title: Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene.
abstract: Progressive retinal atrophy (PRA) is the collective name of a class of hereditary retinal dystrophies in the dog and is often described as the equivalent of retinitis pigmentosa in humans. PRA is characterized by visual impairment due to degeneration of the photoreceptors in the retina, usually leading to blindness. PRA has been reported in dogs from more than 100 breeds and can be genetically heterogeneous both between and within breeds. The disease can be subdivided by age at onset and rate of progression. Using genome-wide association with 15 Shetland Sheepdog (Sheltie) cases and 14 controls, we identified a novel PRA locus on CFA13 (Praw  = 8.55 × 10(-7) , Pgenome  = 1.7 × 10(-4) ). CNGA1, which is known to be involved in human cases of retinitis pigmentosa, was located within the associated region and was considered a likely candidate gene. Sequencing of this gene identified a 4-bp deletion in exon 9 (c.1752_1755delAACT), leading to a frameshift and a premature stop codon. The study indicated genetic heterogeneity as the mutation was present in all PRA-affected individuals in one large family of Shelties, whereas some other cases in the studied Sheltie population were not associated with this CNGA1 mutation. To our knowledge, this is the first report of a mutation in CNGA1 causing PRA in dogs.
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, NMBU, Postboks 8146 Dep, 0033, Oslo, Norway.
authors.forename: A C
authors.initials: AC
authors.lastname: Wiik
authors.affiliation: Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, NMBU, Postboks 8146 Dep, 0033, Oslo, Norway.
authors.forename: E O
authors.initials: EO
authors.lastname: Ropstad
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 75007, Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Ekesten
authors.affiliation: Aros Veterinär Centrum, Olof Palmes Torg 10, 723 34, Västerås, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Karlstam
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: C M
authors.initials: CM
authors.lastname: Wade
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, NMBU, Postboks 8146 Dep, 0033, Oslo, Norway.
authors.forename: F
authors.initials: F
authors.lastname: Lingaas
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D018389:Codon, Nonsense; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000145:classification / Q000235:genetics*; D016368:Frameshift Mutation; D055106:Genome-Wide Association Study; D005838:Genotype; D020641:Polymorphism, Single Nucleotide; D012162:Retinal Degeneration / Q000235:genetics / Q000662:veterinary*; D012537:Scandinavian and Nordic Countries; D017384:Sequence Deletion
chemical_list: D018389:Codon, Nonsense; D054815:Cyclic Nucleotide-Gated Cation Channels
keywords: PRA; Sheltie; canine; rod-cone degeneration