Cone Degeneration

Quick Summary

Loss of cone function due to cone degeneration results in day-blindness and decreased visual acuity. There are 2 known mutations of the CNGB3 gene that cause canine cone degeneration day-blindness in dogs.

Phenotype: Loss of cone function due to cone degeneration results in day-blindness and decreased visual acuity, with signs of the defect appearing between 8 and 12 weeks when retinal development is completed in dogs. Typically, affected dogs become increasingly photophobic as exposure to bright light is irritating and painful. Vision in low light conditions remains normal.

Mode of Inheritance: Autosomal recessive

Alleles: N = Normal, CD1 = CNGB3 cone degeneration variant (gene segment deletion), CD2 = CNGB3 cone degeneration variant (SNP nucleotide change)

Breeds appropriate for testing: Alaskan Malamute, Alaskan Sled Dog, Australian Shepherd, German Shorthaired Pointer, Miniature Australian Shepherd, Siberian Husky

Explanation of Results:

  • Dogs with N/N genotype will not have these types of cone degeneration.
  • Dogs with N/CD1 or N/CD2 genotype will not have these types of cone degeneration, but are carriers. They will transmit a cone degeneration variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% cone degeneration-affected puppies.
  • Dogs with CD1/CD2, CD1/CD1, or CD2/CD2 genotype will have cone degeneration, an inherited disease that causes day-blindness. 

Results of this test can be submitted to the OFA (Orthopedic Foundation for Animals)

Price

$50 one test per animal
$30 as additional test (same animal)
$45 for 3 or more dogs

Additional Details

There are 2 known mutations of the CNGB3 gene that cause canine cone degeneration (CD) day-blindness in dogs. One affects Miniature Australian Shepherd, Alaskan sled dogs, and related breeds; the other is found in German Shorthaired Pointers and Alaskan sled dogs.

One form of cone degeneration (CD1) or CNGB3-achromatopsia results from the deletion of a 400,000 bases long genomic segment that includes the CNGB3 gene. The loss of CNGB3, a key component for normal vision, causes loss of function of the cones in the eye. This can only be confirmed by electroretinography; ophthalmic exams of affected dogs are not informative as results remain normal. This disease is inherited in an autosomal recessive fashion with both sexes being equally affected. The loss of cone function results in day-blindness and decreased visual acuity, with signs of the defect appearing between 8 and 12 weeks when retinal development is completed in dogs. Typically, affected dogs become increasingly photophobic as exposure to bright light is irritating and painful. Vision in low light conditions remains normal. Dogs with one normal and one deleted gene have normal vision. This defect is found in Alaskan Sled Dogs, Alaskan Malamute, Miniature Australian Shepherd, and Siberian Husky breeds.

Another form of CNGB3 (CD2) is due to a different mutation, a nucleotide change (SNP) in exon 6 of CNGB3, and is found in German Shorthaired Pointers and Alaskan Sled Dogs. This mutation is also an inherited as autosomal recessive and the disease progression and phenotype are similar to CD1. Dogs with 1 copy each of the 2 mutations (compound heterozygotes) are affected.

Genetic testing is recommended for German Shorthaired Pointer, Alaskan Malamute, Miniature Australian Shepherd, Siberian Husky, and Alaskan Sled Dogs breeds. Australian Shepherds may also be at risk.

 

Note: This test is specific for the CNGB3 deletion and CNGB3 SNP known to cause day- blindness in German Shorthaired Pointer, Alaskan Malamute, Miniature Australian Shepherd, Siberian Husky, and Alaskan Sled Dog breeds.
Turnaround Time
3-6 business days

Species

Dog

Type of Test

Results Reported As
Test Result Cone Degeneration
N/N No copies of CNGB3 mutation. Dog is normal.
N/CD1 1 copy of CNGB3 mutation. Dog is normal but is a carrier.
N/CD2 1 copy of CNGB3 mutation. Dog is normal but is a carrier.
CD1/CD2 2 copies of CNGB3 mutations. Dog has day-blindness.
CD1/CD1 2 copies of CNGB3 mutations. Dog has day-blindness.
CD2/CD2 2 copies of CNGB3 mutations. Dog has day-blindness.
References

Sidjanin, D.J., Lowe, J.K., McElwee, J., Milne, B.S., Phippen, T.M., Sargan, D., Aguirre, G.D., Acland, G.M., & Ostrander, E.A. (2002). Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Human Molecular Genetics, 11(16), 1823-1833. doi: 10.1093/hmg/11.16.1823

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. (2013). Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia. BMC Genetics, 14(1):27. doi: 10.1186/1471-2156-14-27