Work in this lab and elsewhere over the past few years has led to a detailed genetic map of mouse chromosome 12 that incorporates many molecular probes. The experiments proposed here will build on this map both to address basic questions concerning the relationship between the genetic and physical organization of mammalian chromosomes and to develop chromosome 12 further as a model for the very high resolution analysis of chromosomes and chromosome regions in mammals including humans. Four groups of experiments are proposed. 1. Additional backcross experiments will be performed to refine the map of chromosome 12, concentrating on the extreme proximal and distal regions of the chromosome (cen-D12Nyu2 and Igh-Ca-ter, respectively) and on the region centered on the Fos proto-oncogene. 2. Two translocations (T(2;12)47Dn and T(5;12)31H) and an inversion (T25Rk) will be mapped genetically: their endpoints will be precisely localized; and the quantitate effects of the rearrangements on the distribution of recombination events over the chromosomes will be examined. The map of the chromosome in an interspecies (spretus x lab strain) backcross will be determined. The iv (situs inversus) mutation will be localized with respect to the distal endpoint of the T25Rk inversion. 3. Three regions of the chromosome that are densely marked genetically, centered on D12Nyu2, Fos, and Igh will be physically mapped using pulsed- field gel electrophoresis. 4. Using the 5 12 chromosome from the T31H translocation as starting material, the distal region of chromosome 12 will be cloned and restriction mapped.
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