OMIA:002608-9615 : Modifier of copper toxicosis, ATP7A-related in Canis lupus familiaris (dog)

Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 300011 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2016

Cross-species summary: Excessive copper deposition in the body due to variants in the ATP7B gene has been named Wilson disease (see OMIA:001071 : Wilson disease). Genetic modifiers have been reported to partly protect against copper accumulation in animals with Wilson disease.

Mapping: Guevara-Fujita et al (1996) mapped the canine ATP7A gene to the X chromosome.

Molecular basis: Fieten et al. (2016): "the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation" Haywood et al. (2023) “Liver and DNA samples from 24 COMMD1 affected and 10 unaffected Bedlingtons were assessed for copper and genetic variants.” The authors tested for variants in COMMD1 (OMIA variant ID:643), ATP7B (OMIA variant ID:106), ATP7A (OMIA variant ID:107) and 2 SNPs in ABCA12 (Haywood et al., 2016). "All dogs only carried the ATP7A:c.980C allele and were therefore negative for the protective mutation."

Breed: Labrador Retriever (Dog) (VBO_0200800).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ATP7A ATPase, Cu++ transporting, alpha polypeptide Canis lupus familiaris X NC_051843.1 (61442067..61595242) ATP7A Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
107 Labrador Retriever (Dog) Modifier of copper toxicosis ATP7A missense Naturally occurring variant CanFam3.1 X g.60279238C>T c.980C>T p.(T327I) rs852523339 2016 26747866 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The phenotype was renamed from 'Menkes disease' to 'Modifier of copper toxicosis' based on feedback from Tom Nagels [10/01/2023].

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002608-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Mutton, J., Yeomans, S., White, J. :
Copper hepatopathies in Australian dogs. Aust Vet J , 2024. Pubmed reference: 38682427. DOI: 10.1111/avj.13338.
2023 Haywood, S., Swinburne, J., Schofield, E., Constantino-Casas, F., Watson, P. :
Copper toxicosis in Bedlington terriers is associated with multiple independent genetic variants. Vet Rec :e2832, 2023. Pubmed reference: 37038639. DOI: 10.1002/vetr.2832.
2022 Takanosu, M., Suzuki, K. :
Genotype frequency of ATP7A and ATP7B mutation-related copper-associated hepatitis in a Japanese guide dog Labrador retriever population. J Vet Med Sci 84:16-19, 2022. Pubmed reference: 34819411. DOI: 10.1292/jvms.21-0369.
2021 Corbee, R.J., Penning, L.C. :
COMMD1 exemplifies the power of inbred dogs to dissect genetic causes of rare copper-related disorders. Animals (Basel) 11:601, 2021. Pubmed reference: 33668783. DOI: 10.3390/ani11030601.
2020 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. Pubmed reference: 33142854. DOI: 10.3390/life10110266.
2019 Pindar, S., Ramirez, C. :
Predicting copper toxicosis: relationship between the ATP7A and ATP7B gene mutations and hepatic copper quantification in dogs. Hum Genet 138:541-546, 2019. Pubmed reference: 31062085. DOI: 10.1007/s00439-019-02010-y.
2016 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. :
The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders. Dis Model Mech 9:25-38, 2016. Pubmed reference: 26747866. DOI: 10.1242/dmm.020263.
1996 Guevara-Fujita, M.L., Loechel, R., Venta, P.J., Yuzbasiyan-Gurkan, V., Brewer, G.J. :
Chromosomal assignment of seven genes on canine chromosomes by fluorescence in situ hybridization Mammalian Genome 7:268-270, 1996. Pubmed reference: 8661696.

Edit History


  • Created by Imke Tammen2 on 10 Jan 2023
  • Changed by Imke Tammen2 on 10 Jan 2023
  • Changed by Imke Tammen2 on 23 Apr 2023