The incidence, origin, and etiology of aneuploidy.

Aneuploidy, the presence of an extra or missing chromosome, is the most frequent cause of mental retardation and pregnancy loss in our species. Studies can be divided into those of incidence, origin, and etiology. Trisomy 21 is the most common aneuploidy among liveborns whereas monosomy X and trisomy 16 are the most frequent causes of pregnancy loss. Aneuploidy primarily arises by the process of nondisjunction in the first meiotic division of maternal meiosis; however, this varies among chromosomes in that some show a significant proportion of paternal and/or meiosis II errors. The most common etiological factor associated with aneuploidy is advancing maternal age and it is generally agreed that this is a result of the increasing likelihood of nondisjunction in the aging ovary. There has been intense debate as to the existence of of a paternal age effect and recent studies on human sperm suggest that there may be a small effect for the sex chromosomes. Furthermore, recent molecular studies on trisomic conceptuses have revealed a second etiological factor associated with nondisjunction, namely, reduced genetic recombination.