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Copper Toxicosis Bedlington Terrier Type (CT)
| Acronym: | CT |
| Gene: | COMMD1 / MURR1 |
| Mutation: | chr10 39.7Kb deletion |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Copper Toxicosis Bedlington Terrier Type (CT) is a genetic disorder of copper accumulation unique to the Bedlington terrier dog breed. Different hereditary forms of copper toxicosis have been identified in humans and dogs. In dogs, other than Bedlington Terriers, CT affected breeds are also West Highland White terrier, Skye terrier, Dalmatian, Dobermann, and Labrador retriever. Human equivalent with similar phenotypes of this canine disorder is Menkes disease, Wilson’s disease, Indian childhood cirrhosis, endemic Tyrolean infantile cirrhosis, and idiopathic copper toxicosis. In the body, copper can be found as a trace element, but in certain excess concentrations it can be highly toxic and therefore its concentrations are tightly regulated. Copper has an essential role in various biological processes, such as mitochondrial respiration, antioxidant defense, connective tissue formation, neurotransmitter synthesis, iron metabolism, and pigmentation. Copper is absorbed in the small intestine via specific transporters. In the blood, it is found bound in complexes with small molecules, such as histidine and serum proteins. In such form, it will be transported to the liver, its primary storage location. There have been two copper carrier proteins identified, which have been connected with copper deficiency when defective.
Copper Toxicosis Bedlington Terrier Type (CT) is characterized by the accumulation of copper in the liver as a result of inefficient excretion of copper via the bile. This leads to chronic hepatitis and in the most severe stage of the disease, cirrhosis. In the first stage of the disease, clinical signs are present in the body of the dog but cannot be detected by any visual symptoms in the dog’s behavior or external appearance. As the disorder progresses, hepatic necrosis (death of liver tissue) develops and the first symptoms can be observed. These are lethargy, depression, anorexia, weight loss, vomiting, diarrhea, excessive thirst and urination, yellowish discoloration of the skin, abnormalities in the stool, and nervous system dysfunction. In Bedlington Terrier massive accumulation of copper in the liver has been measured, the highest that has been recognized in any dog breed. Copper Toxicosis Bedlington Terrier Type (CT) is caused by a mutation in the COMMD1 gene (Copper Metabolism gene MURR1 containing Domain 1). The gene was originally named the MURR1 gene, but upon the discovery of nine other proteins related to the MURR1 protein, it was renamed to its current name. Prevalence of the mutation in the Bedlington Terrier breed is predicted to be high, ranging from 25 to 46% in different populations.
The genetic cause of CT in other breeds is unconfirmed and the mode of inheritance is unknown. CT in Bedlington Terrier is inherited in an autosomal recessive manner. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of copper toxicosis. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
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 (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not 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 two copies of mutation alleles affecting the gene. 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.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Van De Sluis, B. et al. (2002): Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum Mol Genet. 2002 Jan 15; 11 (2): 165-73.
Fieten, H. et al. (2012): Canine models of copper toxicosis for understanding mammalian copper metabolism. Mamm Genome 23: 62-75.
Forman, O. P. et al. (2005): Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Animal Genetics, 36, 497–501
Lee, SA. et al. (2007): Prevalence of the exon 2 deletion of the COMMD1 gene in Australian Bedlington terriers. Journal of Genetics, Vol. 86, No. 3, December 2007