Embark for Breeder’s full panel DNA test now includes three new variants for Copper Toxicosis. The first variant, APT7B, is the harmful (accumulating) variant, and the two beneficial (attenuating) variants are ATP7A and RETN. Embark is the only dog DNA company that offers the RETN test.
What is Copper Toxicosis?
Copper Toxicosis is an accumulation of copper in the liver. Affected dogs have difficulty excreting excess copper from their liver, which allows copper to build up until the liver eventually begins failing. Multiple genetic and environmental (particularly dietary) factors also contribute to the development of this condition.
Clinical signs can range from none to severe, including include weight loss, vomiting, jaundice, fluid-filled abdomen, and neurologic signs. Females are more impacted than males. Adult onset is typically between 2 and 7 years of age. Copper Toxicosis is definitively diagnosed through liver biopsy and copper quantification.
How are Copper Toxicosis variants inherited?
ATP7B (Accumulating variant)
The mode of inheritance for ATP7B is incomplete dominance, meaning that one or two copies of this gene can cause the disorder. However, it is incompletely penetrant, which means not all dogs with one or two copies of the variant will develop the disease. Dogs with one copy have a significantly lower disease risk than dogs with two copies.
ATP7A (Attenuating variant)
The mode of inheritance for ATP7A is complex (X-linked). This variant has been shown to decrease copper accumulation in dogs with one or two copies of the ATP7B variant. The ATP7A gene is most beneficial in males with one copy. Females with one copy likely have less benefit than females with two copies. It is not completely protective in either sex. Dogs with one or two copies of the ATP7A variant but no copies of ATP7B will not have copper levels low enough to pose any health risk.
RETN (Attenuating variant)
The mode of inheritance for RETN is complex. One or two copies of this variant may reduce the accumulation of copper in the liver of Labrador Retrievers with one or two copies of the APT7B variant and may help reduce disease severity. Dogs with one or two copies of the RETN variant but no copies of ATP7B will not have copper levels low enough to pose any health risk.
What breeds are affected?
Breeds with known genetic variants include Labrador Retrievers (ATP7B, ATP7A, and RETN) and Doberman Pinschers (ATP7B and ATP7A).
How can Copper Toxicosis test results be used in a breeding program?
Knowing the number of copies of the variants in a breeding dog’s ATP7B, ATP7A, and RETN genes is vital for selecting a breeding strategy.
One or two copies of the ATP7B variant and no copies of ATP7A and RETN
If a breeding dog has one or two copies of the ATP7B variant but no copies of ATP7A or RETN, a breeder should consider the following.
The ATP7B variant (which increases the risk of copper toxicosis) is often found at high frequencies in Labrador Retriever and Doberman Pinscher populations and, therefore, likely cannot be eliminated completely.
Because dogs with one copy of this variant are at lower risk for disease than dogs with two copies, dogs with one or two copies should be bred to clear dogs (no copies) when possible. This breeding scenario may produce dogs with one copy of ATP7B but will not produce any dogs with two copies.
The variants in the ATP7A and RETN genes may help mitigate the effects of the APT7B variant in dogs with copper accumulation. Ideally, finding a mate with one or both of these beneficial variants may help decrease the effect of the ATP7B variant in their offspring.
One or two copies of the ATP7B variant and one or two copies of ATP7A and/or RETN
If your dog has one or two copies of ATP7B and one or two copies of ATP7A and/or RETN, then consider the following. The same logic applies when considering the ATP7B variant; dogs with one or two copies should be bred to dogs with no copies when possible.
If a dog also has the variants in the ATP7A and/or RETN genes, it may help mitigate the effects of the APT7B variant in dogs with copper accumulation. Having one or two copies of ATP7A and/or RETN may also decrease the effect of the variant in the ATP7B gene in their offspring, which they will help pass on.
No ATP7B variant and one or two copies of the ATP7A and/or RETN variants
If a breeding dog has no copies of the ATP7B variant, you can ignore the results for the ATP7A and RETN variants. Because the ATP7A and RETN variants do not have any clinical effect in the absence of the ATP7B variant, breeding decisions do not need to be made based on these two results alone. We recommend considering other factors such as temperament, structure, and other health testing results when deciding whether to breed.
Citations: Feiten et al 2016, Wu et al 2019, Langlois et al 2022, Wu et al 2020
