In other species: taurine cattle

Categories: Vision / eye phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 262300 (trait) , 605080 (gene)

Links to MONDO diseases:

• MONDO:0009875: achromatopsia 3

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2002

Cross-species summary: This disorder has been initially renamed in OMIA on the basis of the review by Miyadera et al. (2012). In 2021, entries for Achromatopsia (cone degeneration, hemeralopia), AMAL (OMIA 001365-9615) and Achromatopsia (cone degeneration, hemeralopia), GSPT (OMIA 001676-9615) were merged and renamed 'Achromatopsia-3, CNGB3-related'.

Species-specific name: cone degeneration

Species-specific symbol: cd^AMAL, cd^GSPT

Mapping: Sidjanin et al. (2002) conducted a genome scan with microsatellites, and identified one microsatellite on CFA29, namely C29.002, completely linked to the disorder locus, with recombination fraction = 0 at a LOD score of 24.68.

Molecular basis: A causative mutation for this disorder was identified via a comparative positional cloning approach. First, as described in the Mapping section, a genome scan showed that the disorder locus is in a region of chromosome CFA29. The homologous region of the human genome (HSA8q21-22) contains the gene for cyclic nucleotide-gated channel β-subunit (CNBG3), mutations in which cause a very similar disorder in humans (see the OMIM entry above). Sequencing of this strong comparative positional candidate gene enabled the same authors to report that this disorder in Alaskan Malamute [AM]-derived dogs is due to a "deletion removing all exons of canine CNGB3", and in German Short-hair Pointers [GS] due to a "missense mutation in exon 6 (D262N, nucleotide 784) within a conserved region of" the CNGB3 gene, which encodes cyclic nucleotide-gated channel beta-subunit.

Interestingly, Yeh et al. (2013) reported homozygosity for exactly the same deletion variant observed in the Alaskan Malamutes in affected dogs of the miniature Australian Shepherd [MAS] breed; and heterozygosity for exactly the same deletion mutation in two other breeds (Siberian husky and Alaskan sled dogs). Importantly, these same authors concluded "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."

Breeds: Alaskan Malamute, Alaskan Sled Dog, Miniature Australian shepherd, Siberian Husky.

Associated gene: