Screening of the arrestin gene in dogs afflicted with generalized progressive retinal atrophy

Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequence analyses we screened affected and unaffected dogs of 23 breeds with presumed autosomal recessively (ar) transmitted gPRA. In the coding region of the SAG gene 12 nucleotide exchanges were identified, 5 of which lead to amino acid substitutions (H14C; A111V; A113T; D259T; A379E). 7 other exonic substitutions represent silent polymorphisms (C132C; Q199Q; H225H; V247V; P264P; T288T and L293L). 16 additional sequence variations were observed in intronic regions of different dog breeds.In several breeds, these polymorphisms were found in homozygous state in unaffected and in heterozygous state in affected animals. Consequently these informative substitutions provide evidence to exclude mutations in the SAG gene as causing retinal degeneration in 14 of the 23 dog breeds with presumed ar transmitted gPRA.gPRA is usually inherited as an ar blinding disorder with different ages of onset and variable rate of progression observed in more than 100 dog breeds. Typically, gPRA commences with degeneration of the rod photoreceptors. Initial signs include night blindness whereas progression involves the cones and the central vision [1,2]. The human equivalent of canine gPRA is termed retinitis pigmentosa (RP). RP comprises a large and genetically heterogeneous group of blinding disorders. RP may be inherited in an ar, dominant, X-linked, digenic or maternal mode [3-7]. Similarly in dogs, at least 4 genes were identified so far as causing gPRA in 6 breeds. All of these genes encode photoreceptor specific proteins involved in the visual transduction cascade including the β-subunit of the cGMP-specific phosphodiesterase (PDE6B) in Irish Setters and Sloughis [8,9] as well as the α-subunit of the cGMP-specific phosphodiesterase (PDE6A) in Cardigan Welsh Corgis [10]. A missense mutation was detected in the PDC gene that may be associated with photoreceptor dysplasia, a form of gPRA in the M