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

Abstract

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome-specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome.

Uniparental disomy: can SNP array data be used for diagnosis?

“…One study demonstrated that up to 21% of cases of maternal UPD15 show no evidence of recombination during meiosis I. 3 In our laboratory, a total of 14 cases of UPD15 were ascertained from 1998 to 2011, 11 of which were included in this study. The three cases not analyzed by CMA each showed homozygosity for at least three maternal markers; given the concordance of microsatellite markers and CMA results for all analyzed cases, we assume these three cases would be detected by CMA.…”

“…176270). 2 Two well-known factors that predispose to nondisjunction are maternal age 3 and aberrant recombination 4 (e.g., lack of recombination or recombination too close to the centromere or telomere).…”

A fascination with chromosome rescue in uniparental disomy: Mendelian recessive outlaws and imprinting copyrights infringements

“…Threequarters of them result from maternal me1 nonsegregation events and, as for chromosome 21, are aided by a lack or a dearth of recombination. Close to 10% are of mitotic origin, 69 so that roughly one-third, or 3% of all 15 trisomies may contribute to maternal or paternal isodisomy with the implied risk of a recessive trait from a mutant. Given the high contribution of maternal meiotic nondisjunction to trisomy 15, most detected rescues will have to represent cases of maternal UPD.…”

Circulating adiponectin levels, body composition and obesity-related variables in Prader–Willi syndrome: comparison with obese subjects

“…[1][2][3] Approximately 70% of PWS cases are due to a paternal deletion on chromosome 15 (15q11-q13 region), 25% of PWS cases have maternal uniparental disomy (UPD) of chromosome 15 and the remaining cases result from genetic imprinting defects. [4][5][6][7][8] Much interest now revolves around the role of adipose tissue as an endocrine organ, capable of producing hormones and cytokines such as tumor necrosis factor-a, plasminogen activating inhibitor-1, leptin, interleukin-6, resistin and, more recently, adiponectin. [9][10][11][12] Adiponectin is abundant in the circulation of nondiabetic humans, but is decreased in patients with obesity, type 2 diabetes and cardiovascular disease and higher in women than in men.…”