A complicated genetic insult

The finished sequence of chromosome 21 contains all of the possible genes that contribute primarily to anomalous development in Down's syndrome. Predictions about the contributions of individual genes to the disease phenotypes can be tested in animals. Comparative mapping in the mouse has identified candidate orthologs for about 150 human chromosome 21 genes. These genes map to the same relative positions in three highly conserved segments on mouse chromosomes 16, 17, and 10. Transgenic mice have extra copies of one or several genes, and segmental trisomy or inclusion of a human chromosome 21 in a mouse produces dosage imbalance for hundreds of the same genes that contribute to Down's syndrome.