Non-disjunction of chromosome 13

Abstract

We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter finding is unique among human autosomal trisomies, where maternal MI (trisomies 15, 16, 21, 22) or MII (trisomy 18) errors dominate. Of the nine paternally derived cases five were of MII origin but none arose from MI errors. There was some evidence for elevated maternal age in cases with maternal meiotic origin for liveborn infants. Maternal and paternal ages were elevated in cases with paternal meiotic origin. This is in contrast to results from a similar study of non-disjunction of trisomy 21 where paternal but not maternal age was elevated. We find clear evidence for reduced recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms that determine non-disjunction of human chromosomes, consistent with the diversity of findings for other trisomies.

Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew

“…In studies of trisomy 22 Hall et al [7] reported a preponderance of maternally-derived cases, typically arising from MI nondisjunction and frequently involving failure of recombination between the homologs. The results were similar for trisomy 13, although with a higher proportion of cases of maternal MII origin [8,9]. Hall et al [7] compared their observations on trisomy 22 with trisomies involving other acrocentric chromosomes and with non-acrocentric trisomies and concluded that there are at least three different nondisjunctional patterns: those that apply to all chromosomes, those that apply to groups of chromosomes (e.g., trisomies involving acrocentric chromosomes, since maternal MI errors and recombination failure are features of these), and those that are chromosome-specific (e.g., trisomy 16, since it is almost always due to maternal MI errors but – unlike other trisomies – has no apparent contribution of recombination failure).…”

Is There a Paternal Age Effect for Aneuploidy?

“…Nicolaidis and Petersen [1998] reviewed the parental origin in a total of 42 cases from 2 molecular studies [Zaragoza et al, 1994;Robinson et al, 1996] showing 88% maternal and 12% paternal errors. A recent study by Bugge et al [2007] reported some evidence for paternal-age-related effects for trisomy 13. That is, they found a greater paternal age in trisomy 13 cases with paternal meiotic origin compared to controls.…”

Meiotic Recombination in Human Oocytes

“…Studies conducted over the past 10–20 years have identified the first molecular correlate of these abnormalities, as disturbances in meiotic recombination have been linked to a variety of human trisomies of maternal origin [1]. Specifically, reductions in recombination have been associated with nondisjunction of chromosomes 13, 15, 16, 18, 21, 22 and the sex chromosomes [2],[3],[4],[5],[6],[7],[8],[9],[10], and alterations in the location of crossover events with trisomies 16 and 21 and sex chromosome trisomies [5],[8],[10]. These associations are consistent with similar observations in model organisms such as Drosophila [11] and S. cerevisiae [12], but the magnitude of the effect in humans has been surprising.…”