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Copper Toxicosis Labrador Retriever Type
| Acronym: | CTOX-A |
| Gene: | ATP7A |
| Mutation: | c.980C>T |
| Inheritance: | X-linked incomplete dominant |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Copper Toxicosis is a complex genetic disorder found in Labrador retriever dogs characterized by a gradual accumulation of copper in the hepatocytes, a cell type found in the liver. Copper accumulation may result in chronic hepatitis and liver cirrhosis which is a life-threatening condition, not only in dogs but also in other animals and humans. There is no cure for copper-associated hepatitis, but it could be controlled by a low-copper diet during the early stage of the disease if it is detected early enough. Affected dogs often start to show signs of the disease in early adulthood and they include cerebral degeneration, connective tissue abnormalities, coarse hair, and a failure to thrive. In Labrador retriever dogs, copper toxicosis was shown to be associated with a mutation in the ATP7A gene. ATP7A is a copper transporting ATPase that plays a role in copper transportation and when mutated causes downregulation of copper absorption by the small intestinal and increases copper accumulation in the hepatocytes.
This copper-metabolism disruption found in labrador retriever dogs is inherited as an X-linked trait meaning the specific mutation that causes the disease is located on the sex chromosome. Since male dogs have just one X chromosome, if they carry the mutation, they will develop the disease. Female dogs have two X chromosomes and hence, dogs with both mutated genes will develop the disease, and dogs with only one copy of the mutated gene will act as carriers. Early genetic testing can help identify dogs that carry the gene with the specific mutation and prevent their further breeding by the proper selection of mating pairs.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (female) or hemizygous state (male) (i.e. only healthy allele on X chromosome). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.**It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has mutated allele in homozygous state (female) or hemizygous state (male) (i.e. only mutated allele on X chromosome). It is likely the animal will experience a genetic disorder due to this mutation.**It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Takanosu, M., Suzuki, K. (2022). Genotype frequency of ATP7A and ATP7B mutation-related copper-associated hepatitis in a Japanese guide dog Labrador retriever population. The Journal of veterinary medical science, 84(1), 16–19. https://doi.org/10.1292/jvms.21-0369
Wu, X., den Boer, E. R., Vos-Loohuis, M., Steenbeek, F., Monroe, G. R., Nijman, I. J., Leegwater, P., Fieten, H. (2020). Investigation of Genetic Modifiers of Copper Toxicosis in Labrador Retrievers. Life (Basel, Switzerland), 10(11), 266. https://doi.org/10.3390/life10110266
Fieten, H., Gill, Y., Martin, A. J., Concilli, M., Dirksen, K., van Steenbeek, F. G., Spee, B., van den Ingh, T. S., Martens, E. C., Festa, P., Chesi, G., van de Sluis, B., Houwen, R. H., Watson, A. L., Aulchenko, Y. S., Hodgkinson, V. L., Zhu, S., Petris, M. J., Polishchuk, R. S., Leegwater, P. A., … Rothuizen, J. (2016). The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders. Disease models & mechanisms, 9(1), 25–38. https://doi.org/10.1242/dmm.020263