Origin and mechanisms of non-disjunction in human autosomal trisomies

Chromosomal aneuploidy is one of the major causes of pregnancy wastage. In this review we summarize the knowledge about the origin and mechanisms of non-disjunction in human autosomal trisomies 8, 13, 15, 16, 18, and 21, accumulated during the last decade by using DNA polymorphism analysis. Maternal meiosis I non-disjunction is the most important single class, but chromosome-specific patterns exist. For the acrocentric chromosomes 15 and 21, meiosis I errors predominate among the maternal errors, in contrast to trisomy 18 where meiosis II errors predominate. For trisomy 16, virtually all cases are due to maternal meiosis I non-disjunction. Postzygotic (mitotic) non-disjunction constitutes 5-15% of cases of trisomies 15, 18, and 21, whereas for trisomy 8 and trisomy 8 mosaicism the majority of cases are due to mitotic non-disjunction. For paternal non-disjunction of chromosomes 18 and 21, meiosis II or mitotic errors predominate. There is aberrant meiotic recombination associated with maternal meiotic non-disjunction in all trisomies studied in detail so far. Advanced maternal age remains the only well documented risk factor for maternal meiotic non-disjunction, but there is, however, still a surprising lack of understanding of the basic mechanism(s) behind the maternal age effect.