A goal of our research is to characterize genetic organization in the domestic cat and to develop genomic resources facilitating and establishing Felis catus as a useful animal model contributing to our understanding of human hereditary disease analogues, neoplasia, genetic factors associated with host response to infectious disease and mammalian genome evolution. In order to map and characterize genes associated with inherited pathologies in the domestic cat which mirror inherited human conditions we have recently completed a second generation linkage map of integrated microsatellite (Type II) and Type I (coding genes) in the domestic cat. The map was generated in a 134-member, multi-generation backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis) and consists of 334 markers including 81 Type I loci and 253 Type II loci (246 autosomal and 7 X-linked microsatellites. The average intragroup inter-marker distance of 11 centimorgans (cM) was observed over the 18 feline autosomes and the X chromosome. In order to increase marker density for greater genetic linking mapping resolution in disease pedigrees, we have isolated an additional 700 dinucleotide repeat loci from a (dCA.dGT) enriched library. Primers for amplification have been designed and tested for both product performance and locus heterozygosity in a panel of outbred domestic cats. The loci are currently being genotyped in a cat x rodent radiation hybrid panel, recently used in construction of a Type I/Type II radiation hybrid map (see ZO1 BC 10265-05 LGD). A highly efficient approach is being utilized with amplifications performed in 384-well format and traditional gel-based assays have been replaced by a homogeneous 5'-nuclease assay involving a single common probe for all genetic markers. Following genotyping, the markers will be integrated with the current radiation hybrid map of the cat, including 421 Type I and 265 Type II markers. Microsatellites mapped at regular physical intervals will be genotyped and mapped in a large multi-generation domestic cat pedigree to generate a genetic linkage map with full genome coverage of Felis catus and of sufficient resolution for linkage mapping in disease pedigrees.
