 30322, USA
2Department of Genetics and The Center for Human Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
3Division of Medical Genetics, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
4Department of Genetics, Institute of Child Health, Athens, Greece
5Danish Center for Human Genome Research, J.F. Kennedy Institute, Glostrup, Denmark
6, Correspondence should be addressed to S.S.1
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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