Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy(ascertained through Prader-Willi syndrome) and 13 cases of trisomy ofmaternal origin were densely typed for microsatellite loci spanningchromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19meiosis II (MII) errors and 12 mitotic errors were identified. The geneticlength of a map created from the MI errors was 101 cM, as compared with amaternal length of 137 cM based on CEPH controls. No significantdifferences were detected in the distribution of recombination events alongthe chromosome arm and a reduction was seen for most of the chromosome 15intervals examined. It was estimated that 21% of tetrads leading to MInon-disjunction were achiasmate, which may account for most or all of thereduction in recombination noted. The mean age of mothers of casesinvolving MI errors which showed no transitions from heterodisomy toisodisomy was significantly lower (32.7) than cases showing one or moreobservable transitions (36.3) (P < 0.003, t -test). However, even amongchiasmate pairs the highest mean maternal age was seen for multipleexchange tetrads. Chromosome- specific differences in maternal age effectsmay be related to the normal distribution of exchanges (and theirindividual susceptibilities) for each chromosome. However, they may alsoreflect the presence of multiple factors which act to ensure normalsegregation, each affected by maternal age in a different way and varyingin importance for each chromosome.