Strategies for identification of mutations causing hereditary retinal diseases in dogs: Evaluation of opsin as a candidate gene

Abstract

Progressive retinal atrophy (PRA), like retinitis pigmentosa (RP) in man, represents a clinical classification grouping together a variety of hereditary diseases of the visual cells which have broadly similar clinical characteristics. At least six distinct autosomal recessive and one X-linked retinal disease locus have been identified. As one of the strategies to look for the gene defect causing the different forms of PRA, we are examining first the most promising candidate genes. These include those coding for photoreceptor-specific structural proteins and enzymes of the phototransduction pathway, especially those reported to cause RP. Preeminent among these candidates is the gene for rod opsin, in which multiple causative mutations have been identified in both dominant and recessive forms of RP. In addition, mutations in this gene are also causally associated with congenital stationary night blindness (CSNB) in man. We have used two strategies to examine the rod opsin gene for association with inherited retinal disease in dogs: (1) linkage to determine cosegregation of the disease locus with an intragenic polymorphic marker in the opsin gene in those breeds where suitable informative pedigrees were available; and (2) scanning the coding sequence of the gene in cases where only a limited number of affected or obligate heterozygous samples were available for a breed. We conclude that mutations in the rod opsin gene are not associated with PRA or CSNB in the 11 different dog breeds tested.