Recently 2 H&W members attended DNA Seminar the Animal Health Trust on behalf of the Heath & Welfare Commitee. Although it was primarily aimed at another breeds eye condition the DNA talk was very interesting.
There was an opportunity to speak to Catherine Mellersh who along with another organisation actually found the marker for this condition. On speaking to her they were directed to Bryan Mclaughlin who heads up the research department at the AHT.
An opportunity to speak to him arose about where we would start as a breed to get the ball rolling in trying to find a marker in our breed for Epilepsy. He informed us that it is not breed specific, & although many breeds do suffer, each breed will have its own marker for the condition, which means if they find a marker for epilepsy in one breed, its not going to necessarily be the same in St Bernards, however there may be some similarities. It is also worth noting that the causes of seizures/epilepsy are not always necessarily genetic. There are many other factors that can cause them such as environmental, diet, illness etc so it is not an easy task to find a marker, but every sample will help.
Bryan is kindly going to send some information & a large box of swabs to help us start to get a DNA bank together at the AHT which they can use in their research to try & find the mutation. He will need information on each dog such as general health, any ailments/conditions
It was suprising to find out that they have no DNA samples for St Bernards held at the AHT for anything at all, so lets hope we can change that & make a change for our breed.
Obviously there may be people a bit worried about giving DNA samples etc, but the AHT do not divulge any information what so ever about the samples they hold to anyone other than the dogs owner whether a problem is found or not.
All information given is confidential.
I hope that we as a breed can help the AHT with their research for this condition & we as a breed can move forward.
If anyone needs more information, please do not hesitate to contact any of the H&W commitee or Bryan Mclaughlin at the AHT.
Bryan can be emailed at the AHT here: Bryan Mclaughlin
Below is some information sent to us by Bryan on how the DNA Samples are stored, & their research purposes, along with some information on epilepsy
Scientists and clinicians at the Animal Health Trust (www.aht.org.uk) are embarking on an exciting project to investigate the genetic basis of epilepsy in the Dog. By combining the expertise of the clinicians to diagnose dogs with idiopathic epilepsy and state of the art genetic research capability we hope to identify the genetic factors involved. If the research is successful the end product will be a DNA test that can identify the risk of developing the condition and passing it on to future generations.
At the moment we are in the initial stages and the project is likely to take several years to complete but the first, and arguably most important, step is DNA sample collection. Once sufficient samples have been collected we will analyse genetic markers distributed evenly across the dogs genome to identify those that are shared by all affected dogs and different from those carried by dogs that don’t suffer from epilepsy. These markers will point us to the region(s) of the DNA that contains mutation(s) that are responsible for causing epilepsy. Once we have determined the region of DNA that contains the mutations we can undertake additional experiments to identify the mutations themselves.
If we are to be successful we need DNA samples from dogs affected with idiopathic epilepsy and their close relatives, and also from unaffected dogs. The DNA can be provided as a blood sample (if blood is being drawn from your dog for another purpose) or as a simple cheek swab. We would also appreciate a pedigree of all dogs that donate a sample so we can understand how the samples we collect are related to one another. This will help us to understand the mode of inheritance of the condition and how many genes are involved.
All research is undertaken in complete confidence. The identity of all samples submitted to the research effort will be kept confidential and the results from individual dogs will only be shared with the dog’s owner(s), once the research has been completed.
We are collecting DNA samples from dogs that are:
(i) Affected with idiopathic epilepsy
(ii) Closely related to a dog that is affected with idiopathic epilepsy
(iii) Unaffected with epilepsy and over 7 years of age
If you have a dog or dogs that meet any of the above criteria then we would very much appreciate a sample from them. To request a free swab kit or sample submission form please contact our sample manager, Bryan McLaughlin (email@example.com) indicating the number of kits you require and your full postal address.
You will need to complete the sample submission form that is included in the swab kit and if your dog is affected please provide us with as much information about your dog’s epilepsy as you can.
It helps us to know:
(i) The age at which your dog developed epilepsy
(ii) How often he / she has a seizure
(iii) How long the seizures last
(iV) What tests or scans you dog has had to determine or rule out possible causes of the epilepsy
I would like to take this opportunity to thank you for your interest in this project, and if you have any more questions please do not hesitate to get in touch.
Cathryn Mellersh, PhD
Department of Genetics
Centre of Preventive Medicine
An increasing number of breed clubs are establishing DNA banks, or archives, to store DNA from dogs that are alive today for the benefit of the breed in the future. The Canine Genetics group at the Animal Health Trust is able to offer DNA Archiving facilities; enquiries should be made by a breed club representative to firstname.lastname@example.org. This article answers frequently asked questions about what a DNA archive is, what the benefits are and what information needs to accompany each DNA sample for the archive to be of maximum benefit.
What is a DNA Archive?
A DNA archive, otherwise known as a DNA bank, is a collection of DNA samples from different individuals that are to be stored to an indefinite period of time. The DNA is collected with a view to using it for future research purposes, as and when it is needed. More information about what the DNA can be used for is included below in ‘What can the stored DNA be used for?’
Which dogs should have their DNA stored?
DNA from any dogs can be stored, but it is especially useful to store DNA from dogs that have or are likely to be bred from and dogs that are known to be closely related to dogs that are affected with inherited conditions.
What can the stored DNA be used for?
