Peer-reviewed veterinary case report
Dog gene deletion causes loss of detox enzyme function
By Craft, S et al.·Published in Journal of veterinary internal medicine·2017·Department of Medical Sciences·View original on PubMed →
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Original publication title: A 6-bp Deletion Variant in a Novel Canine Glutathione-S-Transferase Gene (GSTT5) Leads to Loss of Enzyme Function.
- Species:
- dog
Plain-English summary
A study found that a specific genetic change in a new canine gene (GSTT5) leads to a significant reduction in an important enzyme that helps detoxify harmful substances in dogs. This genetic variant was particularly common in beagles and Pembroke Welsh corgis, suggesting these breeds may have a higher risk for certain health issues related to detoxification. The research showed that dogs with this variant had much lower enzyme activity, which could potentially increase their risk for cancer. Further studies are needed to see how widespread this genetic change is among other dog breeds and its implications for their health.
People also search for: dog cancer risk beagle · Pembroke Welsh corgi health issues · dog detoxification enzyme deficiency
Abstract
OBJECTIVES: Glutathione-S-transferases (GSTs) detoxify reactive xenobiotics, and defective GST gene polymorphisms increase cancer risk in humans. A low activity GST-theta variant was previously found in research beagles. The purpose of our study was to determine the molecular basis for this phenotype and its allele frequency in pet dogs. METHODS: Banked livers from 45 dogs of various breeds were screened for low GST-theta activity by the substrate 1,2-dichloro-4-nitrobenzene (DCNB), and were genotyped for variants in a novel canine GST gene, GSTT5. Whole-genome sequences from 266 dogs were genotyped at one discovered variant GSTT5 locus. RESULTS: Canine livers ranged 190-fold in GST-theta activities, and a GSTT5 exon coding variant 385_390delGACCAG (Asp129_Gln130del) was significantly associated with low activity (P < 0.0001) and a marked decrease in hepatic protein expression (P = 0.0026). Recombinant expression of variant GSTT5 led to a 92% decrease in Vfor DCNB (P = 0.0095). The minor allele frequency (MAF) for 385_390delGACCAG was 0.144 in 45 dog livers, but was significantly higher in beagles (0.444) versus nonbeagles (0.007; P = 0.0004). The homozygous genotype was significantly over-represented in Pembroke Welsh corgis (P < 0.0001) based on available whole-genome sequence data. CONCLUSIONS: An Asp129_Gln130del variant in canine GSTT5 is responsible for marked loss of GST-theta enzyme activity. This variant is significantly over-represented in purpose-bred laboratory beagles and in Pembroke Welsh corgis. Additional work will determine the prevalence of this variant among other purebred dogs, and will establish the substrate range of this polymorphic canine enzyme with respect to common environmental carcinogens.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/29105159/