Epilepsy gene identified in dogs

By Jonathan Amos BBC News science reporter

Scientists have identified a faulty gene that causes epilepsy in dogs.

The finding has allowed the researchers to develop a test that could soon help owners breed out the disease.

But the discovery should also aid the quest to understand the more severe human form of the condition, Lafora disease, and other similar afflictions.

The latest development, reported in Science magazine, is an example of how the human and dog genome projects are expected to benefit both species.

Researchers are comparing and contrasting the "life codes" of the two mammals with other animals to track down the genetic causes of ill-health.

Light starter

The study in Science was produced by a Canadian/UK team led from the Hospital for Sick Children (HSC) in Toronto.

The researchers showed that the jerky behaviour and seizures suffered by purebred miniature wirehaired dachshunds were caused by a form of epilepsy called EPM2.
The affected dogs all share a mutation in their EPM2b gene involving multiple repeats in the DNA code that prevent the proper production of protein.

It is thought 5% of miniature wirehaireds in the UK have the disease and perhaps as many as 25% may be carriers of the faulty gene.

Owners usually start to notice a problem with their pets when they are about six years old. Although incurable, the disease can be managed with a controlled diet and drugs.

"These animals will jerk in response to quite specific things, such as sudden movement in their visual field," said Science co-author Clare Rusbridge, a veterinary neurologist at the Stone Lion Veterinary Centre in London.

"They also do it when there is flickering light - this is one of the photosensitive epilepsies. One of the simplest managements is doggy sunglasses, which means they can be walked and enjoy life," she told the BBC News website.

Relentless progression

If dogs can cope with EPM2, the same cannot be said of humans suffering with Lafora disease.

It is the most severe form of teenage-onset epilepsy. It gets progressively worse and usually results in death within a few years of the diagnosis.
"In terms of frequency, it is very rare but it is a horrible disease," said colleague Dr Berge Minassian, whose research group at the HSC has now identified two faulty genes associated with Lafora's.

"The seizures get more and more frequent and severe, and within a year or two they are totally uncontrollable by any means."

For dogs the benefits are more obvious. With a new test for the faulty EPM2b gene, breed clubs could soon start a programme of controlled mating to eradicate the disease in miniature wirehaireds and other breeds, such as basset hounds, in which it has become amplified.

This approach is already being used in Irish setters, for example, to tackle a blinding condition known as progressive retinal atrophy (PRA), and an immune disorder called canine leukocyte adhesion deficiency (Clad).

Just like EPM2, both are the result of recessive mutations - a dog must have two copies (one from each parent) of a "bad" gene to show the disease.

Familiar patterns

The UK Kennel Club is about to stop registering any Irish setter unless it is clear of Clad.

"Because purebred dogs are highly selected - breeders choose the dams and sires they put together - we can impose restrictions to select against dogs that are likely to pass these genes on to future generations," commented Dr Jeff Sampson, the Kennel Club's canine genetics co-ordinator.
There is great hope that purebred dogs, with their large litters and long pedigrees, will offer science the opportunity to rapidly locate faulty genes that in humans would be far more difficult to find because few family members may be alive to study their DNA.

"Human clinicians are increasingly turning to purebred canine populations because these will have similar, if not identical, diseases to us and the clinicians will identify the gene in the dog and that will then give them a handle to start looking in human populations," explained Dr Sampson.

The Toronto hospital research group is already searching for other instances in which the particular pattern of expanded DNA repeats seen in the dachshunds may be driving ill-health.

"We've gone on to check the human genome as well as the genomes of cattle and other species and have found a number of genes that contain such repeats, and we are in the process of figuring out if they are associated with diseases," said Dr Minassian.


The double-stranded DNA molecule is held together by four chemical components, or bases
Adenine (A) bonds with thymine (T); cytosine (C) bonds with guanine (G)
Groupings of these letters form the "code of life"; there are estimated to be about 2.4 billion base pairs in the dog genome wound into 40 distinct bundles, or chromosomes
Written in the DNA are possibly 25,000 genes which dog cells use as starting templates to make proteins; these sophisticated molecules build and maintain the animal's body