Help us fight disease and injury in animals

Current canine research at the AHT

We will consider investigating any inherited canine disorder that has a negative impact on the health, well being or quality of life of dogs.  The choice of diseases that we study is largely driven by the dog owners and breeders we talk to and also the clinicians we liaise with.  We cannot successfully investigate any inherited condition without the co-operation and collaboration of the dog owning and breeding community. 

DNA Samples

The process we use to investigate an inherited disease is more or less the same, regardless of the disease, and always starts with sample collection.  To study any disease we require DNA samples from dogs that are affected with the disease (we call these ‘cases’) and also dogs of the same breed that are unaffected (we call these ‘controls’).  We will usually ask for written confirmation that a dog is affected, such as a letter from the dog’s vet or a copy of his/her eye examination report.  For some diseases we will also need confirmation that the controls are truly clear of disease, such as a clear eye examination report, although for some conditions it will be sufficient for the owner to tell us the dog is not affected (e.g. epilepsy).  The number of cases and controls that we need samples from varies between diseases, and depends on several factors such as the mode of inheritance and the number of genes that are likely to be involved, but is usually between 24 and 100. 

Research

We can collect and store DNA samples indefinitely, until we have enough to start the active research.  Once we have samples from enough dogs, we analyse their DNA with about 170,000 different markers located along the DNA, to hopefully identify regions of the DNA that are similar in the cases and different in the controls; such a region is very likely to harbour the causal mutation.  The dog’s genome consists of around two and a half thousand million (2.5 x 109) nucleotides of DNA.  If each nucleotide was 1mm long the canine genome would stretch from Land’s End to John O’Groats and back again.  A mutation that is responsible for an inherited disease can be anywhere in the DNA and can be as small as a single incorrect nucleotide, so pinpointing a disease-associated mutation can be quite a challenge.  Once we have identified a region (called the ‘critical region’) of the DNA that contains a mutation (equivalent to a one or two mile stretch of road on the journey from Land’s End to John O’Groats and back) we ‘zoom in’ on that region and sequence some or all of the DNA within the region, nucleotide by nucleotide, until we identify the mutation that is causing the disease we are investigating.  Once we have identified the mutation and confirmed we have the correct mutation, by analysing the DNA from a large number of cases and controls, we develop a DNA test that is offered to the public by our DNA testing facility.

Funding

Most of our staff in the Canine Genetics team are currently funded by the Kennel Club Genetics Centre at the AHT but we still need to raise funds to pay for the laboratory materials we use during the active research phase of each investigation.  We routinely apply to funding bodies such as the Kennel Club Charitable Trust and the American Kennel Club Canine Health Foundation; in addition much of our funding comes from Breed Clubs and also from generous donations from individuals.

Projects currently ongoing

 

Hereditary Cataract
The Canine Genetics team is currently involved in several projects that aim to identify genetic variants that contribute to the risk of developing Hereditary Cataract (HC) in several breeds.  Using this information, we will develop DNA-based tools that breeders can use to try and lower the incidence of HC in their breeds.

Findings from our initial studies in the Golden Retriever, American Cocker Spaniel, Large Munsterlander, German Pinscher, Icelandic Sheepdog, Alaskan Malamute, Samoyed and Siberian Husky suggest that HC might be a complex disease in these breeds, possibly involving several genes that might act independently or together to influence the development of HC.  Some of these susceptibility loci may be shared across breeds, like the HSF4 insertion mutation, but it is likely that there will be some that are specific to only one or two breeds.

To tease apart the genetics underlying HC for each of the breeds above, and to add to the data that we already have, we will need to collect at least 48 additional dogs affected by HC and 48 older dogs that are clear of cataracts (see below) for each individual breed.

For the Australian Shepherd, we are investigating the possibility that there may be further gene(s), in addition to the HSF4 deletion mutation, that affect risk of HC in this breed.

We will also investigate HC in any other breeds that are thought to have an inherited susceptibility to cataracts and for which we can collect sufficient DNA samples.  In particular we are currently collecting samples for Miniature Schnauzers with Congenital Hereditary Cataract (CHC) or HC, and Irish Red and White Setters with HC.

