SEPARATION ANXIETY - THE ETIOLOGY OF NONDISJUNCTION IN FLIES AND PEOPLE - COMMENTARY

Two new studies examine the recombinational history of human chromosom es that nondisjoin at the first meiotic division in females. Our analy sis of these studies suggests two possible etiologies of nondisjunctio n 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 displa y unusual patterns of exchange. The patterns of exchange and nondisjun ction observed for human chromosome 21 parallel those exhibited by a m utation in Drosophila that impairs spindle assembly and function. Base d on these similarities, we propose that nondisjunction of chromosome 21 in human females results from an age-dependent loss of spindle-form ing ability. The recombinational histories of nondisjoining human X ch romosomes are quite different from those of chromosome 21, but rather parallel those obtained for spontaneous nondisjunction in Drosophila f emales. The data for X chromosome disjunction in both species can be e xplained by a model in which nondisjunction is the consequence of the age-dependent movement of transposable elements. According to this mod el, nondisjunction is explained as the consequence of the repair of tr ansposon-induced breaks in the DNA. Both models provide reasonable alt ernatives to biologically implausible explanations such as the 'produc tion line hypothesis'.