Scientists have identified a faulty gene that causes epilepsy in dogs.  The researchers have developed a test that could soon help breeders eliminate the disease by imposing restrictions to select against dogs that are likely to pass these genes on to future generations.  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 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 with many other creatures to track down the genetic causes of ill-health. 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 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).
Sequences of these components, called genes, regulate the production of proteins thereby controlling life.  There are estimated to be about two-and-a-half billion base pairs in the dog genome, wound into forty distinct bundles, or chromosomes.  Written in the DNA are possibly 25,000 genes, which dog cells use as templates to make proteins.   These sophisticated molecules build and maintain the animal’s body.

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 five percent of miniature wirehaireds have the disease and perhaps as many as a quarter of them may be carriers of the faulty gene.

Owners usually start to notice a problem with their pets when they are about six years old.  These animals will jerk in response to quite specific things, such as sudden movement in their visual field.   They also do it when there is flickering light – this is one of the photosensitive epilepsies.  One of the simplest management techniques is doggy sunglasses, which enables them to be walked and to enjoy life.  Although incurable, the disease can be managed with a controlled diet and drugs.

Although 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.  The seizures get more and more frequent and severe, and within a year or two they are totally uncontrollable by any means.  In terms of frequency, it is very rare; but it is a horrible disease.  Scientists have recently identified two faulty genes associated with Lafora’s.

For dogs the immediate benefits of this research 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 also become frequent.

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.

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 – they can impose restrictions to select against dogs that are likely to pass these genes on to future generations.

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.

Research group are already searching for other instances in which the particular pattern of expanded DNA repeats seen in the dachshunds may be driving ill-health.  They’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 are in the process of figuring out if they are associated with diseases.