DNA Tests - How to Choose Which Ones to Use
Tufts' Canine and Feline Breeding and Genetics Conference, 2015
Cathryn Mellersh, PhD
Animal Health Trust, Suffolk, UK

 A DNA test gives information about the DNA sequence of an individual dog at a position in the genome that is known to influence a particular inherited trait.

 Most DNA tests are for a specific mutation that has been shown to cause an inherited disorder.

 Sometimes the mutation causes a 'cosmetic' trait, such as coat colour.

 Currently, most DNA tests are for mutations that cause 'Mendelian' or genetically simple inherited disorders.

 Increasingly DNA tests will become available for 'genetic risk factors,' which increase an individual's risk of developing a disorder but are not the 'whole story.'

Inherited disorders can be divided into two broad categories: i) Mendelian or simple disorders, that are caused by single mutations, and ii) complex disorders that are caused by multiple mutations or the interaction between genes and the environment. For simple disorders, which can be recessive or dominant, autosomal or sex-linked, the interpretation of DNA tests is a relatively simple matter, as the result of the genotype predicts very accurately whether the dog will develop the disorder during its lifetime and whether it will pass the disease mutation onto its offspring. Currently, the vast majority of DNA tests available are for genetically simple disorders, but DNA tests based on mutations associated with complex disorders will become increasingly available over coming years.

When considering the use of a particular DNA test, the owner/breeder needs to consider several questions:

1.  Is the DNA test based on good science? Has the mutation been subject to peer-review? It may be wise for owners and breeders to be cautious about using a DNA test that has been available for a while, over 12 months for example, but that has not yet been published in a scientific journal.

2.  Is the mutation associated with disease in your breed? Sometimes clinically similar conditions (progressive retinal atrophy for example) can be caused by different mutations, so it is important to make sure that the DNA test you are considering using is based on a mutation that is relevant to your breed. Most mutations segregate in a single or a small number of breeds only, although there are exceptions, such as the prcd and PLL mutations.

3.  Is information available regarding the disease-associated risk of each genotype? In other words... is it clear that the results mean, in terms of the risk to your dog of developing the disorder and passing it on to any of their offspring? Sometimes a mutation may mean a dog has an increased risk of developing a disease, but if the risk is low then over-enthusiastic elimination of the disease-associated mutation may do more harm than good, in terms of reducing the genetic diversity of a breed without effectively reducing the prevalence of the disorder. If the mutation is described as causal for a disease, that usually means it is the only mutation involved and interpreting the results of a DNA test should be quite straightforward, whereas if a mutation is described as associated with a particular disease it is more likely that the mutation is merely a risk factor for the disease, rather than wholly responsible, and interpretation of the results may be less straightforward.

4.  Is information available regarding the mode of inheritance? Is it clear which matings can and cannot produce dogs that might develop the disorder you are trying to avoid?

5.  Is information available regarding the prevalence of the disorder or the frequency of the mutation in my breed? In other words... do you need to test for this mutation? For some mutations careful studies have been done to estimate how many dogs carry the mutation and this can help a breeder decide whether they need to test for the mutation or not. DNA tests for some mutations have been available for many years and have enabled the effective elimination of the disease mutation from affected breeds.

6.  What are you going to do with the results? How will the results affect my breeding decisions? It is very important that a breeder knows what they will do with the results of a DNA test, in terms of their breeding decisions. It is very important to remember that although breeding individual dogs that are free from disease is paramount, care must also be taken to maintain the genetic diversity of a breed, which means, for example, that breeding with carriers can be advisable.

7.  Has the DNA testing laboratory got a good reputation for accuracy and for a willingness to help resolve queries? Does the lab have ISO accreditation? Was the testing laboratory involved with the research to identify the mutation? This last point can be important because clients may well get better explanations & feedback in the event of queries if the testing laboratory is 'personally' involved with the quest to identify the mutation.

During the presentation all of the above questions will be discussed, and some examples of 'good' and 'not so good' DNA tests will be illustrated. Consideration of the sometimes controversial subject of breeding with carriers will also be covered.


Speaker Information
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Cathryn Mellersh, PhD
Animal Health Trust
Suffolk, UK