Replication asynchrony increases in women at risk for aneuploid offspring.
We attempted to demonstrate a relation between a loss of replication control, centromere dysfunction, and predisposition to non-disjunction. Couples with a Down syndrome offspring were the high-risk probands. One-color FISH (fluorescent in-situ hybridization) was applied to interphase nuclei (lymphocytes). Replication pattern of two pairs of alleles, RB-1 and 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 timing 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 offspring. These findings may reflect a predisposition for meiotic non-disjunction in these women.
Amiel
A
A
Genetic Institute, Meir Hospital, Kfar-Saba, Israel.
Reish
O
O
Gaber
E
E
Kedar
I
I
Diukman
R
R
Fejgin
M
M
D000328:Adult; D000483:Alleles; D000782:Aneuploidy; D002503:Centromere; D002887:Chromosomes, Human, Pair 18; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D004261:DNA Replication; D004314:Down Syndrome / Q000235:genetics*; D005220:Fathers; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009035:Mothers; D009630:Nondisjunction, Genetic; D012307:Risk Factors