© 1994 Oxford University Press
RESEARCH-ARTICLE |
Non-disjunction of chromosome 21 in maternal meiosis I: evidence for a maternal age-dependent mechanism involving reduced recombination
Department of Genetics and Molecular Medicine, Emory University School of Medicine 1462 Clifton Road, Atlanta, GA 30322 1Danish Centre for Human Genome Research, J.F.Kennedy Institute Glostrup, Denmark 2Department of Genetics an The Center for Human Genetics, Case Western Reserve University School of Medicine Cleveland, OH 44106, USA
*To whom correspondence should be addressed
Received April 17, 1994; Revised June 24, 1994; Accepted June 24, 1994
Over 300 cases of trisomy 21 were analyzed to characterize the causes of maternal non-disjunction and to evaluate the basis for maternal age-dependent trisomy 21. We confirmed the observation that recombination along 21q is reduced among non-disjoined chromosomes 21 and further demonstrated that the alterations in recombination are restricted to meiosis I origin. Analysis of the crossover distribution Indicates that reduction In recombination is not due simply to failure of pairing and/or absence of recombination In a proportion of cases. Instead, we observed an increase in both zero- and one-exchange events among trisomy 21-generating meloses suggesting that an overall reduction In recombination may be the underlying cause of non-disjunction. Lastly, we observed an age-related reduction In recombination among the melosis I cases, with older women having less recombination along 21q than younger women. Thus, reduced genetic recombination may be responsible, at least in part, for the association between advancing maternal age and trisomy 21.
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