February 15, 2007

Cerebellar Abiotrophy (CA/ataxia) in the Australian Kelpie

by Kathy Gooch

The most prevalent genetic disease to affect the Australian Kelpie is CA (cerebellar abiotrophy). Because the ramifications of this condition are universally widespread it is the most significant genetic disorder in the breed. It is also one which is not openly discussed by breeders. Affected dogs are usually destroyed, with no necropsy being done and the carrier parents are bred to other dogs, only to perpetuate the carrier status. Hopefully this article will answer questions regarding this condition and illustrate the need for a DNA test and co-operation amongst breeders with regards to submitting samples.

What is cerebellar abiotrophy?

The cerebellum is the part of the brain that regulates the control and coordination of movement. In this condition, cells in the cerebellum mature normally before birth, but then deteriorate prematurely causing clinical signs associated with poor coordination and lack of balance. The Purkinje cells in the cerebellum are primarily involved; cells in other areas of the brain may also be affected.

How is cerebellar abiotrophy inherited?

An autosomal recessive mode of inheritance has been confirmed or is strongly suspected for the abiotrophies listed below, with the exception of x-linked cerebellar ataxia in the English pointer, which has an x-linked mode of inheritance. This means BOTH parents must be carriers or affected. Carriers exhibit no symptoms of the disease, while affected dogs can exhibit a range of symptoms from mild to severe.

There seems to be much confusion with regards to how CA is inherited in the Australian Kelpie. Click here for more detailed information.

What breeds are affected by cerebellar abiotrophy?

• Neonatal cerebellar abiotrophy (very rare) - Affected cells start to degenerate before birth, so that signs of cerebellar dysfunction are present at birth or when the pup first walks.
  
  Beagle, Samoyed

• Postnatal cerebellar abiotrophy - Cells in the cerebellum are normal at birth and begin to degenerate at variable times thereafter.
  
  Australian Kelpie, Border Collie, Labrador Retriever - Clinical signs are first seen at 6 to 12 weeks, and the condition worsens quickly (over a few weeks). 

• Cerebellar and extrapyramidal nuclear abiotrophy - Cells in other regions of the brain deteriorate as well.

For many breeds and many disorders, the studies to determine the mode of inheritance or the frequency in the breed have not been carried out, or are inconclusive. We have listed breeds for which there is a consensus among those investigating in this field and among veterinary practitioners, that the condition is significant in this breed.

What does cerebellar abiotrophy mean to your dog & you?

The cerebellum is the part of the brain that regulates the control and coordination of voluntary movement. The clinical signs of cerebellar dysfunction in affected dogs may include poor balance, a wide-based stance (feet planted far apart), stiff or high-stepping gait, apparent lack of awareness of where the feet are (standing or walking with a foot knuckled over), and head or body tremors. These signs worsen either quickly or slowly (see breed list above). Affected dogs may become unable to climb stairs or stand without support. They have normal mental alertness. Clinical signs can come in varying degrees of severity from mildly affected egg; slight head tremor, slight propping in the rear end to falling over and total loss of control. Symptoms usually appear at 6 to 12 weeks. Some dogs adapt to the dysfunction and show little disability.

Where other regions of the brain are also affected, you may see signs such as behaviour change (loss of house training, aggression), confusion, blindness, and seizures.

How is cerebellar abiotrophy diagnosed?

The clinical signs are suggestive of cerebellar disease, particularly if they are seen in a breed in which abiotrophy is known to occur. Your veterinarian will do tests to rule out other conditions that can cause similar signs. Unfortunately 100% diagnoses can only be determined upon necropsy of the brains of suspect animals. This re-enforces the need for a DNA test to determine carrier/affected status.

How is cerebellar abiotrophy treated?

There is no treatment for this condition. Dogs do not recover from this disorder and usually at some point (depending on the rate of the progressive deterioration that occurs), euthanasia becomes the best option.

Breeding advice
Affected dogs, their parents (carriers of the trait), and their siblings (suspect carriers) should NOT be bred. With x-linked cerebellar ataxia, only male pups are affected, and the mother is the carrier of the trait. But this is only in the English Pointer, not the Kelpie.

CA has become a widespread problem in the breed. It is apparent that it is not just an Australian, American, or European problem. Because of the relative ease of importing a dog from Australia, a Rabies free country, it is now a global issue. CA is also in both the Working Kelpie and the Show Kelpie.

More than one Working Kelpie line is affected. Dr. Don Robertson, a West Australian geneticist who studied the problem wrote in an article on CA in Kelpies for the Australian Veterinary Journal in 1989 “In the Kelpies studied here, the putative gene appears to have been inherited from several dogs which have been prominent in sheep dog trials and have been widely used for breeding. Consequently, an increase in the incidence of cerebellar abiotrophy in working sheepdog strains can be expected“. Unfortunately at present there are very few Working Kelpie pedigrees in which these lines do not appear. This once again exemplifies the need for a DNA test.

It seems that the reason it does not appear that CA is a problem in Australia is the “shoot, shovel and shut-up attitude” No one talks about affected litters. They just disappear in a hole. Then the parents which are obviously carriers are bred to other dogs and if nothing shows up the pups are sold as “normal”. The unsuspecting buyer is than buying a possible carrier. Then the buyer purchases another dog from the same lines in the hopes of doing a line breeding. Then as bad luck would have it that dog is a carrier. These dogs are bred and BANG!!!!! You have a litter of affected pups. The ones showing symptoms are shot and the non affected ones sold and bred. Odds are they are carriers as well so the problem continues and continues and continues. Some of these carriers have been exported out of the country only spreading the problem. The issue with CA as well is that it can appear at six weeks as tremors or at two or three years as seizures. This is a terrible loss to many people of a beloved pet, not to mention the time and money put into training a dog.

