We have been analyzing somatic cell hybrids and inter(sub)species crosses to develop a multilocus genetic map of the mouse largely comprised of expressed genes and pseudogenes. Most genes are mapped by the analysis of the progeny of two sets of genetic crosses, an interspecies backcross and an intersubspecies backcross. DNAs from these mice have been typed for over 750 loci about half of which have been previously positioned to permit mapping of newly defined genes to specific positions on the linkage map. These studies have resulted in the genetic mapping of several hundred new genes including, most recently, brain cDNAs, genes encoding bone morphogenetic proteins, opioid receptor proteins, tyrosine kinases, and sulfotransferases. Specific map locations can be useful information since proximity to a known developmental mutation can identify such a gene as a potential candidate for the abnormal phenotype. Thus, a gene for a new cartilage-derived morphogenetic factor was mapped to a site on Chromosome 2 near the mutation bp (brachypodism). Subsequent analysis demonstrated that the mutation was due to a specific abnormality of this locus. Other studies have focussed on the organization of multigene families in the mammalian genome and on the comparative linkage relationships of homologous genes in man and mouse.
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