Investigation of Genetic Modifiers of Copper Toxicosis in Labrador Retrievers
| Autor: | Wu, Xiaoyan, den Boer, Elise R, Vos-Loohuis, Manon, Monroe, Glen R, Nijman, Isaäc J, van Steenbeek, F.G., Leegwater, Peter A J, Fieten, Hille, Interne geneeskunde GD, dCSCA AVR, dCSCA RMSC-1, CS_Genetics |
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| Přispěvatelé: | Interne geneeskunde GD, dCSCA AVR, dCSCA RMSC-1, CS_Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cirrhosis 040301 veterinary sciences ATP7A Biology Article General Biochemistry Genetics and Molecular Biology RETN 0403 veterinary science Labrador retriever 03 medical and health sciences Internal medicine ATP7B medicine Allele lcsh:Science Ecology Evolution Behavior and Systematics Wilson disease Fatty liver Genetic disorder Paleontology 04 agricultural and veterinary sciences Menkes disease medicine.disease 030104 developmental biology Endocrinology Space and Planetary Science copper dog Labrador Retriever lcsh:Q Resistin copper toxicosis |
| Zdroj: | Life (Basel, Switzerland), 10(11). Multidisciplinary Digital Publishing Institute Life Volume 10 Issue 11 Life, Vol 10, Iss 266, p 266 (2020) |
| ISSN: | 2075-1729 |
| Popis: | Copper toxicosis is a complex genetic disorder in Labrador retrievers characterized by hepatic copper accumulation eventually leading to liver cirrhosis. The variation of hepatic copper levels in Labrador retrievers has been partly explained by mutations in ATP7A c.980C> T and ATP7B c.4358G> A. To further elucidate the genetic background of this disease, we used targeted Next Generation Sequencing (NGS) in a cohort of 95 Labrador retrievers to analyze 72 potential modifier genes for variations associated with hepatic copper levels. Variants associated with copper levels were subsequently evaluated in a replication cohort of 144 Labrador retrievers. A total of 44 variants in 25 different genes were identified, of which four showed significant association with copper levels. Of the four variants found associated with hepatic copper levels in the NGS cohort, one was validated in the replication cohort. The non-reference allele of the variant NC_006602.3.g.52434480C> T in RETN resulting in amino-acid change p.Leu7Phe was associated with decreased hepatic copper levels. In humans, resistin is associated with severity of non-alcoholic fatty liver disease, fibrosis, cirrhosis and mitochondrial dysfunction in hepatocytes. Further studies are needed to investigate the biological function of RETN p.Leu7Phe in the development of copper toxicosis in Labrador retrievers. |
| Databáze: | OpenAIRE |
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