Copper Toxicosis in Labradors: A Comprehensive Study

Copper toxicosis in Labradors is a serious condition that affects the liver and can be fatal if left untreated. The condition is caused by a genetic mutation that affects the dog's ability to properly process copper.

Labradors with copper toxicosis often exhibit symptoms such as lethargy, vomiting, and diarrhea. These symptoms can be easily mistaken for other common canine illnesses, making it essential to have your dog regularly tested for copper levels.

The genetic mutation responsible for copper toxicosis in Labradors is inherited in an autosomal recessive pattern. This means that a dog must inherit two copies of the mutated gene, one from each parent, to develop the condition.

Copper toxicosis in Labradors can be caused by a genetic mutation that affects the dog's ability to break down copper in the liver.

This mutation leads to a buildup of copper in the liver, which can cause damage and lead to liver disease.

Labradors with copper toxicosis may also have a higher concentration of copper in their liver than normal Labradors.

Copper levels in the liver are often measured to diagnose copper toxicosis in Labradors.

A liver biopsy is usually needed to confirm the diagnosis of copper toxicosis.

The liver biopsy involves taking a small sample of liver tissue for examination under a microscope.

The results of the liver biopsy will show the extent of liver damage caused by the buildup of copper.

The biopsy results will also help determine the severity of the condition and the best course of treatment.

The research on copper toxicosis in Labradors is ongoing, with a recent article highlighting the importance of continued study on this topic.

Researchers are using various methods to understand the causes and effects of copper toxicosis, including the role of the ATP7A gene, which was previously thought to play a significant role in reducing risk.

A veterinarian suggested that if a dog has two high ALT numbers in a row, a biopsy should be done to diagnose liver issues.

By studying the experiences of dog owners, researchers can gain a better understanding of how to prevent and treat copper toxicosis.

Here are some environmental items that may impact copper levels in dogs:

These items can be avoided or minimized to reduce the risk of copper toxicosis in Labradors.

Next Generation Sequencing is a powerful tool for identifying genetic variants. A total of 59 variants were identified in addition to the previously identified variants in ATP7A and ATP7B.

The sequencing process was highly successful, with a call rate of >80% and median coverage of 69x. Seven genes were not reliably covered, but variants identified in these genes were still included in the statistical analysis.

The sample which was included twice in the NGS showed 99% consistent genotyping results for the identified variants. Genotypes found for the ATP7B:c.4373G>A and ATP7A:980C>T mutations were respectively 96% and 97% consistent with earlier obtained genotyping results.

A total of 44 variants in 25 genes remained after excluding variants with a call rate <50% and a minor allele frequency (MAF) <3%. Two variants were indels, and the other variants were substitutions.

The sequencing process was validated using Sanger DNA sequencing and Kompetitive Allelic Specific PCR (KASP). Genotypes found through KASP and Sanger DNA sequencing were consistent with the NGS results.

We selected 74 genes that potentially play a role in copper toxicosis disease modification through a literature review.

These genes were chosen based on their known role in copper homeostasis, as well as closely related genes or those described with a potential role in copper metabolism or the etiology of copper metabolism disorders.

The full family of COMMD genes was also included, as well as genes involved in the copper metabolism of the mitochondrion and genes involved in the integration of copper in the mitochondrial respiratory chain.

ATP7A and ATP7B genes, previously studied in Labrador Retrievers, were included for quality control purposes to compare genotypes of ATP7A:980C>T and ATP7B:c.4358G>A previously obtained through KASP with the results of the NGS.

An overview of the included genes can be found in Table S2.

The researchers used R version 4.0.2 for all analyses. They analyzed genotype data using the brms package, which performs Bayesian estimation using the Stan programming language.

A specific ordinal regression model with a cumulative link function (probit) was used to assess the association between copper score and a specific variant. This model was used with and without sex, ATP7A, and ATP7B genotype as covariables.

The underlying variable for the copper score was assumed to be continuous in relation to hepatic copper levels. Age of the dog at biopsy could be a confounder, so the necessity to include this factor into the model was assessed.

A univariate analysis using a Spearman's rank correlation analysis was performed to assess the relationship between age of the dog at biopsy and the copper score. This analysis was done using all 239 dogs included in the study.

The researchers also performed a Spearman's rank correlation analysis to assess the relation between quantitative copper levels and the copper score. However, two animals had a copper score of 5, so these were recoded as levels 4 before analysis to avoid problematic small group sizes.

Intriguing read: Why Do Labradors Shed so Much

Genotypes were modeled additively, and the X-chromosomal ATP7A variant was scored as 0 (CY) or 2 (TY) for hemizygous dogs. The results of the models were presented as estimates with 95% credibility intervals on the probit scale.

A variant was assessed as significantly associated with hepatic copper levels if the credibility interval of the full model analysis did not contain 0. The statistical analysis for the variants genotyped in the replication cohort was identical to the NGS cohort.

To evaluate if there were any significant differences between the baseline characteristics of the two cohorts, Pearson's Chi-squared test was used for the non-reference allele frequencies of ATP7A and ATP7B genotypes and female to male ratio.

In this section, we'll take a closer look at the figures that support our research. Boxplots of copper score associations were used to compare different genotypes in the NGS and replication datasets.

These boxplots show the distribution of copper scores across various genotypes, providing a visual representation of the data. A total of 5 genotypes were compared in the NGS dataset.

The boxplots revealed significant differences in copper scores between certain genotypes, indicating a possible genetic influence on copper regulation.

Labradors are one of the breeds most commonly affected by copper toxicosis (CT). Patty Brooks notes that there's continued research on this topic, which is great news for Lab owners.

Chris Lang is new to the topic of CT, and he's wondering if liver disease is the result of CT. He's right to be curious, as Lila Dann shares her personal experience with copper storage issues in her Kees dog, who unfortunately passed away due to liver damage.

Lila Dann also mentions that her dogs were fed the same diet, but only her Kees developed copper storage issues. This highlights the importance of monitoring your dog's diet and health closely.

Feeding your dog a low-copper food can help prevent copper toxicosis. Lila Dann makes sure to feed her dogs the lowest copper food she can find and watches their ALT (alanine transaminase) levels closely.

A biospy is the only way to diagnose liver issues, according to Lila Dann's internal medicine veterinarian. If your dog has two high ALT numbers in a row, it's a good idea to have a biospy done.

Here's a list of environmental items that can impact your dog's copper levels:

Sharlene Pitman notes that the article suggests the ATP7A gene plays a lesser role in reducing risk than originally thought.