SUSCEPTIBLE CHIASMATE CONFIGURATIONS OF CHROMOSOME-21 PREDISPOSE TO NONDISJUNCTION IN BOTH MATERNAL MEIOSIS-I AND MEIOSIS-II

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 re combination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with ma ternal MII errors to test the hypothesis that segregation at MII may a lso be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recomb ination that is largely restricted to proximal 21q. Thus, while absenc e of a proximal recombination appears to predispose to nondisjunction in MI, the presence of a proximal exchange predisposes to non-disjunct ion in MII. These findings profoundly affect our understanding of tris omy 21 as they suggest that virtually all maternal non-disjunction res ults from events occurring in meioisis I.