This proposal is designed to refine the understanding of gene linkage relationships in the mouse and allow precise comparative mapping analyses with the human genome. DNA obtained from a large series of [(C3H/HeJ-gld/gld x Mus spretus) F1 X C3H/HeJ-gld/gld] interspecific backcross mice will be used to identify genetic markers at interval of between 10 to 20 centi-Morgans throughout the genome. As this segregation map develops it will be utilized to identify and define the extent and border of conserved linkage groups common to mice and humans. Detailed analysis of mouse chromosome 1 genetics is the central focus of the proposal. The goals include: i) creation of a distal mouse chromosome 1 specific library; ii) detailed comparative mapping with syntenic groups on human chromosomes 1q, 2q and possibly 18q; iii) physical mapping studies to generate a molecular map of distal mouse chromosome 1 to complement the detailed genetic map and iv) comparative physical mapping of different Mus species and areas of the human genome. The large number of interspecific backcross mice (over 1200 available) combined with the generation of large numbers of markers will allow the resolution of a 0.5 cm genetic map of distal mouse chromosome 1. The refinement of the mouse genomic map at both a genetic and physical level will allow better analyses of the relationships between mouse genetic models for disease and their possible human counterparts as well as fundamental structure/function correlations concerning genomic organization. The studies should provide important insight into aspects of mammalian meiotic recombination and the evolution of mammalian genomes.
