Having presented a detailed review of both the theoretical and experimental aspects of our current understanding of aneuploidy, I now turn to a consideration of three important human clinical problems associated with aneuploidy. Two of these are specific disorders caused by chromosome imbalance: trisomy 21, with its phenotype of Down syndrome, and monosomy X (or XO), with its phenotype of Turner syndrome or gonadal dysgenesis. The third problem is not a single genetic disorder, but, rather, a whole group of acquired disorders in which aneuploidy appears to play a significant but poorly understood role – cancer. For the first two conditions, the intent, once again, is to focus on questions of mechanism and to relate what is known about the chromosomes involved to the phenotypes that are observed. If it is not possible to make such connections, the discussion will point up those issues which appear to offer the most with regard to arriving at mechanistic solutions.

The discussion of trisomy 21 in this chapter will begin with what is known about the genetic structure of human chromosome 21. It will proceed to consideration of first the implications of the imbalance of loci known to be on the chromosome and then of those aspects of Down syndrome the relation of which to imbalance of loci on chromosome 21 is not presently apparent. Finally, a newly developed animal model system for trisomy 21 will be discussed.