Our latest progress reports for individual breeds are now available here.  If you would like additional information regarding our HC research please contact Sally Ricketts.

Q. Which dogs can contribute to the AHT’s Hereditary Cataract research?

A. There are two types of dog that are useful to our research:

i) Dogs of any breed that have been diagnosed as AFFECTED with any bilateral cataract.
ii) Dogs of any breed over the age of 6 years that have had a current eye examination by a veterinary ophthalmologist and are CLEAR of cataracts.

NB for Australian Shepherds the age cut-off for CLEAR dogs is 8 years.  We are currently providing a free DNA test to all Australian Shepherds affected by any bilateral cataract and to any clear of cataract that are over 8 years old.

 

Progressive Retinal Atrophy

The Canine Genetics team is involved in projects to study the genetics of Progressive Retinal Atrophy (PRA) in the Golden Retriever, the Tibetan Spaniel, the Lhasa Apso, and the Gordon Setter as well as late-onset PRA in the Irish Setter.

We aim to identify the genetic mutations that are responsible for PRA in these breeds.  We will develop DNA tests that breeders can use to eliminate this debilitating disease from their breeds.

In addition to the breeds listed above we are also investigating the genetics of PRA in any other breeds for which we can collect sufficient DNA samples.  We also collect and store for future use DNA from dogs of any breed affected with PRA.

Q. Which dogs can contribute to the AHT’s PRA research?

A. There are two types of dog that are useful to our research:

i) Dogs of any breed that have been diagnosed as AFFECTED with Progressive Retinal Atrophy.
ii) Dogs of any breed over the age of 8 years (or over the age of 10 years in the case of Gordon Setters and Irish Setters) that have had a current eye examination by a veterinary ophthalmologist and are CLEAR of PRA.

If you would like additional information regarding our PRA research please contact Louise Downs.

 

Sebaceous Adenitis

The Canine Genetics team is currently involved with a project to identify mutations associated with Sebaceous Adenitis with hyperkeratosis (SA), which is a dermatological condition that has been described in several breeds of dog, most commonly in the Standard Poodle.  It is a condition in which the sebaceous glands in the skin become inflamed and are eventually destroyed, leading to hair loss and secondary skin infections, and is a significant health and welfare problem in affected breeds.

In 2008 the Canine Genetics team at the AHT, funded by a grant from the American Kennel Club Canine Health Foundation, and with invaluable support from the Standard Poodle Club UK, conducted a genetic study of SA in the Standard Poodle.  Although the study was carried out successfully, it failed to identify any regions of the genome which were significantly associated with the disease, which suggests that the disease is genetically complex and will require the analysis of additional samples.

We are committed to continuing our study of SA in the Standard Poodle and are continuing to collect and store samples so that we can analyse SA as a complex disease.  Data generated during the previous study will be saved, and added to additional data generated in the subsequent phase of the study.

Click here to read a full report of the work carried out to date.

Q. Which dogs can contribute to the AHT’s SA research?

A. There are two types of dog that are useful to our research:
i) Dogs that have been examined by a veterinary dermatopathologist and found to have the disease.  This must involve the taking of a skin biopsy.
ii) Dogs over the age of 6 years that have been examined by a veterinary dermatopathologist with a skin biopsy and pronounced clear of the disease.
For all our SA samples it is preferable to have copies of the veterinary skin biopsy examination report.

 

Steroid Responsive Meningitis

Although not fully understood, Beagle Pain Syndrome, clinically known as Steroid Responsive Meningitis (SRM), is thought to be an autoimmune condition that can affect any breed of dog.  Given that certain breeds are over represented with SRM there is a possibility of genetic predisposition.

Meningitis is a disease that affects the meninges, or the membranes that cover the central nervous system.  Most of the time it is contracted as the result of a bacterial or viral infection, but with SRM parts of the body will be falsely recognised as foreign and attacked by the immune system.

SRM most commonly develops in Beagles between six and eight months of age, although has been observed as early as ten weeks and up to two years old.  The condition can either be acute or chronic and typical symptoms are fever, intense neck pain, a stiff gait and depression.  Diagnosis can be made through a spinal tap as well as other laboratory tests, X-rays and CT scans.

