Also known as: Wilson's disease
Affected genes: ATP7B, ATP7A
Inheritance :
Incomplete dominant for ATP7B
Chr X-linked for ATP7A
Mutations :
-ATP7B: chr22:115112 G>A
-ATP7A: ChrX:60279238 C>T
Breeds suitable for testing : Doberman Pinscher
Symptoms:
Copper toxicosis is a metabolic disease leading to chronic liver failure. Affected dogs have a reduced ability to excrete dietary copper, resulting in storage in organs such as the liver, which can lead to liver damage and cirrhosis.
ATP7B is associated with copper accumulation and its inheritance is autosomal dominant incomplete meaning that a single copy of the mutation may have an increased risk of developing the disease, but to a lesser extent than dogs carrying 2 copies of the mutation.
ATP7A is associated with a protective effect against this accumulation, and its transmission is X-linked. This variant is therefore beneficial in males (1 copy). Females with a single copy have a lower protective effect than females with 2 copies.
It is important to note:
(1) If there are no copies of the mutation on the ATP7B variant, the results for ATP7A should be ignored as they will have no effect.
(2) Additional factors (genetic and environmental) probably play a further role in the development of the disease and vary from breed to breed.
Reference:
Wu, X., den Boer, E.R., Vos-Loohuis, M., Steenbeek, F.G.V., Monroe, G.R., Nijman, I.J., Leegwater, P.A.J., Fieten, H. :
Investigation of genetic modifiers of copper toxicosis in Labrador Retrievers. Life (Basel) 10:266, 2020.
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.