Canine Rod Cone Dysplasia Type 2 (rcd2) Is the Canine Ortholog of Human and Murine RD3

Abstract

Purpose: : To identify the gene and mutation responsible for rcd2.

Methods: : Selected dogs from an experimental mixed-breed colony, derived using multiple rcd2-affected founders, were genotyped for SNP markers in the rcd2 non-recombinant region on CFA7, flanked by markers FH2226 and FH3972, in order to identify haplotypes cosegregating with the mutant allele. Candidate genes within the minimal linkage disequilibrium region were evaluated to identify potentially causative mutations.

Results: : The minimal linkage disequilibrium region, where all affected founders shared the same haplotype, was found to be approximately 230 kb. This interval included only 3 recognized genes, one of these (c1orf36) was simultaneously and independently identified as the causative locus for rd3 in mouse and early-onset retinopathy in humans. An insertion mutation that causes a frame-shift in the open reading frame was identified within the coding sequence of the canine rd3 gene and is likely to be the cause of the rcd2 phenotype.

Conclusions: : Canine rod cone dysplasia type 2 (rcd2) is the canine ortholog of human and murine RD3, and is thus validated as a model for evaluation of potential therapies, and for studies of the mechanism of this form of retinal degeneration.

Keywords: retinal degenerations: hereditary • genetics • retinal degenerations: cell biology