Prevalence of the exon 2 deletion of the COMMD1 gene in Australian Bedlington terriers

Abstract

Inherited copper toxicosis in Bedlington terriers is a chronic progressive hepatic disease caused by an abnormal accumulation of copper due to genetic derangement in the biliary copper excretion pathway. In this study, we screened a group of Australian Bedlington terriers for a previously identified mutation, an exon 2 deletion in the COMMD1 gene. The DNA samples used in this study were collected from 149 Bedlington terriers (60 males and 89 females), aged between four weeks to 13 years from eight different pedigrees obtained over a period of three years. We found 60 dogs (40%) were homozygous wild type, 42 dogs (28%) were homozygous mutant, and 47 dogs (32%) were heterozygous for the deletion of exon 2 in the COMMD1 gene. Not only this reports the first large scale genetic screening of the known COMMD1 mutation in Bedlington terriers, but our results also indicate a high prevalence of the COMMD1 mutation in Bedlington terriers that might also be useful as a marker of copper toxicosis. Inherited copper toxicosis was first identified in Bedlington terrier in USA, in 1975 (Hardy et al. 1975) and has since been reported in other countries including Australia (Eriksson 1983; Robertson et al. 1983; Kelly et al. 1984). This disease is an inherited autosomal recessive disorder characterized by a progressive accumulation of copper, predominantly in the liver (Hardy 1984; Johnson et al. 1980). The main pathogenesis of the copper toxicosis in Bedlington terrier appears to be related to the reduced biliary excretion of stored copper resulting from a genetic derangement in copper metabolism (Hardy 1984; Hyun and Filippich 2004). A mutation resulting in the deletion of exon 2 in the COMMD1 (formerly known asMurr1) gene was found to be responsible for copper toxicosis in a subpopulation of Bedlington terriers (Van de Sluis et al. 2002)