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.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

“…Although no functional characterization of these mice has been reported, histological analysis revealed some morphological features of RP (e.g., reduced number of photoreceptors, apoptotic death of retinal cells). A naturally occurring Cnga1 mutation has been recently identified in a Shetland sheepdog breed with progressive retinal atrophy [ 54 ]. However, functional characterization of the retinal phenotype is still missing.…”

A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications

“…Progressive retinal atrophy (PRA) is a collective term that describes a multitude of inherited retinal degenerations observed in dogs and cats. PRA is often considered to be the canine equivalent of retinitis pigmentosa (RP) which occurs in humans [ 11 ]. Interestingly this group of inherited retinal degenerations is diverse and affect a congregation of genes, they do not follow a single model of inheritance, but have many variations, and the age of onset ranges greatly.…”

Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development—Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus

“…Genome wide association studies in dogs have been highly successful owing to long-range linkage disequilibrium (LD), available SNP genotyping tools and a robust genome assembly [ 17 , 18 ]. There are many examples of successful GWAS in dogs for Mendelian traits [ 17 , 19 , 20 , 21 , 22 , 23 ] as well as for more complex traits [ 24 , 25 , 26 , 27 , 28 ]. In addition, across-breed mapping studies by us and others have successfully identified biologically relevant loci for several traits and related diseases that are fixed within breeds [ 29 , 30 , 31 , 32 ].…”