Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21

Abstract

Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non-disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.

Origen parental, estado de no disyunción y recombinación meiótica del cromosoma 21 extra en el síndrome de Down: estudio en una muestra de población colombiana

“…The above data suggest two clusters ( Figure 3, dashed ovals), the first is the MI-No recombination-distal recombination cluster and the second is the MII-Proximal recombination-medial recombination cluster. Presence of these clusters support the hypoth-esis that almost all non-disjunction cases are the result of errors initiated at MI (19,25).…”

“…The associations between (a) specific meiotic errors and (b) absence of or localized recombination suggested that all non-disjunction events are initiated during MI and then resolved at either MI or MII (19).…”

A High-Resolution Physical Map of Human Chromosome 21p Using Yeast Artificial Chromosomes

“…The remaining 5% of DS patients have a trisomy of chromosome 21 as a result of a Robertsonian translocation, mostly involving one of the other acrocentric chromosomes (Antonarakis 1993). The parental origin of the extra copy can be determined accurately using highly informative chromosome 21-specific polymorphic markers (Lamb et al 1997). However, because no chromosome 21p or centromere-specific polymorphic markers are available, the study of the meiotic nondisjunction is based on data obtained from chromosome 21q markers only (Antonarakis et al 1992).…”

Trisomie 21 : 50 ans entre médecine et science

“…Dans 2 % des cas, il existe une non-disjonction mitotique postzygotique [3]. Ensuite, la fréquence et le mécanisme de non-disjonction varient en fonction du contexte gamétique puisque, dans l'ovocyte, une erreur de la première division méiotique (MI) [52] est trois fois plus fréquente qu'une erreur de deuxième division méiotique (MII) tandis qu'elles sont de fréquence égale dans les spermatocytes [4,5]. …”