Replication asynchrony increases in women at risk for aneuploid offspring

We attempted to demonstrate a relation between a loss of replication contro l, centromere dysfunction, and predisposition to non-disjunction. Couples w ith a Down syndrome offspring were the high-risk probands. One-color FISH (fluorescent in-situ hybridization) was applied to interphas e nuclei (lymphocytes). Replication pattern of two pairs of alleles, RB-1 a nd 21q22, were studied, and the rate of aneuploidy was estimated using two alpha-satellite probes of chromosomes 8 and 18. Our results suggest the existence of an association between replication tim ing and the rate of non-disjunction. A higher rate of allele asynchrony and aneuploidy was found in older women and in mothers of a Down syndrome offs pring. These findings may reflect a predisposition for meiotic non-disjunct ion in these women.