Non-disjunction of chromosome 18

Abstract

A sample of 100 trisomy 18 conceptuses analysed separately and together with a published sample of 61 conceptuses confirms that an error in maternal meiosis II (MII) is the most frequent cause of non-disjunction for chromosome 18. This is unlike all other human trisomies that have been studied, which show a higher frequency in maternal meiosis I (MI). Maternal MI trisomy 18 shows a low frequency of recombination in proximal p and medial q, but not the reduction in proximal q observed in chromosome 21 MI non-disjunction. Maternal MII non-disjunction does not fit the entanglement model that predicts increased recombination, especially near the centromere. Whereas recent data on MII trisomy 21 show the predicted increase in recombination proximally, maternal MII trisomy 18 has non-significantly reduced recombination. Therefore, chromosome-specific factors must complicate the simple model of susceptible chiasma distributions interacting with age-dependent deterioration of the meiotic mechanism. For chromosome 18, 30% of tetrads are nullichiasmate in maternal MI non-disjunction, but nullichiasmates are not observed in maternal MII non-disjunction. Chiasma distributions from normal chromosome 18 meioses provide no evidence for normal disjunction from nullichiasmate tetrads. We extend this study to examine the remaining autosomes and find no evidence for normal disjunction from nullichiasmate tetrads generally.

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

“…However, it is not clear whether the same proportion of nonrecombinants applies to all other chromosomes. Certainly, there are reports that lack of recombination on chromosome 18 is a rare event, 10 and, therefore, the percentage of UPD cases not identified by CMA in this study may not be generalizable to other chromosomes. Further study is necessary to determine the percentage of UPD cases for other chromosomes that may also be missed by CMA, particularly for those chromosomes susceptible to UPD disorders.…”

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

“…As with chromosome 18 (Bugge et al 1998), segregation of chromosome 21 univalents is always associated with MI-type errors (Lamb et al 1996;Oliver et al 2008). Similarly, bivalents with a single distal chiasma are associated with MI-type trisomy 21 (Lamb et al 1996;Oliver et al 2008) and 16 (Nagaoka et al 2012).…”

An Opportune Life: 50 Years in Human Cytogenetics

“…About 90% of most other trisomies are of maternal origin, with the majority resulting from an error at the first meiotic division and only a minority resulting from an error at the second (17). The only clear exception to this is trisomy 18, where the vast majority, if not all, are the result of an error of maternal meiosis, and in the great majority of these the error occurs at the second meiotic division (2). Irrespective of the precise mechanism of the nondisjunction event leading to the trisomic conceptus, all are associated with increased maternal age, although there are significant differences among different chromosomes.…”