Human aneuploidy: lessons from achiasmate segregation in Drosophila melanogaster

Aneuploidy is a crucial issue in human reproductive biology, accounting for both a significant proportion of miscarriages and, among liveborns, multip le congenital malformation syndromes such as Down Syndrome. Although the et iology of human aneuploidy remains poorly understood, recent studies have e lucidated certain fundamental correlates of meiotic nondisjunction, such as altered recombination. These features are extraordinarily similar to those associated with chromosome misbehavior in Drosophila melanogaster females. Furthermore, these organisms also share a significant level of achiasmate chromosome nondisjunction. Here we describe in detail the processes of achi asmate chromosome segregation in Drosophila and discuss how they may be mos t effectively applied to our understanding of the etiology of human aneuplo idy. In particular, we examine the possibility that similar "backup" mechan isms of chromosome segregation might function in mammalian meiosis, particu larly mammalian females. Drawing upon observations made in flies, we also p ropose a new model for the segregation of achiasmate chromosomes in humans.