The mouse has been used as the model mammalian system for genome analysis. We have been engaged in the development of a high density genetic map of the mouse by analysis of several multilocus crosses derived from interspecies or intersubspecies matings. DNAs from these mice have been typed for over 1200 loci, about half of which have also been genetically mapped by other investigators. This permits us to map newly defined genes to specific positions in the genetic map, and to integrate our data into composite maps of each chromosome. Emphasis has been placed on mapping expressed genes to permit comparative analysis with the maps of other species and to contribute to efforts to identify genes involved in inherited developmental disorders. These studies have, most recently, resulted in the genetic mapping of genes encoding chemokine receptors, heat shock proteins, genes expressed in lens, thymic stroma, or connective tissue, immune system genes, and SH3 domain genes.Specific map locations can be useful for several reasons. First, such information contributes to the comparative analysis of homologous genes in man and mouse. For example, we examined the cluster of formylpeptide receptor genes in man and mouse. We found that the FPR gene cluster has undergone differential expansion in these species such that one expressed human gene has no counterpart in mouse, and 4 of the mouse genes (only two of which are pseudogenes) have no human counterparts. Second, proximity to a known developmental mutation can identify such a gene as a potential candidate for the abnormal phenotype. We recently mapped the gene encoding the lens protein gamma crystallin to proximal mouse chromosome 16 near a developmental mutation that results in lens opacity (cataracts). The lens protein gene is now being evaluated as a potential candidate for this mutation.We have recently begun using physical mapping techniques. We are using pulsed field gels to determine gene order and distance for genes not separable by recombination. We have most recently applied this approach to determine the proximity of Myc and a newly identified tumor specific integration site of mammary tumor virus. We are also using a radiation hybrid DNA panel to develop an integrated physical and genetic map of Chr 5. To date, we have added almost 50 loci to the RH map of this chromosome. - Mouse genome, mapping, comparative mapping
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