€57,48 €47,50 excl. VAT
This test is for a mutation on the ATP7B gene.
10 working days
From €5,95 shipping and administration per order (incl. VAT)
Specifications
| Breeds | Huntaway, New Zealand Heading Dog, Australian Cobberdog, Australian Labradoodle, Bedlington Terrier, Cavalier King Charles Spaniel, Dalmatian, Doberman, Labrador Retriever |
|---|---|
| Gene | |
| Chromosome | 22 |
| Mutation | c.4358G>A |
| Organ | |
| Specimen | Swab, Blood EDTA, Blood Heparin, Semen, Tissue |
| Mode of Inheritance | Unknown |
| Also known as | CT; Copper toxicosis; Copper storage disease |
General information
This test is for a mutation on the ATP7B gene. The ATP7B gene is associated with an increased risk of developing copper toxicosis in several dog breeds. Copper toxicosis is sometimes also called Wilson Disease. In Labrador Retrievers the ATP7B gene interacts with two other genes, ATP7A and RETN. A mutation in ATP7A has been found to be protective, and in one study, carrying one or two copies of a mutation in RETN was associated with lower copper values in the liver in Labradors. Follow-up studies have not replicated these findings, so the RETN variant may be neutral rather than protective. In Labradors and related breeds we recommend testing the three variants together.
Clinical features
Copper levels in the body are regulated by both dietary intake and secretion from specific organs, such as the bile ducts. Multiple genes play crucial roles in maintaining optimal copper levels. A mutation in the ATP7B gene is associated with increased copper accumulation, leading to Wilson Disease, also called copper toxicosis or copper related hepatopathy. Conversely, mutations in modifier genes ATP7A or RETN appear to confer a protective effect against copper buildup in the liver, formerly known as Menkes Disease. Currently, these modifier genes are only relevant for Labrador Retrievers. However, the ATP7B mutation can cause clinical symptoms in several breeds.
The ATP7B mutation has an incomplete dominant mode of inheritance. Dogs carrying one copy of the mutation have a somewhat increased risk of developing symptoms of copper toxicosis, while those affected with two copies have a much higher risk. This is because dysfunction of the ATP7B protein disrupts copper transport, potentially leading to liver cirrhosis. Symptom onset can be very subtle, and the age of onset varies between individuals, often 5-7 years of age. Disease severity is also influenced by dietary copper intake levels, and by genetic variants with a protective effect.
In Labrador Retrievers, the a mutation in the gene ATP7A can mitigate copper levels, thereby reducing the risk and severity of Copper Toxicosis. Dogs carrying or affected by mutations in ATP7A are thus afforded some protection against copper toxicosis in the presence of an ATP7B mutation. The RETN mutation may be protective or neutral. The modifiers do not confer benefits in the absence of an ATP7B mutation. Consequently, testing Labradors and related breeds for all three mutations together is recommended.
Additional information
In the context of breeding, priority should be given to avoiding copper toxicosis using the ATP7B test. If a dog carrying or affected by two copies of the ATP7B mutation is used for breeding, the ATP7A protective allele should also be taken into consideration, but should not otherwise be selected for or against. At the current time, it is recommended that the RETN potential modifier mutation should not be considered in breeding decisions.
Although copper toxicosis in Bedlington Terriers was historically caused by a mutation in COMMD1, selection against this mutation has greatly reduced its prevalence in the breed. However, the ATP7B mutation was already present at low frequency and appears to have been inadvertently selected for. As a result, the ATP7B mutation is now more common than in the past and is responsible for most cases of copper toxicosis in modern Bedlington Terriers.
References
Pubmed ID: 26747866
Year published: 2016
Omia ID: 1071
Omia variant ID: