Separation anxiety: the etiology of nondisjunction in flies and people.

Abstract

Two new studies examine the recombinational history of human chromosomes that nondisjoin at the first meiotic division in females. Our analysis of these studies suggests two possible etiologies of nondisjunction in terms of well-understood properties of chromosome mechanics. For both the X chromosome and for chromosome 21, 60-70% of nondisjoined chromosomes are derived from chiasmate bivalents, many of which display unusual patterns of exchange. The patterns of exchange and nondisjunction observed for human chromosome 21 parallel those exhibited by a mutation in Drosophila that impairs spindle assembly and function. Based on these similarities, we propose that nondisjunction of chromosome 21 in human females results from an age-dependent loss of spindle-forming ability. The recombinational histories of nondisjoining human X chromosomes are quite different from those of chromosome 21, but rather parallel those obtained for spontaneous nondisjunction in Drosophila females. The data for X chromosome disjunction in both species can be explained by a model in which nondisjunction is the consequence of the age-dependent movement of transposable elements. According to this model, nondisjunction is explained as the consequence of the repair of transposon-induced breaks in the DNA. Both models provide reasonable alternatives to biologically implausible explanations such as the 'production line hypothesis'.