The molecular genetics of Down syndrome

Major advances have occurred in the understanding of the genetics of DS since the discovery a little more than 30 years ago that it resulted from an extra copy of HSA-21. It has been learned that only a small region of HSA-21 is required in triplicate to produce at least some of the DS phenotype. Future work will clarify which regions are responsible for particular phenotypes of interest. The mechanisms by which extra genetic material leads to phenotypic abnormalities in DS and other aneuploidies appear to be complex. Although gene dosage effects are operative for many loci, they do not appear to be strictly operative for all genes. A more thorough understanding of the effects of aneuploidy on gene expression is needed. To understand adequately the mechanisms by which extra genetic material leads to particular phenotypic features will require the use of animal models. The trisomy 16 mouse, as well as new transgenic and partial trisomic mouse lines currently being developed, may be of particular help in this endeavor.