Abstract
BackgroundAchromatopsia is an autosomal recessive disease characterized by the loss of cone photoreceptor function that results in day-blindness, total colorblindness, and decreased central visual acuity. The most common causes for the disease are mutations in the CNGB3 gene, coding for the beta subunit of the cyclic nucleotide-gated channels in cones. CNGB3-achromatopsia, or cone degeneration (cd), is also known to occur in two canine breeds, the Alaskan malamute (AM) and the German shorthaired pointer.ResultsHere we report an in-depth characterization of the achromatopsia phenotype in a new canine breed, the miniature Australian shepherd (MAS). Genotyping revealed that the dog was homozygous for a complete genomic deletion of the CNGB3 gene, as has been previously observed in the AM. Identical breakpoints on chromosome 29 were identified in both the affected AM and MAS with a resulting deletion of 404,820 bp. Pooled DNA samples of unrelated purebred Australian shepherd, MAS, Siberian husky, Samoyed and Alaskan sled dogs were screened for the presence of the affected allele; one Siberian husky and three Alaskan sled dogs were identified as carriers. The affected chromosomes from the AM, MAS, and Siberian husky were genotyped for 147 SNPs in a 3.93 Mb interval within the cd locus. An identical shared affected haplotype, 0.5 Mb long, was observed in all three breeds and defined the minimal linkage disequilibrium (LD) across breeds. This supports the idea that the mutated allele was identical by descent (IBD).ConclusionWe report the occurrence of CNGB3-achromatopsia in a new canine breed, the MAS. The CNGB3-deletion allele previously described in the AM was also observed in a homozygous state in the affected MAS, as well as in a heterozygous carrier state in a Siberian husky and Alaskan sled dogs. All affected alleles were shown to be IBD, strongly suggesting an affected founder effect. Since the MAS is not known to be genetically related to the AM, other breeds may potentially carry the same cd-allele and be affected by achromatopsia.
Highlights
Achromatopsia is an autosomal recessive disease characterized by the loss of cone photoreceptor function that results in day-blindness, total colorblindness, and decreased central visual acuity
In the Alaskan malamute (AM), it is caused by a genomic deletion of the entire Beta subunits of cone cyclic-nucleotide gated channel (CNGB3) gene, while in the German shorthaired pointer it results from a missense mutation in exon 6 [13]
One is the D262N missense mutation in German shorthaired pointers, while the other is a genomic deletion of CNGB3 found in the AM [13]
Summary
Achromatopsia is an autosomal recessive disease characterized by the loss of cone photoreceptor function that results in day-blindness, total colorblindness, and decreased central visual acuity. CNGB3-achromatopsia, or cone degeneration (cd), is known to occur in two canine breeds, the Alaskan malamute (AM) and the German shorthaired pointer. In the Alaskan malamute (AM), it is caused by a genomic deletion of the entire CNGB3 gene, while in the German shorthaired pointer it results from a missense mutation in exon 6 [13]. Both of these genetic defects are functional null mutations, and the phenotypic manifestations resemble those observed in human patients [14]. The length of the deletion and the inclusion of other adjacent genes were not identified, which resulted in an inability to identify carrier dogs [13]
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