If a DNA test was developed, affected individuals could be euthanized and carriers could be desexed and still used as working dogs. Also the non carriers of a litter could be bred and the positive traits of those lines still passed on with out the worry of genetic problems. If breeders think that they would lose money as a result of this DNA test, exactly the opposite would occur. If a pup was sold with a CA clear certificate the value of that pup would be greater than those without. Also because of the cost of export, breeders and buyers would be put in a position to have testing done before dogs left the country.

Because the Kelpie has a relatively small gene pool to eliminate excellent carriers from the gene pool would be madness. The KEY is to KNOW THE STATUS of the dogs you are breeding.

The following was published in the recent Working Kelpie Council Newsletter. This is a very positive step forward in the quest for a DNA marker test.

From the WKC NEWS BULLETIN January 2007 No 503

“PROPOSED ATAXIA IN KELPIES RESEARCH PROJECT"

At the WKC October Board meeting It was a the agreed, in principal, that the WKC would help fund a project to develop a "DNA Test" for Ataxia in kelpies under the stewardship of Dr Allan Wilton working at the University of NSW .

In this type of research project the government provides an equal amount of money to the amount supplied by the "industrial partner" (in this case the WKC) provided that the research is approved by the granting body.

The Council has signed an agreement "of support" in an application to Australian Research Council by Dr Wilton. Should the grant be successful the WKC will commit a cash amount per year for 3 years. subject to restrictions placed on the project by the WKC, such as anonymity of breeders (and dog pedigrees) who supply samples for the project . The project, if successful, would get under way in the middle of 2007.

Dr Don Robertson, (our Consulting Geneticist) who has done considerable work on the ataxia problem was asked by the board to consult with Dr Wilton. He reported back at the October meeting which has assisted the board in making the decision.

Printed below are sections of his report to the board meeting which may give readers a greater understanding of research on ataxia

Don Robertson:

" We discovered inherited Ataxia in Kelpies about twenty years ago. We have had a couple of false starts in an attempt to do research with Universities to locate and have a test for the gene. A test for the gene would be terrific. Kathy said in her letters that if we had the DNA test we could breed from dogs that were wonderful sheepdog workers and even if we knew or suspected they were carriers we could breed from them, sort out the pups, identify carriers which we would not breed from unless they were super dogs and we could pursue excellence in working ability without worrying which some breeders do now - "this one is a carrier and that one might also be a carrier and therefore should not make that mating". So it would be good to have a DNA test .Eventually there will be a DNA test because of work being done around the world in laboratories on the dog genome.

I recently heard about Alan Wilton at the University of New South Wales who has being doing research on single gene defects in dogs and has had some success and enjoys a reputation as being good in this field. If the Working Kelpie Council want to pursue Ataxia in Kelpies to try and develop a test I think Alan Wilton working at the University of New South Wales in Sydney near the Working Kelpie Council headquarters would be good choice.

There is no guarantee in doing research it will get the answer for which you hope I have seen farmers in the past who think that because they invested in research that they are entitled to get the answer they paid for. Research doesn't work like that! So it could be that the Working Kelpie Council would invest and yet not get the answer hoped for in the time.

Looking ahead I've got no doubt DNA selection will be the way of the future - cattle, sheep, poultry are all having their genomes described and genotypes identified that are responsible for production. So I think that within some years genes will be identified for heading ability, for bite and non bite - all the things we know are inherited in dogs from observation of sheep dog families. Anticipating that in future, you might see a further justification for the investment in research, in that, the WKC would establish a working relationship with a dog genetics laboratory in Sydney near to WKC headquarters. The WKC would get used to handling DNA data. There will be things that emerge as soon as DNA is collected For example a lot of the pedigrees we have been recording will be proved to be wrong. It's happened in cattle, it's happened in sheep, it's happened in humans. In thoroughbreds the recorders insist on a blood test so they know the parents without doubt. For that reason I think it would be quite sensible for the WKC to be involved in co-ordinating and the collecting the samples and sending out samplers to breeders. WKC gets practice in handling DNA data and accumulates the data.

This also leads to a proviso that if WKC goes ahead with this research project I think you should write into the contract that the DNA collected for Ataxia testing is not to be used for any other purpose without the permission of the Working Kelpie Council"

ANNUAL GENERAL MEETING April 13th 2007.

The AGM will be held on the 13th April and we have invited Dr Alan Wilton to attend and speak to us about the planned research. Please make a real effort to attend.”

As with any genetic problem within a breed, only ethical breeding and testing can stop it. If breeders continue to hide their head in the sand regarding this disease the problem will only become more embedded in the breed and be harder to eradicate.

Because the symptoms of CA are not always definitive and varying degrees occur, this may not be a simple gene. This is what Dr. Wilton will determine. What is needed now is co-operation from all breeders who may have suspect dogs or litters to submit blood to Dr. Wilton. This can be done from overseas as well as Australia. These samples once again do not go through me or the WKC but can be submitted directly to Dr. Wilton. They must be submitted with a pedigree. All information will be retained by Dr. Wilton in confidence.

His contact info is;

Alan Wilton
School of Biotechnology and Biomolecular Sciences
University of New South Wales
NSW  2052  Australia
Phone +61 2 9385 2019
Fax +61 2 9385 1483
Mobile 0422 736 425

Additional information on CA/ataxia can be found at the following sites:

www.wobblyscotties.com