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The Animal Health Trust is to develop a DNA test for Renal Nephropathy in Bull terriers but only if sufficient funding is provided by the breed. It will also need DNA samples from both affected and unaffected dogs.  Clearly we must all work together to make this highly desirable test happen. Here is the latest situation - the letter from Dr Hill has been sent to all the BT club secretaries. The details of DNA sampling and archiving are from the AHT.

Letter to breed club secretaries:

 

Dear Friends,

Towards a DNA test for renal nephropathy in Bull Terriers

In addition to funding, the Animal Health Trust needs DNA samples from up to 50 affected Bull Terriers. This will be a challenge for us to collect as so many owners and breeders are reluctant to believe that their dog is affected, but please be vigilant for affected dogs belonging to your members and provide samples if you possibly can. The AHT will be happy to provide a stock of sampling kits - email Dr Bryan McLaughlin with "Bull Terrier DNA study" as the subject of your email, his address is; bryan.mclaughlin@aht.org.uk  His advice on sampling I am reproducing from an earlier email from him:

"Due to the nature of this disease I realize that sampling is not always easy. May I suggest that if a dog is suspected of the condition, then a sample is taken prior to full diagnosis, and if renal nephropathy is determined post mortem we are informed. Tissue samples may also be taken if at all possible, but these must either be placed in a preservative solution (not formaldehyde) or frozen directly until we can supply the solution."

Dr McLaughlin has also supplied documentation, copied below, to send to the AHT with samples, and a further couple of attachments which may answer your questions. So far as I know only one UK Bull Terrier Club has made a donation to help fund this DNA test. One continental terrier group has promised a donation of £800. Please help us with funding and samples. The Donation web site is  http://www.justgiving.com/Terry-Heath

If you have any questions I will do my best to answer them.

Yours sincerely

Brian

(Dr Brian E Hill, Breed Health Coordinator)

 

Please double click below to download a submission form to be sent with your sample to AHT If this doesn’t work with your browser email Dr Hill at arcanum27@mac.com and ask for a copy to be emailed to you, put “submission form” as the subject.

                                            

 

 

The following two items are useful information from the AHT which may answer some of your questions:

 

Canine DNA storage for future genetic research

 

Sample Collection

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 (bryan.mclaughlin@aht.org.uk)

 

DNA Analysis

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 220,000 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.

 

Funding

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 such as a freezer to store 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.

 

Archiving DNA – Why Do It And What Does It Entail?

 

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 canine.genetics@aht.org.uk.  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 UK, the Home Office has strict regulations restricting the drawing of blood for non-veterinary procedures, so owners should discuss this with their vet before requesting a blood sample solely for the purposes of DNA archiving. If a dog is having blood drawn for a veterinary procedure then a vet is permitted to draw a little bit extra for research purposes (which is how DNA archiving is classified) or to use any residual blood sample that is left over from the veterinary procedure.

 

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 canine.genetics@aht.org.uk.  This is also the email to use to inform the AHT about a change in your dog’s health.

 

                                                                                                                                                                                                                                                                                                          

 

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