DNA Testing

The Association the Dutch Schapendoes is frequently asked about several available DNA tests at different laboratories. Genetic tests for pets, more and more are launched every day. Hundreds of thousands of pets are tested by their pets, out of love and concern for their pet.

However, many of these tests are breed specific, and are offered for use in all breeds. Many of these tests are based on small studies with limited numeric proof, the correctness is often not validated. There is also no validation that the tests are guaranteed and applicable for all dogbreeds.

Many vets have limited knowlegde about these tests and cannot inform concerned owners. That is natural, a vet is not a genetic expert. But is is therefore of great concern that these tests are so popular in use.

The board and the breeding committee of the VNS agree with the statement of the Scientific Committee of the Nordic Kennel Union (NKU/VK). They issued clear information on DNA testing and we would like to publish their statment:

Information and policy from the Scientific Committee of the Nordic Kennel Union (NKU/VK) regarding the use of genetic tests in dog breeding.

The availability of genetic tests for different diseases in dogs has increased dramatically in recent years. For breeders and dog owners, the utility and accuracy of these tests are often difficult to assess. Even though DNA tests offer new opportunities as a tool for breeding, they also imply new questions and challenges. The fact that a genetic test is available for a disease in a breed does not automatically mean that the test is accurate or appropriate to use as basis for breeding decisions. The Scientific Committee of the Nordic Kennel Union (NKU/VK) would like to stress that genetic testing in dogs should be used with common sense and caution. The following points should serve as guidelines for breeders and dog owners in the Nordic countries regarding the use of genetic tests.

Genetic testing – opportunities and challenges

The sequencing of the dog genome in 2005 marked the start of a rapid development of genetic tests for various conditions in dogs. Today, laboratories worldwide provide DNA testing for numerous diseases as well as colors and some other traits. A genetic test can be performed at any time during the dog’s life, and only needs to be done once as the result will not change over time. Genetic testing for conditions caused by a single mutation, i.e. autosomal recessive diseases, makes it possible to assess if a dog is expected to become clinically affected by a specific disease, before symptoms have appeared. One can also see if the dog carries the disease mutation (i.e. is a heterozygous carrier), and thus is likely to transmit the disease allele to its offspring. This knowledge is particularly important for diseases that are difficult to diagnose, develop late in life and/or are of major clinical importance in the breed(s) concerned.
The availability of genetic tests enables an enhanced selection against various diseases. Thanks to this new technology, individuals that are suspected carriers of disease alleles may be tested and do not have to be excluded from breeding on uncertain grounds. Carriers may even be used for breeding, if mated to a dog free from the disease mutation. Moreover, two carriers will not risk to be accidentally mated, thus avoiding affected offspring. Genetic tests may also help veterinarians to diagnose various diseases.

So far it sounds good. However, there are many aggravating circumstances that call for thoughtfulness, and in some cases skepticism. Not all genetic tests offered can be considered reliable and/or suitable to be implemented in a breeding program. The utilization of a DNA test that is not accurate or applicable in a breed may result in potential breeding animals being excluded inappropriately. Or even worse, a dog may falsely be judged as being free from a disease mutation. There are several potential reasons for a genetic test not being reliable or applicable. The genetic background of the disease may be more complex than is considered or detected by the test (e.g., with additional genes and/or environmental factors involved) which may result in discrepancy between the genotype (test result) and phenotype (the clinical status) of a dog. In addition, the test may be validated for one or a few breeds, but not for others. The test may also be irrelevant in the sense that the disease does not occur, or is very rare, in the breed concerned. Applying a test that is irrelevant or inaccurate may result in focus being taken away from more important issues with respect to health and wellbeing.
NKU/VK would like to emphasize that the importance of a genetic test should be evaluated in relation to other aspects, such as other diseases, included in the breeding goal for a specific breed. Otherwise, there is a risk of too much focus on conditions that are easy to “measure” and record. It is therefore of great significance that the overall breeding strategy of each breed clearly states what priorities should be made in breeding, with respect to all traits included in the breeding goal. The dogs’ overall health status and long-term sustainability with respect to genetic variation are important components in this prioritization.