The disease can be controlled through immunosuppressive steroid medication, which helps relieve the inflammation of the spinal cord.  Therapy usually begins with high doses of steroids, which are then tapered down slowly over time and after a period on a low dose with no problems, steroid therapy can stop completely if advised by your vet.  Some dogs will never need steroid therapy again, while others may need to stay on a low dose for the rest of their lives.

Click here to read a full report of the work carried out to date

Q. Which dogs can contribute to the AHT’s SRM research?
A. There are two types of dog that are useful to our research:
Dogs that have been diagnosed with SRM, with a copy of the clinical diagnosis.
Dogs over the age of 5 years that are free of SRM.

 

Multifocal Retinal Dysplasia

Retinal Dysplasia is the term given to disorderly proliferation and imperfect differentiation of the developing retina.  Under the British Veterinary Association/Kennel Club/International Sheep Dog Society (BVA/KC/ISDS) Eye Scheme, several breeds are certified for multifocal retinal dysplasia (MRD) (American Cocker Spaniel, English Springer Spaniel, Cavalier King Charles Spaniel, Golden Retriever, Labrador Retriever, Hungarian Puli, and Rottweiler). 

The AHT Canine Genetics group is currently investigating the genetics of MRD in the Golden Retriever, a breed in which the condition is inherited as an autosomal recessive condition [1].  The condition is congenital and it is advised that Golden Retriever puppies should be screened at four to six weeks or at 10 to 12 weeks, supplemented by later examinations for breeding dogs.  Early screening is important  because over time degeneration of abnormal neuronal cells in the dysplastic regions may occur and the originally thickened retina becomes thinner, making mildly dysplastic areas very difficult to detect with an ophthalmoscope [2].

1.       Long SE, Crispin SM. Inheritance of multifocal retinal dysplasia in the golden retriever in the UK. Veterinary Record. 1999; 145: 702-704.
2.       Crispin SM, Long SE, Wheeler CA. Incidence and ocular manifestations of multifocal retinal dysplasia in the golden retriever in the UK. Veterinary Record. 1999; 145: 669-672.

Q. Which dogs can contribute to the AHT’s MRD research?
A. There are two types of dog that are useful to our research:
i) Dogs that have been diagnosed by a veterinary ophthalmologist as affected with MRD at a minimum of two separate eye examinations and that have never passed an eye examination with respect to MRD.
ii) Dogs diagnosed as clear of MRD by a veterinary ophthalmologist, as part of a litter screen.

 

Spinocerebellar Ataxia

Spinocerebellar Ataxia (SCA) in the Italian Spinone is an autosomal recessive neurological disease characterised by truncal ataxia, hypermetria or overreaching, particularly in the hind limbs and impaired balance.  The condition was first reported in 1996, and subsequently there have been cases reported in a number of countries including the UK, the US, Italy, Germany and Holland.  Clinical signs start to appear at three months of age and progress to a degree of dysfunction which leads to euthanasia of affected dogs at an average of one year of age.  The nature of the disease is distressing for both owners and affected animals with the severity of the ataxia in the later stages of the disease putting the animal at a great risk of injury.

Working closely with the Italian Spinone Club of Great Britain we initially collected and extracted DNA from 60 Italian Spinone, including 13 SA cases.  We subsequently performed a whole genome scan and identified a small region of the canine genome associated with SA in the Italian Spinone.

Further funding from the Italian Spinone Club of Great Britain and the Kennel Club was obtained to investigate the region thought to contain the mutation, and although the exact causal mutation has not been identified to date, enough information has been generated to launch a predictive linkage-based DNA test which is accurate to greater than 95%.  The research into SA in the Italian Spinone is currently ongoing.

If you have an Italian Spinone showing signs of ataxia, please contact Oliver Forman.

Q. Which dogs can contribute to the AHT’s SCA research?
A. There are two types of dog that are useful to our research:
i) Dogs that have been diagnosed as AFFECTED with SCA by a veterinarian and confirmed by a veterinary neurologist.
ii) Dogs over the age of 1 year that are free of SCA.

