Maternal sex chromosome non-disjunction: evidence for X chromosome-specific risk factors

Human trisomy is attributable to many different mechanisms and the relative importance of each mechanism is highly chromosome specific. The associatio n between altered recombination and maternal non-disjunction is well docume nted: reductions in recombination have been reported for maternal meiosis I (MI) errors involving chromosomes 15, 16, 18 and 21 and increased recombin ation has been reported for meiosis II (MII) errors involving chromosome 21 , We therefore investigated maternal X chromosome non-disjunction, to deter mine whether the effects of recombination are unique to the X chromosome or similar to any of the autosomes thus far studied. We genotyped 45 47,XXX f emales and 95 47,XXY males of maternal origin. Our results demonstrate that 49% arose during MI, 29% during MII and 16% were postzygotic events; a fur ther 7% were meiotic but could not be assigned as either MI or MII because of recombination at the centromere, Among the MI cases, a majority (56%) ha d no detectable transitions and so absent recombination is an important fac tor for X chromosome nondisjunction. However, similar to trisomy 15 and unl ike trisomy 21, we observed a significant increase in the mean maternal age of transitional MI errors compared with nullitransitional cases. In our st udies of MII errors, recombination appeared normal and there was no obvious effect of maternal age, distinguishing our results from MII non-disjunctio n of chromosomes 18 or 21, Thus, surprisingly, the risk factors associated with both MI and MII non-disjunction appear to be different for virtually e very chromosome that has been adequately studied.