The canine copper toxicosis locus is not syntenic with ATP7B or ATX1 and maps to a region showing homology to human 2p21

• Published in: Mammalian genome Vol. 10; no. 7; pp. 753 - 756
• Main Authors: Dagenais, S L, Guevara-Fujita, M, Loechel, R, Burgess, A C, Miller, D E, Yuzbasiyan-Gurkan, V, Brewer, G J, Glover, T W
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.07.1999
• Subjects: Animals; Base Sequence; Carrier Proteins; Chromosome Mapping - veterinary; Chromosomes, Bacterial; Chromosomes, Human, Pair 2; Copper - metabolism; DNA Primers; Dog Diseases - genetics; Dog Diseases - metabolism; Dogs; Fungal Proteins - genetics; Humans; In Situ Hybridization, Fluorescence; Metabolism, Inborn Errors - genetics; Metabolism, Inborn Errors - metabolism; Metabolism, Inborn Errors - veterinary; Saccharomyces cerevisiae Proteins
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s003359901085

HAH1 (ATOX1) (Klomp et al. 1997), the human ortholog of yeast Atx1p, is a cytoplasmic protein that functions as a copper chaperone and is thought to shuttle copper from the cell membrane to both ATP7B and ATP7A (Pufahl et al. 1997) localized in the trans Golgi complex (Dierick et al. 1997; Payne et al. 1998). While not as strong a candidate as the ATP7B gene, it is possible that a mutation in ATX1 could result in liver cirrhosis via interfering with the normal function of ATP7B without affecting the activity of ATP7A. No mammalian disorders have yet been attributed to a mutation in the ATX1 gene. Yuzbasiyan-Guarkan et al. (1997) performed linkage analysis with several Bedlington terrier pedigrees of the American Kennel Club to identify DNA microsatellite marker C04107 as being tightly linked to the CT locus with a LOD score of 5.96 at recombination fraction of zero. This polymorphic marker has been successfully applied in molecular diagnostic tests for CT in Bedlington terriers (Holmes et al. 1998; Ubbink et al. 1998). In an earlier study (Yuzbasiyan-Gurkan et al. 1993), the CT locus was found to be unlinked to the esterase D (ESD) and retinoblastoma (Rb1) loci, both of which show strong linkage to Wilson disease in humans. This suggested that the CT and ATP7B loci were different and unliked in the dog, but data on linkage of the canine ATP7B, Rb1, and ESD loci is lacking and could differ from that seen in the human genome. In the present study, fluorescent in situ hybridization (FISH) was performed to determine whether candidate genes ATP7B or ATX1 mapped to the same or to different chromosomal locations from C04107. If either ATP7B or ATX1 mapped to the same chromosomal locus as C04107, it would suggest that CT may be a result of a mutation in that gene. If they mapped to different chromosomes, this would strongly support the hypothesis that another gene involved in mammalian copper transport or homeostasis is responsible for canine CT.