Trisomy 21: association between reduced recombination and nondisjunction.

Abstract

To assess the association between recombination and nondisjunction of chromosome 21, we analyzed cytogenetic and DNA markers in 104 trisomy 21 individuals and their parents. Our DNA marker studies of parental origin were informative in 100 cases, with the overwhelming majority (94) being maternal in origin. This value is significantly higher than the 75%-80% maternal nondisjunction rate typically observed in cytogenetic studies of trisomy 21 and illustrates the increased accuracy of the molecular approach. Using the maternally derived cases and probing at 19 polymorphic sites on chromosome 21, we created a genetic map that spans most of the long arm of chromosome 21. The map was significantly shorter than the normal female linkage map, indicating that absence of pairing and/or recombination contributes to nondisjunction in a substantial proportion of cases of trisomy 21.