RECOMBINATION AND MATERNAL AGE-DEPENDENT NONDISJUNCTION - MOLECULAR STUDIES OF TRISOMY-16

Trisomy 16 is the most common human trisomy, occurring in greater than or equal to 1% of all clinically recognized pregnancies. It is though t to be completely dependent on maternal age and thus provides a usefu l model for studying the association of increasing maternal age and no ndisjunction. We have been conducting a study to determine the parent and meiotic stage of origin of trisomy 16 and the possible association of nondisjunction and aberrant recombination. In the present report, we summarize our observations on 62 spontaneous abortions with trisomy 16. All trisomies were maternally derived, and in virtually all the e rror occurred at meiosis I. In studies of genetic recombination, we ob served a highly significant reduction in recombination in the trisomy- generating meioses by comparison with normal female meioses. However, most cases of trisomy 16 had at least one detectable crossover between the nondisjoined chromosomes, indicating that it is reduced-and not a bsent-recombination that is the important predisposing factor. Additio nally, our data indicate an altered distribution of crossing-over in t risomy 16, as we rarely observed crossovers in the proximal long and s hort arms. Thus, it may be that, at least for trisomy 16, the associat ion between maternal age and trisomy is due to diminished recombinatio n, particularly in the proximal regions of the chromosome.