The stored DNA can be used for a variety of purposes. One important use for the DNA is to identify mutations responsible for inherited diseases; these diseases can be ones that are known about today or ones that might arise in the future. During a research project where a causal mutation is being sought it is often useful to analyse the DNA from affected dogs and from their parents and grandparents. For late onset conditions parents and grandparents may no longer be alive by the time an affected dog is identified, but if the DNA from those dogs had been stored then it will be available to use long after the dogs have passed away. The AHT has developed at least one DNA test that was made possible by the analysis of DNA from dogs that had been stored for almost 10 years.
Stored DNA can also be used for general breeds studies, such as estimating the genetic diversity of the breed or the frequency of disease mutations in the general population.
How can the DNA be collected?
Ideally the DNA would be collected as a blood sample (~5mls) preserved in EDTA. However, in the
Alternatively the DNA can be collected using buccal (cheek) swabs. Providing the instructions are closely adhered to it is usual to collect enough high-quality DNA for most research purposes.
What information needs to accompany each DNA sample?
The more information that accompanies each DNA sample the more useful it is likely to be. A DNA sample from a dog for which there is little information is unlikely to be of much use. It is usual to provide details such as the dog’s name, breed, KC registration number, D.O.B., coat colour. You will also be asked for a copy of the dog’s 5-generation pedigree and for any information about the health of the dog. Keeping the archive updated with any significant health changes is VERY IMPORTANT. For example, if we want to use a particular dog’s DNA sample to study a specific inherited condition we need to know the dogs’ clinical status with regard to that disease – in other words, we need to know if the dog is affected or unaffected or unknown. If a dog whose DNA is stored unfortunately develops any serious health condition it is very important that the owner informs the AHT so the dog’s record is updated. Likewise, if the dog enjoys a healthy happy life and lives to be a ripe old age that is important information too! You do not need to submit a new DNA sample when you update the archive.
Both dog and owner information is kept in the strictest confidence, although the AHT might, periodically, distribute a list of the names of dogs whose DNA is stored to breed club representatives, for the purposes of sample monitoring. Only the names of dogs will be distributed and no other information will be included.
What does it cost to store DNA?
This varies. If the DNA is to be stored for research into a particular inherited condition, or for any other purposes for which funding has already been obtained, then the DNA can currently be stored free of charge. If the DNA is to be stored for unspecified, future purposes then the AHT asks for a donation of £5 per sample to help cover administrative costs. Details of how to submit a sample can be obtained by emailing email@example.com. This is also the email to use to inform the AHT about a change in your dog’s health.
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. DNA can be collected using buccal (cheek) swabs, which is non-invasive to the dog and simple and convenient for the owner to obtain. Providing the instructions are followed it is usual to collect enough high-quality DNA for most research purposes via this collection method. Ideally the DNA would be collected by a vet as a blood sample, up to 5mls preserved in EDTA. However, Home Office regulations restrict the drawing of blood for non-diagnostic reasons, and if solely intended for research has to be performed under very specific license. Although if a dog is having blood drawn for a veterinary procedure then a vet is permitted to draw a little extra for research purposes.
Follow Up Information
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 researcher’s are analysing this particular individuals DNA among others. 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 to can be used as study controls. Typically there would be a desired lower limit on the age for best use as a control, but this will vary depending on the condition being studied. For new sample submissions or health updates please feel free to get in touch with Bryan McLaughlin (firstname.lastname@example.org)
Once a clinical problem within a breed has been identified as hereditary, and the mode of inheritance has been more or less established, then we can begin to formulate a project plan as to how many samples would be needed and how to use them. For a simple single gene recessive condition we would require at least 12 affected dogs (cases) and the same number of unaffected dogs (controls). If the condition were dominant or a more complex polygenic multifactorial one, then the number of affected and unaffected cases needed would considerably increase to a minimum between 24 and 36 of each.
After each individual DNA extraction has been obtained in sufficient quantities and quality, then a typical course of action would involve running a Whole Genome Scan (WGS). This compares the DNA from cases with the DNA from controls at currently around 170,000 different positions in the genome, in an attempt to find regions that are consistently similar in all the cases and different in the controls. Such regions are highly likely to contain mutations associated with the case condition in question. Once these regions of the genome are identified, additional experiments will be necessary to pinpoint the precise causal mutation, but finding an associated region is a very important initial step on the way to the development of a DNA test.
Canine genetic research staff here at the trust are currently generously supported by the Kennel Club, as part of the Kennel Club Genetics Centre at the Animal Health Trust, but resources such as consumables and laboratory materials are being funded solely by donations from funding organisations, breed clubs and individuals.
The swab kits we issue are free of charge. Although for sample collections that don’t already have funding in place, such as breed DNA archiving, then we do ask that a donation of some kind is made to the charitable trust. Some breed clubs in the past have chosen to purchase a piece of needed laboratory equipment or a freezer to contain their samples, but most common however is a £5 donation per swab kit issued which helps to cover our costs.
The initial WGS analysis is the most expensive overall outlay on consumables, and it currently costs approximately £200 to analyse the DNA from a single dog. There is a minimum order run of 48 samples, therefore to maximise cost efficiency we can perform WGS’s for several studied conditions in conjunction. Additional costs would ultimately depend on the samples, and how the study would proceed after analysing the data obtained by a WGS.