Not the answer to everything

For many hereditary diseases, the same or similar clinical symptoms may be caused by diverse mutations. In other words, the genetic background to what would normally be considered the same disease may differ. This could occur within a breed or across different breeds. For example, there may be genetic differences between populations of the same breed in different countries.

Molecular genetic studies of various diseases in dogs typically focus on one or a few breeds. When the finding of a mutation is to be implemented to other breeds than those included in the original study, the results are often disappointing. The mutation that causes a particular disease in one breed does not necessarily have the same effect in another breed. For example, the eye disease progressive retinal atrophy (PRA) is a collective term for various forms of atrophy of the retina, caused by diverse mutations. In some breeds, e.g. the Golden Retriever, several forms of PRA are prevalent within the same population. It could be, e.g., that a dog free from one PRA mutation is a carrier of or affected by another form of PRA.

Validation of genetic tests is a complex task. Not only owners and breeders, but also breeding officials and professionals, may have difficulties to find and interpret scientific information needed to assess whether a test can be considered reliable and useful or not. There are currently no regulations to stop laboratories from marketing tests with little or no evidence of efficacy or accuracy. In many cases, more and better information from the suppliers of tests is needed, and should be demanded. Moreover, the international dog community should make additional efforts to support dog breeders and owners in this regard.

NKU/VK would like to stress that a dog showing clinical symptoms of a serious disease should not be used for breeding, regardless of the genetic test result. The dog’s clinical health status is in that sense always superior to the genetic status.
Moreover, NKU/VK sees a need for further efforts from the international dog community to support dog breeders and owners with respect to validation and guidance on the use of genetic tests.

The inheritance may be unclear

Many of the genetic tests offered are for diseases inherited in a simple autosomal recessive way. This means that the disease is caused by a single mutation, that in a homozygous genotype (when inherited from both parents) will cause clinical symptoms of the disease. Genetic tests for autosomal recessive conditions will classify dogs as free, carriers or affected. A dog classified as free did not inherit the disease causing mutation from either parent. Hence, it will not be affected by this particular mutation and there is no risk of passing on the mutation to its offspring. A carrier dog has inherited the mutation from one of its parents, i.e. is heterozygous for the mutation. This dog will not itself be clinically affected but may pass on the mutation to its offspring. A genetically affected dog is homozygous for the mutation and will most likely develop clinical symptoms of the disease over time.

Thanks to DNA tests for autosomal recessive conditions it is possible to use carrier dogs in breeding, provided that they are mated to a dog free from the mutation. This, of course, requires that the test is validated and accurate. To decrease the prevalence of the mutation over time, carrier dogs should be used cautiously in breeding.
Nevertheless, many of the most prevalent diseases in dogs have a more complex genetic background, being influenced by several genes as well as environmental effects. For these diseases the genetic background is not fully understood. Even though one or several mutation(s) with a large effect on a complex disease may be found, there are also other modifying genes and/or environmental factors that influence the phenotype. This makes it more complicated to provide and interpret genetic tests for quantitative diseases.

Where a test exists for a complex trait, the mutation (or mutations) tested for may imply an increased risk for a specific condition; however, it is often unclear how high the risk of clinical disease is. Far from all genetically-affected dogs will develop clinical symptoms. Moreover, the test does not provide information on what other genetic risk factors the dog may carry, or to what extent also environmental factors influence the phenotype.

