Molecular genetic investigations into inherited progressive retinal degenerations of dogs and cats

• Main Author: Gould, D. J.
• Published: University of Cambridge 1998
• Subjects: 591.35
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599550

Generalized Progressive Retinal Atrophy (gPRA) represents an inherited group of retinal degenerations affecting pedigree dogs and cats. The disease is genetically heterogeneous between breeds, and with the exception of rod-cone dysplasia 1 (<I>red1</I>) in the Irish setter, the genetic causes remain unknown. The disease closely resembles retinitis pigmentosa, the commonest cause of inherited blindness in man. I have used a candidate gene approach in an attempt to identify mutations causing gPRA in dogs and cats. Rom-1, a structural gene of the rod photoreceptor of the retina, was cloned, sequenced, and analyzed in the dog. Single Stranded Conformation Polymorphism (SSCP) analysis was used to look for polymorphisms segregating with gPRA in the English cocker spaniel, Labrador retriever, miniature poodle, miniature long-haired dachshund, Tibetan terrier, miniature schnauzer, Cardigan Welsh corgi, and Irish wolfhound breeds. Further investigation involved DNA sequencing and Restriction Fragment Length Polymorphism (RFLP) analysis. My studies revealed the presence of three polymorphisms; an A>G transition in the promoter region; a C>T transition in codon 210, exon 2; and a C>T transition in codon 254, exon 2. None segregated with disease phenotype. Haplotype analysis identified four Rom-1 alleles, three of which were widespread across the canine population: the fourth was seen only in the miniature long-haired dachshund. My results indicate that Rom-1 is unlikely to be a cause of gPRA in the breeds of dog examined. Two feline retinal genes were cloned; Rome-1 and phosphodiesterase gamma subunit (PDEG) a visual transduction cascade gene. Both were investigated as candidates for early onset gPRA in the Abyssinian cat. A conservative amino acid polymorphism in Rom-1, and an intronic polymorphism in PDEG, allowed me to exclude each gene as a cause of gPRA in an Abyssinian pedigree, by segregation analysis of the polymorphisms within the pedigree.