Evolutionary breakpoints on human chromosome 21

Segments of the long arm of human chromosome 21 are conserved, centromere t o telomere, in mouse chromosomes 16, 17, and 10. There have been 28 genes i dentified in human chromosome 21 between TMPRSS2, whose orthologue is the m ost distal gene mapped to! mouse chromosome 16, and PDXK, whose orthologue is the most proximal gene mapped to! mouse chromosome 10. Only 6 of these 2 8 genes have been mapped in mouse, and all are located on chromosome 17. To better define the chromosome 17 segment and the 16 to 17 transition, we us ed a combination of mouse radiation hybrid panel mapping and physical mappi ng by mouse:human genomic sequence comparison. We have determined the mouse chromosomal location of an additional 12 genes, predicted the location of 7 more, and defined the endpoints of the mouse chromosome 17 region. The mo use chromosome 16/chromosome 17 evolutionary breakpoint is between human ge nes ZNF295 and UMODL1, showing there are seven genes in the chromosome 16 s egment distal to Tmprss2. The chromosome 17/chromosome 10 breakpoint seems to have involved a duplication of the gene PDXK, which on chromosome 21 lie s immediately distal to the KIAA0179 gene. These data suggest that there ma y be as few as 21 functional genes in the mouse chromosome 17 segment. This information is important for defining existing and constructing more compl ete mouse models of Down syndrome.