OMIA 001365-9615 : Achromatopsia (cone degeneration, hemeralopia), AMAL in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 262300

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 renamed in OMIA on the basis of the review by Miyadera et al. (2012)

Species-specific name: cone degeneration

Species-specific symbol: cd^AMAL

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".

Interestingly, Yeh et al. (2013) reported homozygosity for exactly the same deletion mutation 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:

Symbol Description Species Chr Location OMIA gene details page Other Links
CNGB3 cyclic nucleotide gated channel beta 3 Canis lupus familiaris 29 NC_006611.3 (32992715..32744946) CNGB3 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the required column headers

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Alaskan Malamute Miniature Australian shepherd Achromatopsia (cone degeneration, hemeralopia), AMAL CNGB3 deletion, gross (>20) "deletion removing all exons of canine CNGB3" 2002 12140185

References


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.
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 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.
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.
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.
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.

Edit History


  • 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