Naturally occurring inherited retinal degeneration has been recognized in humans, cats and dogs. Retinitis pigmentosa (RP) is a heterogeneous group of heritable retinopathies causing blindness in humans. Progressive retinal atrophy (PRA) is the counterpart term in veterinary medicine. A complete and early-onset retinal degeneration with autosomal recessive inheritance has been described in Persian cats. Previous funding has supported the characterization of the inheritance, as well as clinical and histological features of this disease, and has genetically mapped the PRA-causing locus in cats to a specific chromosomal region. The backcross cat pedigree has been extended to 61 individuals for genetic mapping and disease characterization.
Ophthalmic and neuro-ophthalmic examinations are performed on each animal on multiple occasions to determine disease status. A full genome-wide scan was performed on the backcross Persian PRA pedigree representing five generations.
Feline-specific microsatellite markers were selected from feline linkage/RH maps with an average spacing of 10cM. Two-point linkage analysis was performed using the program LINKAGE. For fine mapping, additional markers within or flanking the critical regions were analyzed. This data suggested a critical region responsible for PRA is located at the short arm of a feline chromosome. However, poor coverage of the feline map prevents adequate comparison between humans, cats, and dogs in this region and does not clearly suggest a candidate gene. One hundred seventy-nine additional markers have been genotyped in the region, none of which have increased the likelihood of the gene identification. Thus, the overall genetic map of the region may be incorrect or since the significance values for the association are not increasing, a false region may have been identified and a further genome analysis needs to be performed. This project will continue to scan the proposed critical region to identify candidate gene mutation(s) within the region and also increase the marker coverage at other parts of the genome.