Ongoing Characterization of a Feline Rod Cone Dysplasia

Abstract

Abstract: : Purpose:Naturally occurring, inherited retinal degeneration, termed progressive retinal atrophy (PRA), has been recognized in humans, dogs, rodents, and cats. A complete and early onset retinopathy with suggested autosomal recessive inheritance has been noted in Persian cats, but only the terminal stages of the disease (15 weeks of age) have been described. Characterization of this disease was initiated to develop a novel feline model for retinitis pigmentosa, group of heritable diseases causing blindness in humans. Our objective was to identify possible candidate genes and genetically map the PRA–causing genes on feline chromosomes. Methods:Ophthalmoscopic and histological examinations were performed in a longitudinal study to aid identification of similar diseases and likely candidate genes in other species. A pedigree of cats segregating for PRA was generated and genotyped with microsatellite markers to test genetic linkage with PRA. Twelve candidate genes for PRA were selected based on similar disease phenotypes (AIPL1, CRB1, CRX, GUCY2D, PDE6A, PDE6B, RDS, RGPRIP1, RHO, RP1, RPE65 and TULP1). Linkage mapping of chromosomal regions responsible for PRA was performed using feline microsatellite markers for 34 cats of 4 generations in the affected Persian cat pedigree. Thirty two microsatellite markers were selected from the feline hybrid panel. Two–point linkage analysis was performed using the LINKAGE program. Results:Photoreceptors degenerate rapidly resulting in complete blindness by 15 weeks of age. Twenty–seven kittens were added to our pedigree by backcross for disease characterization and linkage mapping. To date, 12 markers have been excluded at &#952 = 0.01 and 16 markers at &#952 = 0.1. FCA304, a microsatellite predicted to be in the same region as gene RHO showed an exclusion from PRA disease phenotype at &#952 = 0.13 with LOD score –2.05. FCA140 and F124, microsatellite markers spanning the inferred regions as GUCY2D and AILP1 based on chromosome conservation, were excluded from PRA at &#952 = 0.12 with LOD score –2.09. Conclusions:Our preliminary linkage data suggested that genes RHO, GUCY2D and AIPL1 can be excluded for this feline rod cone dysplasia.

Keywords: retinal degenerations: hereditary • linkage analysis • retina