Nondisjunction in trisomy 21: Origin and mechanisms

Chromosomal aneuploidy is a fundamental characteristic of the human species . In this review we summarize the knowledge about the origin and mechanisms of nondisjunction in human trisomy 21 that has accumulated during the last decade by using DNA polymorphism analysis. The first molecular correlate o f nondisjunction in humans is altered recombination, meiosis I errors being associated with reduced recombination and maternal meiosis II errors with increased recombination between the nondisjoined chromosomes. Thus, virtual ly all maternal meiotic errors of chromosome 21 seem to be initiated in mei osis I. Advanced maternal age remains the only well documented risk factor for maternal meiotic nondisjunction! but there is, however, still a surpris ing lack of understanding of the basic mechanisms behind the maternal age e ffect. Copyright (C) 2001 S.Karger AG, Basel.