Retriever Collapse Mystery Solved

A Mutation in the DNM1 Gene Causes Exercise-Induced Collapse in Labrador Retrievers

by Dr. Barry Starr, Stanford University

A small but increasing number of Labrador retrievers suffer from something called exercise-induced collapse or EIC. Dogs with EIC tend to collapse after 5-20 minutes of vigorous exercise. The dogs usually recover but in rare cases they can actually die.

In a new study, scientists from the University of Minnesota and the University of Saskatchewan have found out why these dogs get this condition. These dogs have a DNA change in both copies of their dynamin 1 (DNM1) gene.

This study not only helps to explain why these dogs collapse, but it will also allow dog breeders to eliminate the DNA change from the retriever breed. It also provides for a genetic test to inform a dog owner whether his or her dog has this DNA difference. If a dog does, then the owner can be sure not to overwork the dog.

Dogs Need Two Copies of the DNA Difference to Get EIC

An example of how carriers
can have a child with a
recessive trait.

Scientists have known about EIC for awhile now. They knew that parent dogs without the disease could still have puppies with EIC. And they knew that if both parent dogs had EIC, then most of their pups would too.

This is the classic pedigree of an autosomal recessive trait. This sounds complicated but is really pretty simple.

Remember, dogs (and lots of other plants and animals including people) have two copies of most of their genes. They get one from their mom and one from their dad. This is true of the gene that is involved in EIC too.

Presumably this gene, like most other genes, comes in more than one version. Most versions do not cause any problems. But at least one can lead to EIC.

Sometimes an animal needs only one copy of a disease version of a gene to end up with the disease. These dominant disease genes are easy to eliminate in a dog population because if the parent has the disease, then they have the gene version. If they aren't allowed to breed, then the disease version will be lost.

But a pup can end up with EIC even if the parent dogs do not have the disease. The most likely explanation for this is that to get EIC, both gene copies need to be the recessive EIC version.

If a dog has only one EIC version of the gene, then they usually won't have EIC. This is because the other copy of the gene can compensate for the disease version. But the dog with just one EIC version of the gene can pass it on to its pups. A dog with a single copy of a recessive gene version is a carrier.

Two EIC carriers each have a 50% chance of passing the EIC gene version to a pup. This pup will then end up with EIC. This is how two parent dogs without EIC can have a pup with the disease.

Before this study, the only way to tell a carrier was if it happened to have pups with another carrier. And a few of those pups happened to end up getting EIC when they grew up.

This is why finding the gene and the EIC gene version is so important. By finding them, scientists will be able to identify carriers and undiagnosed dogs.

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Finding the EIC gene

Finding a gene version responsible for a disease is getting easier but is still not simple. Here is how the researchers went about it in this study.

First they looked at 459 different sections of DNA from 96 dogs from 6 different dog families. They found that the important region was on chromosome 9. They confirmed this by looking at a total of 252 dogs.

Next they looked hard at chromosome 9 in 310 Labrador retrievers, some of which had EIC. At first they couldn't narrow down the region to anything smaller than 4.5 million bases. (A base is a letter of the DNA code.)

This wasn't good enough. It would be too expensive to look at that much DNA. And there are too many differences in that big of a stretch of DNA to easily find the right one.

The researchers noticed that 10% of the EIC dogs had two copies of a smaller section of this DNA. Instead of millions of bases, the researchers were able to narrow it down to around 200,000 bases. An even closer look narrowed the suspected region to 137,000 bases.

The most likely gene in this region to be involved was DNM1. The researchers sequenced this gene and found six differences (or SNPs) in the dogs. Of these, only one, G767T (or R256L), correlated with EIC.

This gene version is surprisingly common in Labrador retrievers (at least in the upper Midwest region of the U.S.). Around 37% of the 400 tested dogs were carriers and 3% had two copies of the G767T (or R256L) gene version.

By finding the gene version responsible for EIC, the researchers have provided the tools for a simple genetic test to identify if a dog is a carrier. Or if a dog has a strong chance to end up with the disease.

This will provide dog owners the tools they need to protect their dogs from EIC. And to provide breeders the information they need to eliminate the gene version from the retriever population. Soon no dog need suffer from this disease ever again. At least until a similar mutation pops up.

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Content provided by the Department of Genetics, Stanford University.