PHYSICAL AND COMPARATIVE MAPPING OF DISTAL MOUSE-CHROMOSOME-16

Distal mouse Chromosome 16 (Chr, 16) includes a region of conserved li nkage with human Chromosome 21 (Chr. 21). Mouse models of Down syndrom e based on trisomy Of distal Chr. 16 have several phenotypes similar t o those seen in human patients and have proven useful for correlating dosage imbalance of specific genes with specific developmental anomali es. The degree to which such findings can be related to Down syndrome depends on how well the conserved synteny is maintained. Twenty-four g enes have been mapped in both species and there are no discordancies, but the region could carry hundreds of genes. Comparative sequence rep resents the ultimate comparative map and will aid in identification of genes and their regulatory sequences. A physical map of the distal 4. 5 Mb of Chr. 16 has been assembled as all essential step toward a map of sequence-ready templates. The map consists of Si YACs and 15 BACs a nd includes 18 transcripts, 9 of which are mapped For the first time i n mouse, and 3 of which are, for the first time, described in either s pecies. YAC fragmentation was used to precisely localize the 49 marker s on the map. Comparison of this physical map with that of the corresp onding region on Chr. 21 shows conservation not only of gene order but of size in the 3 Mb from Cbr1 to Ets2; distal to Ets2, the human map is expanded.