 

Epileptoid Cramping

Epileptoid Cramping in the Norwich Terrier is a disease of increased muscle hypertonicity.

Clinical signs of the condition often include stiffening of the hind limbs and arching of the spine resulting in temporary paralysis of the dog, although its severity varies considerably.

The dog will remain conscious throughout the episode and appears alert.  Duration of episodes is variable, although most last between two and five minutes.  Frequency also varies quite dramatically ranging from a few episodes a week to perhaps just one episode in the dog’s lifetime.  The disease is likely to be a complex genetic condition with many genes involved.

With a huge amount of help from Norwich Terrier owners and breeders, we have collected DNA from 53 dogs with Epileptoid Cramping, and now have a total of 260 DNA samples from Norwich Terriers.  Recently we carried out a whole genome scan which produced interesting results which are being followed up by our collaborators on the project, Dr Hannes Lohi’s lab at the University of Helsinki, Finland.  Our latest progress report is available here. 

Epileptoid Cramping is currently being clinically characterised at the AHT by Luisa De Risio in the Department of Neurology.  Luisa has carried out detailed neurological examinations of three Norwich Terriers, which was kindly funded by the Norwich Terrier Club of Great Britain.  In addition, Luisa has developed a detailed questionnaire to help better characterise the condition.

If you have a Norwich Terrier with Epileptoid Cramping and would like to contribute a DNA sample and complete a questionnaire, please contact Oliver Forman.

Q. Which dogs can contribute to the AHT’s Epileptoid Cramping research?
A. There are two types of dog that are useful to our research:
i) Dogs that have been diagnosed as AFFECTED with Epileptoid Cramping by a veterinarian and confirmed by a veterinary neurologist.
ii) Dogs over the age of 6 years that are free of Epileptoid Cramping, and ideally a sibling of an affected individual.

Late Onset Ataxia (LOA) in the Parson Russell Terrier

Late Onset Ataxia (LOA) is an autosomal recessive genetic disorder that causes dogs affected with the condition to have impaired balance and an uncoordinated gait, making them very wobbly on their feet.  Clinical signs usually start at one year of age, with affected dogs initially showing slight changes in gait and balance.  LOA in the Parson Russell Terrier is a progressive condition and affected dogs can become quite severely affected over a period of a few years.

To date we have conducted a whole genome scan using 16 LOA cases and 16 LOA controls.  This study was successful in identifying a small region of the canine genome associated with LOA, which almost certainly contains the causative mutation.

In the next stage of the research we will sequence this small region of DNA to enable identification of the causal mutation, which will allow us to develop a diagnostic DNA test for LOA.  Funds are currently being collected for this stage of the research; please visit http://funds.gofundme.com/3865c to make a donation.

Q. Which dogs can contribute to the AHT’s LOA research?
Dogs that have been diagnosed with LOA, with a copy of the clinical diagnosis and a short video if possible.

Please contact Oliver Forman for further information.

 

Idiopathic Epilepsy

Epilepsy can be simply defined as the tendency to have recurrent seizures and the term ‘Idiopathic Epilepsy’ means that no underlying cause for the seizures can be identified.  Epilepsy is the most prevalent canine neurological disorder, and is consistently identified by breeders as a major cause for concern.  Many different breeds suffer from epilepsy although the age of onset and the type and pattern of seizures can differ between breeds. 

The AHT Canine Genetics team has investigated the genetics of idiopathic epilepsy as part of a large Collaborative Research Project called LUPA and funded by the European Commission under the 7th Research Framework Programme (www.eurolupa.org).  The project aims to investigate a large number of inherited conditions that are shared by both dogs and man and one of the diseases under investigation is epilepsy.  Idiopathic Epilepsy is likely to be genetically complex in most breeds, meaning several genes and/or environmental factors are involved, but the long term aim of the LUPA study is to identify genetic mutations that increase an individual dog’s risk of developing the condition and to offer genetic tests based on those mutations.  Initial results from these studies in the Border Collie indicates that Idiopathic Epilepsy is likely to be a complex genetic condition, and that samples from a larger number of dogs will be required to take these investigations further.  Our latest progress report is available here.

