DNA Tests - page 1

[Atopic Dermattis] [CMO - Craniomandibular Osteopathy]
[Cryptorchisism] [Epilespy
[GCL - Globoid Cell Leukodystropy] [Heart Disease
[Hernia] [Luxated Patella] [Pigmentary Glaucoma
[Portal Systemic Shunt
[PRA - Progressive Retinal Atropthy
[vWD - von Willebrands Disease]

Compiled by Jerrie E. Wolfe jerrie@rose-croft.dk 

Genetic or hereditary diseases are conditions caused by subtle damage to the DNA, which is then passed from one generation to the next. The damaged gene is inherited according to the rules of genetics, although the pattern of inheritance may not be obvious without detailed scientific study. The majority of genetic disorders afflicting pedigree dogs show a recessive pattern of inheritance. In these conditions, two copies of the damaged gene, one inherited from the sire and the other from the dam, must be present for an individual to suffer from the disease. Carriers, which have only one copy of the damaged gene, will show no symptoms but can transmit the gene to successive generations. On average, when two such carriers are mated, 25% of the offspring will be affected with the disease - but another 50% will be carriers able to pass the disease on!

In some instances we are not really dealing with a disease, but a defect; such as malocclusions (poor tooth alignment), coloration, etc., things a dog can live with that do not effect it's health. Though important in maintaining the breed within the standard set by the parent clubs and these should not be dismissed, they should be kept in perspective of the severity of other genetic disease and defects; those that cause sever health problems and even death.

DNA tests examine directly the genetic code of the damaged gene and can clearly differentiate normal, affected and carrier individuals. The information in the DNA does not change during the course of a dog's lifetime, so the tests, which require only a small sample of blood or a swab of cheek cells, can be done on a puppy. DNA tests detecting disease mutations are now available for a number of conditions including, globoid cell leukodystrophy in Cairns & Westies, copper toxicosis in Bedlington Terriers, vonWillebrands disease in Scottish Terriers, progressive retinal atrophy (PRA) in Irish Setters and fucosidosis in English Springer Spaniels.

Research groups around the world are busy searching for mutations causing a number of other important hereditary diseases. Most conditions are breed specific; similar diseases in other breeds are not necessarily caused by the same mutation in the same gene. For example, in the case of PRA the disease in Irish Setters is unique to that breed and is a different condition from PRA in the Tibetan Terrier or in the Miniature Longhaired Dachshund. One of the few exceptions is PRA in Labradors (GPRA) and Miniature Poodles which appear to be genetically similar.

Finding the one gene causing a particular disease could be an intimidating task. However, there are several ways to narrow down the search. Research groups, are developing resources for canine genetics which will be useful in directing research towards the most likely genes for a given disease. The objective is to create a genetic map enabling them to concentrate the search for a disease gene to a particular segment of DNA. When complete, the map will consist of 250-300 anonymous DNA markers called microsatellites. Researchers anticipate that such a low-resolution map will be complete sometime next year. How will this help in the search? By comparing the inheritance patterns of each of the microsatellite markers with that of the disease, then they can identify the whereabouts of the disease gene on the DNA without knowing anything else about the gene.

Immediately they have reduced the search to about 0.3% of the total DNA containing only some 150 of the 50,000 genes estimated to be in the dog. At this stage, the DNA microsatellite marker itself can provide a useful guide to whe

ther a dog is a carrier, particularly if other members of the family can be tested too. DNA testing for copper toxicosis in Bedlington Terriers is currently based on such a marker - the disease gene itself has yet to be identified for this condition. Once a DNA microsatellite marker for a disease has been found, then researchers can concentrate on identifying the mutated gene itself. To further reduce the number of candidate genes they can use their knowledge of the clinical symptoms. For example, if a disease affects the eye, we know that the gene involved has to be active in the eye. The list of mutations known to cause genetic diseases in man is growing all the time and can provide a guide to possible mutation sites in simular canine disorders. For instance retinal degeneration in man has been shown to be caused by 12 different genes. By putting together all this information, we can home in on the most likely candidate genes and scan those for the mutation causing the disorder.

 To set up a genetic study to track down a disease gene using DNA markers, researchers n

eed blood samples from families with both clinically normal and clinically affected dogs. They need a minimum of 50 to 60 samples but the more samples they have to test, the more precise the analysis.

Dr. Nigel Holmes in his research for Tibetan Terrier PRA, has used computer simulations to confirm that he now has a large enough number of samples, and is beginning to screen them with the DNA microsatellite markers currently available. There is no way to predict which DNA microsatellite marker will be useful for a particular disease, it may be the first to be tried or it may only be found after several hundred markers have been tested. Once we have a complete genetic map, however, we can be sure that there is a marker within that set that is in the vicinity of the disease gene that we are looking for, and can carry out the search in a more methodical way.

For analysis to be successful all the information on dogs which have been sampled must be 100% accurate; it only needs for one dog to be misdiagnosed to produce a false result from the genetic analysis. To ensure that this does not happen, researchers routinely establish criteria for the various conditions that they study to make sure that they can have total confidence in the diagnoses. Because the symptoms of progressive retinal atrophy become apparent at an early age and because the clinical signs are unambiguous, the assignment of disease status to family members for this disorder has not been a problem.

Lens luxation, however, is less straightforward. Perhaps ironically, it is the assignment of normal status, rather than affected status, that gives us problems in primary lens luxation. Although the first clinical signs can appear early, at 2 years or so, in some individuals the signs may appear as late as 8 years of age. The primary lesion is in a ligament attaching the eye lens, but the problem may only be noticed after the lens has shifted position. To ensure that none of the dogs identified to us as being clinically normal are in fact undiagnosed affected, we are now examining the information provided by breeders for each normal dog to confirm that they have all been diagnosed by a veterinary ophthalmology specialist after reaching the age of 9.

The development of canine genetics is at a very exciting stage. Over the next few years, the mutations underlying a number of important hereditary disorders will be identified and DNA tests devised. As our knowledge of canine genetics increases, progress in studying genetic diseases will accelerate. The availability of widespread  DNA testing will give breeders the information to eliminate disease genes from their stock, whilst retaining genetic characteristics valuable to the breed.

With DNA testing, carriers can be used with confidence since normal offspring can readily be identified.

At the top of this page and on the following page is a short list of the genetics concerns in the Cairn Terrier. This is a list of descriptions of the illnesses and is not given as medical advice. If you have further question please contact your veterinarian and refer to the list of resources listed at the end of the next page.

In 1989 the Cairn Terrier Club of America completed a health survey. A new survey is to be done in 1998. With more research this list will most likely change the incidences of the diseases and may even add a few more anomalies.


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This page was last  March 30, 2002

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