COMPARATIVE MAPPING OF THE HUMAN 22Q11 CHROMOSOMAL REGION AND THE ORTHOLOGOUS REGION IN MICE REVEALS COMPLEX CHANGES IN GENE ORGANIZATION

The region of human chromosome 22q11 is prone to rearrangements. The r esulting chromosomal abnormalities are involved in Velo-cardio-facial and DiGeorge syndromes (VCFS and DGS) (deletions), ''cat eye'' syndrom e (duplications), and certain types of tumors (translocations), As a p relude to the development of mouse models for VCFS/DGS by generating t argeted deletions in the mouse genome, we examined the organization of genes from human chromosome 22q11 in the mouse, Using genetic linkage analysis and detailed physical mapping, we show that genes from a rel atively small region of human 22q11 are distributed on three mouse chr omosomes (MMU6, MMU10, and MMU16), Furthermore, although the region co rresponding to about 2.5 megabases of the VCFS/DGS critical region is located on mouse chromosome 16, the relative organization of the regio n is quite different from that in humans, Our results show that the in stability of the 22q11 region is not restricted to humans but may have been present throughout evolution, The results also underscore the im portance of detailed comparative mapping of genes in mice and humans a s a prerequisite for the development of mouse models of human diseases involving chromosomal rearrangements.