Q. Which dogs can contribute to the AHT’s Idiopathic Epilepsy research?
A. There are two types of dog that are useful to our research:
i) Dogs of any breed AFFECTED with Idiopathic Epilepsy.  Seizures can have many different causes so it is important that affected dogs have a robust diagnosis of Idiopathic Epilepsy and have had as many tests as possible to rule out other causes for their seizures.  Tests will include blood tests and physical and neurological examinations and ideally would also include brain imaging tests including MRI or CT scan and a CSF tap.  There is no definitive test for Idiopathic Epilepsy and a diagnosis is usually made after all possible known causes of seizures have been eliminated.
ii) Dogs over the age of 7 years that have never had a seizure.

FREQUENTLY ASKED QUESTIONS

Below are some questions that will help you to determine whether your dog can contribute to the AHT’s canine inherited disease research and assist with the development of a DNA test in your breed:

Q.        I have a dog affected with an inherited condition that isn’t listed here – can it still contribute to the AHT’s research?
A.       Yes, we are happy to store DNA from any dog of any breed that is affected with a condition that is probably inherited.  We will store such samples for future investigation.

Q.        My dog can help your research – what do I do next?
A.       Request a DNA sampling pack from the AHT by contacting Bryan McLaughlin (bryan.mclaughlin@aht.org.uk).

The pack contains:
Five buccal swabs
Instructions for the successful collection of DNA
A Sample Submission Form for you to sign confirming that the AHT can use your dog’s DNA for genetic research.  This form also contains instructions for your vet if you choose to submit DNA as a blood sample and information about where to send the swabs/blood, pedigree and health information.

Q.        What happens when the research is complete?
A.       Once research into a particular inherited condition is complete, and a DNA test has been developed, we will provide the results of any dogs that contributed to the research, free of charge, to that dog’s owners upon request.  The dogs we use in individual studies varies depending on our inclusion criteria.

Q.        Can I set up a sample archive for my breed?
A.       Whether it’s for a specific genetic condition or to simply archive samples in the event that heritable problems may arise within a breed at a later date, then the AHT is happy to assist breed clubs and owners alike.  Please click here for a link to our documentation concerning the storage of samples for future use and what is required to initiate the investigation into a disease.

Q.        I have submitted samples in the past.  How can I help further?
A.       The AHT always welcomes updated health information about any dogs we have stored DNA from, and particularly when there has been a change in clinical status relating to a heritable condition, such as developing cataracts, epilepsy or some other inherited disorder.  This information can be vitally important to a particular study when our researchers are analysing the DNA of particular dogs.  Equally so, it is important to let us know if a dog is still healthy many years after sample submission, as older clinically clear dogs can be used as study controls.  For health updates please contact Bryan McLaughlin.

Q.        I have submitted a sample from my dog in the past but now I’ve been asked for a repeat sample – why is that?
A.       The techniques we now use for conducting our genetic analyses of a disease, including whole genome scans and follow-up studies require a greater amount of DNA than for our previous methods.  Sometimes the DNA we obtain from cheek swabs can be variable in quantity and quality, and so when we are ready to start a particular study and we have extracted DNA from the samples that we plan to use, we may find that we only have a limited amount available.  (We tend to extract the DNA at the time of study inception for cases and controls in parallel to avoid any bias.)  Alternatively, we may have completed our initial studies and your dog has been of key importance in our findings, so we require additional DNA to include in our follow-up studies.  We never discard any DNA sample, so if you are asked for a repeat sample it is likely that your dog has been selected to be an important part of our study, so it really is crucial to our research if you are able to provide a quick repeat sample if the dog is still available. 

For more general information about genetic research at the AHT or if you have any further questions please contact us.

ACKNOWLEGDEMENTS

We gratefully acknowledge funding from The Kennel Club Charitable Trust, The American Kennel Club Canine Health Foundation, Masterfoods and Petsavers, the Morris Animal Foundation, the Petplan Charitable Trust, The Alice Noakes Memorial Charitable Trust, The Chailey Charitable Settlement, The Tezmae Charitable Trust and the very many Breed Clubs and individual dog owners who have contributed funds and samples from their dogs to our research.