Susceptible chiasmate configurations of chromosome 21 predispose to non–disjunction in both maternal meiosis I and meiosis II

Abstract

The cause of non-disjunction of chromosome 21 remains largely unknown. Advanced maternal age is associated with both maternal meiosis I (MI) and meiosis II (MII) non-disjunction events. While reduced genetic recombination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with maternal MII errors to test the hypothesis that segregation at MII may also be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recombination that is largely restricted to proximal 21q. Thus, while absence of a proximal recombination appears to predispose to non-disjunction in MI, the presence of a proximal exchange predisposes to non-disjunction in MII. These findings profoundly affect our understanding of trisomy 21 as they suggest that virtually all maternal non-disjunction results from events occurring in meiosis I.

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).…”

“…Proteins actively functioning in these processes are essential for proper development, but their specific roles in oocyte maturation are difficult to unravel. The "two hit" model proposed in 1996 (25) and extended recently (41) offer an alternative explanation to non-disjunction cases involving recombination. Susceptible recombinants generate a first hit, and then a second hit, related to mother age, triggers non-disjunction events.…”

A fascination with chromosome rescue in uniparental disomy: Mendelian recessive outlaws and imprinting copyrights infringements

“…The implications for UPD16 may be straightforward: the noted frequency of trisomy 16, its unique and constant maternal origin, and the reduced recombination going along with me1-generated disomies 64 should explain the relatively high frequency of UPD16 mat void of isodisomy (reviewed by 20 A somewhat similar commentary could hold true for the UPD's 21 derived from a trisomy 21 where the trend seems as follows: the risk of isodisomy is lowered and the chance of heterodisomy maintained if a lack or a dearth of crossing over recombination is a cause for me1 nondisjunction, as is indeed the case 66 ; such a risk is lessened as well if a (proximal) increase in recombination at me1 favours me2 nondisjunction, which has also been well documented. 67 We see therefore that the mood of chromosome 21, in pathology, is against isodisomic deviancy and does not at all favour the works of 'recessive outlaws'! In addition, UPD21 is clinically innocuous at the difference of UPD16 mat (reviewed by Engel and Antonarakis 6 ) and the pair presents a relatively small number of genes up for recessive Chromosome rescue in uniparental disomy E Engel mutations.…”

Trisomie 21 : 50 ans entre médecine et science

“…Un échange unique en position télomérique était associé à une erreur de première division méiotique tandis qu'un échange unique en position centromérique était associé à une erreur de deuxième division méiotique [7]. En effet, il est possible qu'un échange péricentromérique produise un enchevêtrement chromosomique entraînant une non-disjonction de première division méiotique de l'ensemble du bivalent.…”