For some of the genetic tests based on mutations influencing a quantitative disease, or a disease with undefined inheritance, the so-called penetrance is only 2-5%. This implies that a dog with the specific mutation has only a 2-5% risk of showing clinical symptoms of the disease. In some cases, diseases that were initially thought to be inherited in a simple autosomal recessive manner have been shown to have a more complex genetic background. As a breeder or a dog owner it can be difficult to find information on the inheritance of a specific disease or to assess whether a genetic test is sufficiently validated or not. Information on the laboratory webpage may give some guidance. If the inheritance is described as showing incomplete penetrance, or the test result for genetically affected dogs is said to imply an increased risk of disease, caution is indicated and further investigation, before using the test, is recommended.
An obvious risk with genetic tests for diseases where the inheritance is not yet completely understood is that potential breeding animals are excluded based on uncertain grounds, or that the test incorrectly categorizes individuals free from a disease for which they might have other genetic risk factors. Moreover, if the risk allele tested for is frequent in the population the gene pool may be severely limited.
The general approach of NKU/VK is to advice against the use of genetic tests for conditions where the inheritance is unclear. Tests for diseases that are influenced by many genes should be applied only in cases where evidence based on scientific publications has established that the mutation or mutations cause a significant and defined risk of disease, and provided that the condition is of clinical relevance in the breed concerned.

Combination tests for several diseases
A relatively new phenomenon on the DNA testing market is laboratories offering multi or combination tests for a wide variety of mutations. Several genetic tests for various diseases as well as other traits are combined into one test package, and this is offered to breed groups or in some cases to all breeds. Hence, the owner or breeder will get genotype results for their dog for as many as a dozen to over a hundred different mutations.

This may seem like a convenient and cost-efficient way to get the most information about the dog’s genetic makeup. However, the results of these multi-tests are often difficult to interpret and of a limited value, or even misleading, for breeding purposes. It should be emphasized that breeders and owners of stud dogs have to consider the test result in breeding, even if some of the mutations included are not sufficiently validated or of any relevance to the breed concerned. Hence, inaccurate test results or genotype information for irrelevant conditions may imply negative consequences for the gene pool and the development of other traits in the breeding goal. In some breeds, especially numerically small populations, use of these multi-tests risk to pose serious difficulties in finding dogs for mating that match in genotype with respect to all the mutations included.

In light of the above, NKU/VK are reluctant to promote the use of multi-tests and combination test packages currently available. This position is based on the shortcomings in validation and/or relevance for some of the mutations included in these packages, as well as the potential negative consequences on the overall breeding goal that an uncritical use of genetic tests is likely to cause. Instead, NKU/VK recommends breeders and dog owners test for the specific mutation(s) that are relevant in the current breed, provided that these tests are validated.

Moreover, NKU/VK would like to emphasize the importance of breeders and/or dog owners carefully evaluating the usefulness and accuracy of a genetic test before it is performed. Only use tests that are properly evaluated and for conditions that are of clinical relevance in the breed. No dog, or other living creature, is completely free of disease mutations. Uncritical use of DNA tests may in the worst case result in negative effects on the breed’s health and gene pool. Please contact your breed club for more information if you are doubtful.

General policy regarding the application of genetic tests in dog breeding
Based on the information above, the Scientific Committee of the Nordic Kennel Union (NKU/VK) would like to make the following general statement regarding the application of genetic tests in dog breeding:

Genetic testing is an excellent tool in breeding for improved dog health, provided that the tests are reliable, relevant and used wisely. Breeders and dog owners should carefully evaluate the benefits and consequences of a genetic test before it is applied. A one-sided or exaggerated focus on DNA test results may result in an increased risk that other important conditions or characteristics are overlooked. The Scientific Committee of NKU would like to emphasize that the breeding program should be based on the prevalence and severity of various health issues, rather than on the availability of genetic tests. If a disease does not constitute a clinical problem in the breed and/or the DNA test offered is not validated or accurate, it is better to refrain from testing the dog. Otherwise, there is an obvious risk of excluding potential breeding animals, and thus decreasing genetic variation, based on uncertain or false grounds. It is important to keep in mind that dog breeding is about much more than specific diseases and that genetic tests, even though today they are many, do not give the entire picture.

Sofia Malm, on behalf of NKU/VK