Research on Inherited Diseases in Dogs at the
Jenny Morris


The Animal Health Trust ( is a charity that has been helping dogs, cats and horses for more than half a century. The AHT provides specialist veterinary clinical, diagnostic and surgical services, and is dedicated to the study of diseases in cats, dogs and horses.

Scientists at the AHT are investigating the genetic mutations that cause a variety of inherited conditions in many breeds of dog, with a long term view to increase understanding of the diseases and develop DNA tests for breeders to use to reduce the frequency of the diseases. The Canine Genetics Group is currently investigating a number of inherited eye conditions, including cataracts and progressive retinal atrophies, epilepsy and several other neurological conditions. The Oncology Research Group is studying a number of common cancers developed by dogs, and would like the help of Scottish Terriers owners to collect samples for research into melanoma, a cancer that affects Scottish Terriers.

Canine Genetics Group
The Canine Genetics team ( is leading the assault on canine inherited disease in the UK by undertaking research into a wide variety of inherited diseases. The group works with dog owners and breeders to identify inherited conditions that impose a health and welfare burden on dogs and develop DNA tests and other tools to help eliminate those conditions form breeds at risk. The work relies on the cooperation dog owners and breeders the world over, without whom progress would not be possible.

It is no secret that purebred dogs suffer from more than their fair share of inherited disease. This is due to several factors, including the fact that many breeds originated from small numbers of founders, the fact that the parents of most purebred dogs are more or less related to one another and the popular sire effect.

Some diseases are relatively easy for conscientious breeders to eliminate, particularly those caused by dominant mutations that manifest themselves early in life. Dogs only need inherit one copy of a dominant mutation to be affected, and every dog affected by a dominant condition must have at least one affected parent Recessive conditions are harder to eliminate because dogs carrying a single copy of the causal mutation are healthy but will pass the mutation to half of their offspring; a dog is only affected if it inherits the mutation from both parents. Complex diseases, caused by mutations in multiple genes and/or environmental effects are also very difficult to eliminate.

The only way to guarantee the complete elimination of recessive diseases from purebred dog populations is with the use of DNA testing. DNA tests analyse DNA from individual dogs for the presence or absence of a mutation that research has demonstrated is associated with a particular inherited disease. Once a dog's genotype is known, with regard to the mutation, sensible breeding programmes can minimise the risk of producing affected puppies and allow the mutation to be slowly and safely eliminated from breeds at risk while maintaining maximum genetic diversity. For recessive conditions, careful selection of breeding partners means no dog needs be removed from a breeding programme; carriers and even affected dogs can be safely bred with providing they are only mated to DNA tested, clear dogs. DNA tests can also aid diagnosis of disease, particularly for those diseases which share clinical signs but are caused by different mutations. For these diseases DNA testing can provide the ultimate diagnosis by informing the veterinarian which mutation(s) a dog does or doesn't carry.

The development of a DNA test for any inherited disease always starts as a research project. At the Animal Health Trust a large number of research projects are underway that are aimed at understanding the genetic basis of a wide variety of inherited conditions in many different breeds of dog. Most of these projects have a similar experimental plan; DNA is initially collected from two types of dog -those that are affected with the inherited condition under investigation (these are known as the 'cases') and those that are unaffected (known as 'controls'). Accurately 'phenotyped' samples are essential -in other words it is critical that good clinical information accompanies each DNA sample so the researchers know whether a dog is a case or a control. For late onset conditions controls need to be over the average age of onset, so it is certain that they are truly unaffected by the disease. For some conditions controls can be diagnosed by their owners. Epilepsy is one such example; owners usually know whether their dog has ever had a seizure, whereas for some inherited eye conditions an ophthalmologist's examination is required to determine whether a dog is truly unaffected. Using sophisticated technology the DNA from the two sample sets is compared and regions of the DNA that are shared between affected dogs and different in the unaffected dogs are identified. These 'critical' regions harbour the mutations being sought and their identification is analogous to reducing the search for the proverbial 'needle in a haystack' to a single hay bale within a field of 38 haystacks. Additional experiments follow to progressively reduce and refine the size of the critical region until the causal mutation is identified and a DNA test can be developed.

The ultimate success of each research project depends first and foremost on the availability of DNA samples from affected and unaffected dogs as well as on sufficient funding. At the AHT we collect DNA samples from individually owned, pet dogs living in ordinary people's homes. The DNA is collected as simple cheek swabs that owners can take themselves; it is a painless procedure that most dogs don't object to at all. The timeframe for developing a DNA test varies, but active research cannot begin until sufficient samples have been collected. A minimum of 12 cases and 12 controls need to be collected for recessive conditions, although this should be considered a bare minimum. For dominant and complex conditions upwards of 50 cases and 50 controls may be needed. Once the samples are in hand identifying the causal mutation can take from months to years, but as DNA technology continues to improve and the tools available become increasingly sophisticated the time needed to identify a mutation and develop a DNA test can be expected to decrease.

Oncology Research Group
The Oncology Research Group is collecting samples for a project seeking to identify the inherited genetic mutations responsible for Scottish Terriers having an increased risk of developing melanomas. The project is part of the LUPA project (httQ://, a 4 year initiative involving 20 veterinary schools from 12 European countries.
Melanomas arise from cells (containing the pigment melanin) that occur in the skin ('cutaneous melanoma'), in the mouth ('oral melanoma'), under toe nails ('ungual melanoma'), and in the eye ('ocular/veal melanoma'). The severity of a melanoma depends upon location, with oral tumours being the most likely to spread. Black coated breeds appear to be more susceptible to developing cutaneous melanomas, but Scottish Terriers appear to have an increased risk of developing both oral and cutaneous melanomas.
Through the development of DNA tests, the ability to identify dogs that carry the gene mutations conferring an increased risk will be useful to vets as it will identify dogs that may benefit from careful monitoring for early detection of cancer, and thereby early treatment. The research will also increase understanding of how melanomas develop, ultimately assisting the development of new therapies.
If your Scottish Terrier is suspected as having a melanoma, you can help the research by asking your vet to collect two types of sample:

  1. A surplus blood sample (in an EDTA tube), OR two cheek swabs (these can be collected by you, or your vet, using a cheek swab kit that can be obtained from the AHT)
  2. A small piece (a 3-5mm cube) of the biopsy of the suspected tumour (normally removed for diagnostic histopathology), which can be stored in a freezer, and then sent to the AHT (in a special solvent, called 'QIAzol', provided by the AHT)
To request a cheek swab kit and/or an QIAzol sample tube (for a tumour biopsy), please contact: Lisa Jeffery (Tel: 01638 751000, extension 1214; E-mail:

For more information about the project, please contact: Dr Mike Starkey (Tel: 01638 555603; E-mail:; Website: httQ://