Canine Disease Genetics – Professor Hannes Lohi lecture

Attended the April 14 lecture organised by “Crusaders4Spinone” . Billed as a lecture on epilepsy, it covered much more. I had been keen to listen to this speaker, Professor Hannes Lohi, PhD, of the molecular genetics department Helsinki. This expert has been fortunate to be in the right place at the right time to exploit the rapidly moving world of canine genetics. At the end of the day i suspect the audience felt they had been given a view of the near future and what it could hold for dog breeders.

It quickly became clear that not only is his department stunningly well funded ( 20 highly qualified staff in his area alone) but also the research once completed has quickly been turned into DNA tests and other information for sale to breeders via his company Genoscopes Labs Ltd, trading under the name  ” MyDogDNA”.

<This first draft might not be as well organised as it could be from my notes,  as listening to a quietly spoken Finn in a room full of eager breeders and owners wasnt always too easy. Transcribing the notes I made begins here:>

The University stores 60,000 samples from 300 breeds, to put this into context our Animal Health Trust has around 20,000 and the big USA “competitor” has more. It quickly became clear that the various researchers are as much in a race against each other as they are in a race to bring us solutions, sharing and co operating isn’t as common as many might wish for. There are only 5 or 6 major laboratories researching dog DNA world wide.

The Finns prefer to use blood samples, but advances in saliva swab analysis means they can now do more with these than they once could. Helpful to hear, as our UK Ministry refuses to allow blood exports from canids unless the blood was drawn for another process ( classic example in wolfhounds would be taking a little extra blood at the time of the PSS puppy shunt test).

I don’t think I had realised before this that dogs share 95% of their DNA with humans – this means that the extensive database  and clinician knowledge the Finns share with their medical colleagues can be raided to benefit either “race”. In humans, this can mean researchers can start to work on therapies to improve the lot of sufferers with a range of conditions, once a gene loci is discovered in a dog breed which maps across to people. Another example given of the benefits of DNA research was from cattle, where a 6 year breed programme can now be reduced to one before, for instance, milk yield is improved.

Epi genetics is an increasingly important area. Away from the lecture, a friend described this in a way to remember –  a redhead would be badly affected by sunburn, so would know to keep out of the sun. In all other circumstances their skin works exactly the same as a darker skinned person – it needs an environmental effect to be expressed as a problem for the individual. HD is a condition in dogs where rearing and exercise can affect the X ray score. In other words, often its not as easy as ” finding the gene”.

Most readers will know about SNP chips, a major tool for the researchers, vastly reduced in price from not too many years ago. The team has access to around 172,000 different markers as the dog genome project has already mapped the entirety of dog DNA.More conditions, including behavioural, are being identified as being linked to particular gene loci all the time.

Professor Hannes was careful to say that nothing in genetics is completely black and white. They have discovered that size, as one instance, is affected by at least 650 genes in humans.So far they can explain around half the eventual body size, as long as they are looking across a large population. Some of these genes for greater size are linked to those for predisposition to cancer ( that sounds like wolfhounds again!).

The Victorians created the idea of “closed breed registries”                    ( pedigree dogs) and there can often be 3 or 4 times more difference between the DNA of different breeds than there is across the whole human race. Geneticists like looking at inbred populations when they dig into specific genes, as it makes the locations easier to find. One success cited was the discovery of the gene location for PRA in the Vallhund. It took the researchers just one week – as it was a recessive gene within an inbred population where they had a good idea already where to start. They can find a recessive gene from just ten samples. Conditions which are multifactorial take hundreds of samples from individual dogs.

Professor Hannes said there are almost too many ideas to work on, as information comes forward from a variety of sources. His team are beginning work on developmental defects in newborn puppies. In Finland breeders have around 10,000 litters per year and its common for breeders to report 1-2 early deaths per litter. The lab is currently looking into this, seeking protein coding deficiencies, as this it is hoped will also help with research into stillbirths in humans.

Their success with the Lagotto breed was accompanied by video of affected puppies of this breed. It resembles a human childhood epilepsy, so they are currently working with this discovered DNA in mice to progress their research. Puppies could present with symptoms aged 1 month – 3 months, and although the disease seemed to go away in terms of no further fits , owners reported changed behaviour in this group as they matured ( less concentration, a sort of attention deficit problem). The question would be was this the result of genetic action, or as a result of brain damage from the fits? They plan a follow up study. In the meantime breeders of Lagottos have a DNA test so they can avoid mating carriers together. The chairman of the Swiss club reported that breeders had no new cases for three years as a result of using this.

Epilepsy is common in dogs. It is complex, might be the action of a multiplicity of genes working together. Epilepsy is difficult to recognise. Seizures can be small, as little as a tic or a vagueness for a brief time.  They can come and go. Some resemble ” childhood epilepsy” in children as it will disappear on adulthood. There followed an interesting digression when a member of the audience asked how sure the researchers could be that any sample they obtained of an ” epileptic dog” was as a result of a ” genetically based” condition – as unless the vet has checked first whether the dog had a thyroid problem the latter condition could be the cause. This was where the notes in the form of a full case history from the examining vetineray surgeon needed to accompany the sample going to the researchers in every instance. I’ve discovered recently that thyroid deficiencies can turn up in aged basset fauve de bretagne, so any ” fitting” would need to be checked out in case there was a simple solution.

One of Helsinki University’s recent research projects is around anxiety conditions. The first step is a questionnaire, identifying the anxiety type ( noise, separation anxiety, both, others) which will be followed up by behavioural tests for a group they select to work on, then clinical tests. They already know there is ” high comorbidity” in that fearful dogs studied who are also noise sensitive are a higher percentage when compared to noise anxious non fearful dogs ( a high 78.8%). They are looking into tail chasing  bull terriers. When an EEG is done there is no sign of abnormality, but is the behaviour caused by a compulsion or a focal seizure? They are looking for a candidate gene. In Great Danes they have already identified the locus for social phobia which is sometimes seen in that breed.

The afternoon session then centred on the “private work”, the DNA profiling which the company “MyDogsDNA” is offering world wide. I’d urge you to look at the website for a better idea of the service provided, its very clear and in English. Of course, as they receive more “customers” so the base will increase and the amount of information expand.

This then is the glimpse into the future. Maybe within five more years, maybe ten,  labs will know exactly where to find each of, say, 34 inherited conditions for a particular breed ( using this figure plucked out of the air for convenience). Simplistic example:  breeder obtains the DNA profile of their stud dog and can see that the male carries some diseases or conditions, is clear of others, might be affected for others. ( as a recent study has shown that all humans carry at least two recessives for bad stuff, this shouldn’t surprise us).

The need for testing animals to look for conditions such as PRA or CEA will be removed – you know the dog’s condition on your report. What then? I would suggest you will be sharing the males DNA report with anyone wanting to use him at stud. Its going to be up to the bitch owner to check that the female is neither a carrier nor affected for any defects within the breed held in common between the projected parents. And once these tests are widely available the clued up puppy buyers will start to demand them before purchasing a puppy.

Two fortunate people then won DNA profiles of their own dogs in the raffle. I think the cost is around £130 per dog.

The future is coming and its closer than we think….. advice on best outcrosses using statistics on associated breeds. Information on diseases within any population, and not just diseases but behavioural traits. I’ve only lightly grazed the top of the iceberg, with gratitude to the speaker and the group within Spinones for setting this session up.

 

 

 

One thought on “Canine Disease Genetics – Professor Hannes Lohi lecture”

  1. Thank you so much for writing up your notes for this seminar. I was wishing I could have been in attendance and your insights were very helpful.

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