OMIA:001365-9615 : Achromatopsia-3, CNGB3-related in Canis lupus familiaris
In other species: 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:
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.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CNGB3||cyclic nucleotide gated channel beta 3||Canis lupus familiaris||29||NC_051833.1 (33163070..32900394)||CNGB3||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|631||Alaskan Malamute Miniature Australian shepherd||Achromatopsia (cone degeneration, hemeralopia), AMAL||CNGB3||cd^AMAL||deletion, gross (>20)||Naturally occurring variant||29||"deletion removing all exons of canine CNGB3"||2002||12140185|
|27||German Shorthaired Pointer||Achromatopsia (cone degeneration, hemeralopia), GSPT||CNGB3||cd^GSPT||missense||Naturally occurring variant||CanFam3.1||29||g.32837065C>T||c.784G>A||p.(D262N)||2002||12140185||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool 30 Dec 2020 Chromosome corrected, thanks to Angelica K Kallenberg|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Park, S.A., Rhodes, J., Iwabe, S., Ying, G.S., Pan, W., Huang, J., Komáromy, A.M. :|
|Quantitative and qualitative characterization of retinal dystrophies in canine models of inherited retinal diseases using spectral domain optical coherence tomography (SD-OCT). Exp Eye Res :109106, 2022. Pubmed reference: 35588783 . DOI: 10.1016/j.exer.2022.109106.|
|2020||Switonski, M. :|
|Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61:179-186, 2020. Pubmed reference: 32189222 . DOI: 10.1007/s13353-020-00554-8.|
|2017||Ye, G.J., Komáromy, A.M., Zeiss, C., Calcedo, R., Harman, C.D., Koehl, K.L., Stewart, G.A., Iwabe, S., Chiodo, V.A., Hauswirth, W.W., Aguirre, G.D., Chulay, J.D. :|
|Safety and efficacy of AAV5 vectors expressing human or canine CNGB3 in CNGB3-mutant dogs. Hum Gene Ther Clin Dev 28:197-207, 2017. Pubmed reference: 29020838 . DOI: 10.1089/humc.2017.125.|
|2016||Dixon, C.J. :|
|Achromatopsia in three sibling Labrador Retrievers in the UK. Vet Ophthalmol 19:68-72, 2016. Pubmed reference: 25752464 . DOI: 10.1111/vop.12265.|
|2013||Komáromy, A.M., Rowlan, J.S., Corr, A.T., Reinstein, S.L., Boye, S.L., Cooper, A.E., Gonzalez, A., Levy, B., Wen, R., Hauswirth, W.W., Beltran, W.A., Aguirre, G.D. :|
|Transient Photoreceptor Deconstruction by CNTF Enhances rAAV-Mediated Cone Functional Rescue in Late Stage CNGB3-Achromatopsia. Mol Ther :, 2013. Pubmed reference: 23568263 . DOI: 10.1038/mt.2013.50.|
|Yeh, C.Y., Goldstein, O., Kukekova, A.V., Holley, D., Knollinger, A.M., Huson, H.J., Pearce-Kelling, S.E., Acland, G.M., Komáromy, A.M. :|
|Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia. BMC Genet 14:27, 2013. Pubmed reference: 23601474 . DOI: 10.1186/1471-2156-14-27.|
|2012||Miyadera, K., Acland, G.M., Aguirre, G.D. :|
|Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099 . DOI: 10.1007/s00335-011-9361-3.|
|2010||Komáromy, A.M., Alexander, J.J., Rowlan, J.S., Garcia, M.M., Chiodo, V.A., Kaya, A., Tanaka, J.C., Acland, G.M., Hauswirth, W.W., Aguirre, G.D. :|
|Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet 19:2581-93, 2010. Pubmed reference: 20378608 . DOI: 10.1093/hmg/ddq136.|
|Komaromy, AM. :|
|Day blind sheep and the importance of large animal disease models. Vet J 185:241-242, 2010. Pubmed reference: 20061167 . DOI: 10.1016/j.tvjl.2009.07.007.|
|2006||Seddon, JM., Hampson, EC., Smith, RI., Hughes, IP. :|
|Genetic heterogeneity of day blindness in Alaskan Malamutes. Anim Genet 37:407-10, 2006. Pubmed reference: 16879359 . DOI: 10.1111/j.1365-2052.2006.01484.x.|
|2002||Sidjanin, D.J., Lowe, J.K., McElwee, J.L., Milne, B.S., Phippen, T.M., Sargan, D.R., Aguirre, G.D., Acland, G.M., Ostrander, E.A. :|
|Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3 Human Molecular Genetics 11:1823-33, 2002. Pubmed reference: 12140185 .|
|1971||Rubin, L.F. :|
|Clinical features of hemeralopia in the adult Alaskan malamute. J Am Vet Med Assoc 158:1696-8, 1971. Pubmed reference: 5314319 .|
|Rubin, L.F. :|
|Hemeralopia in Alaskan Malamute pups. J Am Vet Med Assoc 158:1699-701, 1971. Pubmed reference: 5314320 .|
|1967||Rubin, L.F., Bourns, T.K.R., Lord, L.H. :|
|Hemeralopia in dogs: heredity of hemeralopia in Alaskan Malamute American Journal of Veterinary Research 28:355-357, 1967. Pubmed reference: 5298491 .|
- Created by Frank Nicholas on 12 Sep 2005
- Changed by Frank Nicholas on 07 Dec 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 19 Sep 2012
- Changed by Frank Nicholas on 25 Apr 2013
- Changed by Imke Tammen2 on 24 Dec 2021