GENETIC MAPPING OF MOUSE CHROMOSOMAL GENES

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Abstract

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 new homeobox genes, immune system genes, peroxiredoxin genes and genes involved in tooth development. We have also recently begun 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. Specific map locations can be useful for several reasons. In particular, proximity to a known developmental mutation can identify the gene as a potential candidate for the abnormal phenotype. This year we used subtractive hybridization to identify candidate genes for the regulation of interferon production. Subtractive hybridization using mice that differ at If1 was used to clone a series of genes differentially expressed in these mice. Genes were mapped to multiple sites in the mouse genome including one novel gene which was mapped to distal chromosome 3 and thus represents a candidate for If1.