Copper toxicosis in Bedlington terriers is associated with multiple independent genetic variants

Abstract

AbstractBackgroundBedlington terrier copper toxicosis (CT) is due to a homozygous exon deletion inCOMMD1. CT also occurs in Bedlingtons lacking this deletion. An association with twoABCA12single nuceotide polymorphism (SNP) splice variants was reported. Labrador retriever CT is associated with a missense mutation inATP7B, and with a protective mutation inATP7A.MethodsLiver and DNA samples from 24 affected and 10 unaffected Bedlingtons were assessed for copper and genetic variants. Allelic frequencies were compared. TheATP7Bmutation frequency was investigated in 144 dogs of other breeds.ResultsTheABCA12SNPs showed no differences between groups. TheCOMMD1deletion was less frequent in unaffected than in affected dogs and in affected dogs post‐2001 than pre‐2001. TheATP7Bmutation was more frequent in affected than unaffected Bedlingtons. Thirty‐five of 144 dogs of other breeds were homo‐ or heterozygous for theATP7Bmutation. TheATP7Amutation was absent from Bedlingtons.LimitationsClinical information and qualitative copper measurements were unavailable for most dogs.ConclusionTheCOMMD1deletion remains present in Bedlington terriers but is no longer the primary cause of CT.ABCA12SNPs were not associated with CT. TheATP7B:c.4358G>Amutation was significantly associated with Bedlington CT and was more common in dogs of this breed than in the 144 dogs of other breeds.