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

Abstract

Human trisomy is attributable to many different mechanisms and the relative importance of each mechanism is highly chromosome specific. The association between altered recombination and maternal non-disjunction is well documented: reductions in recombination have been reported for maternal meiosis I (MI) errors involving chromosomes 15, 16, 18 and 21 and increased recombination has been reported for meiosis II (MII) errors involving chromosome 21. We therefore investigated maternal X chromosome non-disjunction, to determine 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 females 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 further 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%) had no detectable transitions and so absent recombination is an important factor for X chromosome non-disjunction. However, similar to trisomy 15 and unlike trisomy 21, we observed a significant increase in the mean maternal age of transitional MI errors compared with nullitransitional cases. In our studies of MII errors, recombination appeared normal and there was no obvious effect of maternal age, distinguishing our results from MII non-disjunction of chromosomes 18 or 21. Thus, surprisingly, the risk factors associated with both MI and MII non-disjunction appear to be different for virtually every chromosome that has been adequately studied.

Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction

“…Interestingly, similar trend is also evident for chromosome 15, 18 and X chromosome (Robinson et al 1998;Thomas et al 2001;Bugge et al1998). This finding suggests two important possibilities.…”

An Opportune Life: 50 Years in Human Cytogenetics

“…In the XXYs of paternal origin, there is again no effect of parental age, with the majority resulting from failure of recombination in the pairing region of the X and Y chromosomes followed by nondisjunction at the first meiotic division (49). In contrast, the XXYs of maternal origin are associated with advanced maternal age and a variety of unusual patterns of recombination in the first or second meiotic division (51). The great majority of XXX females, whether ascertained as spontaneous abortions or live births, are the result of nondisjunction of the maternal X chromosome, usually occurring at the first meiotic division.…”

“…The great majority of XXX females, whether ascertained as spontaneous abortions or live births, are the result of nondisjunction of the maternal X chromosome, usually occurring at the first meiotic division. This is also associated with a marked increase in maternal age (51). XYY males are not found in excess among spontaneous fetal deaths, are not associated with an increase in paternal age, and are the result of fertilization of a 23,X oocyte by a sperm with an additional Y chromosome.…”

Klinefelter syndrome: Expanding the phenotype and identifying new research directions

“…4 Failure to recombine is also important in the genesis of 47,X M X M Y cases. Thomas et al 5 estimated that approximately 25% of these cases involve maternal meioses in which the two X chromosomes fail to pair and/or recombine with each other. However, Thomas et al 5 also observed another, curiously, abnormality of recombination in maternally derived cases.…”

“…Thomas et al 5 estimated that approximately 25% of these cases involve maternal meioses in which the two X chromosomes fail to pair and/or recombine with each other. However, Thomas et al 5 also observed another, curiously, abnormality of recombination in maternally derived cases. A small proportion of cases appeared to recombine at, or extremely close to, the centromere-normally a "dead" spot for recombination.…”