Scientists hope to root out disease in your dog via genetic sequencing
Molly is a 16-month-old black labrador retriever and like so many dogs of her breed, she is exuberant, biddable and anxious to please. She also has a distinct personality, insists her owner Sussi Wiles, from Harefield, Middlesex. “Molly is just a bit cheeky and will do unexpected things. She will jump up at you when you are not expecting it. But she is also good-natured and cheerful and really likes being around people.”
The labrador retriever, of which there are yellow, chocolate and black varieties, is the UK’s most popular pedigree dog. It is estimated there are several hundred thousand living in homes round the country today, a popularity that has much to do with the dog’s innate, endearing good nature. Hence many owners’ fanatical devotion to them. As one website dedicated to the breed puts it: “When God made labrador retrievers, he was showing off.”
Molly is typical in possessing that lovable, affectionate disposition though she is unusual in one intriguing aspect. Information about her life is now being recorded in extraordinary detail in an online project, called Dogslife, which aims to trace the environmental roots of illnesses in the labrador retriever – and a lot more.
According to scientists at Edinburgh University’s Roslin Institute – the research institute where Dolly the Sheep was created and which launched Dogslife four years ago – the project could become the forerunner of many similar schemes. The aim is to trace the environmental roots of disease – viruses, bacteria, poor food or poor exercise regimes – in other pedigree dogs, and possibly other pedigree animals including top farmyard breeds of bulls and sheep, they say.
For good measure, the Roslin team are planning to augment the data they get from Dogslife by exploiting the very latest techniques in DNA analysis to uncover the genetic – as opposed to the lifestyle – roots of labrador disease. The aim is to create the first labrador genome. Hence its title: the Labradome project. And if it works it could become a pioneer for other pedigree animals, both pets and livestock. The labrador retriever is about to play an unexpectedly important role in the nature-nurture debate, it transpires.
“We picked the labrador for the simple reason that it is the most common pedigree dog in the UK,” says Professor David Hume, Roslin’s director. “However, the lessons learned from it will go far beyond this breed or indeed for dogs in general.
“The key point is that dogs like the labrador retriever are now getting human-like conditions because – as veterinary care and nutrition improves – they are living to ripe old ages when they start to succumb to heart disease, arthritis and cognitive loss. They get Alzheimer’s disease, in effect. They also get obese and suffer diabetes as a consequence. Hence our interest.”
Molly’s involvement in Dogslife requires Wiles to key in reams of information every month about her dog’s diet, hours of exercise, treatments for fleas and worms and any bouts of illness she might suffer. The project – which remains an exclusively labrador project for the moment – currently has more than 4,500 dogs signed up to its website.
Owners put up photos of their pets and regularly input veterinary information – though a select few have even more onerous work to do. They have to send regular samples of their dogs’ excrement to the Roslin team to provide information about the microbes that inhabit the animals’ guts and which might leave them susceptible to various digestive disorders.
From the huge stores of doggy data that are being built up this way, researchers expect they will soon begin to tease out some of the causes of disease that affect labradors in later life and answer key questions about their lifestyles. Are particular types of dog food associated with particular diseases? Do infections at certain stages in a dog’s life leave it vulnerable to more serious diseases in later years? And what exercise regimes are most likely to produce good health in later age for the labrador?
“If a dog is getting the trots all the time, we want to know if it’s because they have got a certain type of organism in their guts,” adds Hume. “And does it make a difference what kind of feed they get: dried food or fresh meat? How does diet affect an animal’s health status?”
Many of the roots of labrador ailments are not going to be environmental in origin, of course, but will be inherited. Hence the Roslin team’s decision to launch the Labradome project in parallel with Dogslife. This will involve geneticists creating a high-quality sequence of the genome of a single labrador retriever: the first time that a full genome of this breed will have been sequenced.
“We are going to sequence in depth the entire complement of genes in a healthy labrador retriever to ensure we have a perfect, accurate picture of the basic genetic structure of one of these dogs,” says Dylan Clements, the Roslin researcher who is leading the project. “Then we will sequence the genomes of a number of other labradors, animals that have various different labrador diseases, such as hip dysplasia.
“Then by comparing their genomes with those of our standard, healthy dog, we will be able to work out what are the differences in genetic sequences between the various animals. In this way, we hope to be able to unravel the genetic roots of some of the labrador retriever’s main illnesses.”
A key factor in setting up the Labradome project has been the recent, dramatic cut in the cost of sequencing genomes. The first human genome that was sequenced just over a decade ago cost billions of pounds. The development of ultra-fast, automated sequencing machines has since slashed the price of unrolling the billions of bases of DNA that make up genomes of mammals. As a result, it should be possible to get a really high-quality genome for a labrador for only a few thousand pounds, says Clements.
Hence the decision to set up the Labradome project on the back of Dogslife, says Hume, and to exploit two of the most dramatic technological marvels of the 21st century: the internet and the genome sequencer. “We are funded to fully sequence 50 labradors which we are choosing from a spectrum of different animals with different phenotypes (observable characteristics) so we can get insights into the causes of the main illnesses that affect the breed.”
One of the principal ailments to be analysed as part of the Labradome project will be a condition called accessory pathway disease, in which the heart short-circuits and beats faster and faster and which can lead to heart failure. Another is called portosystemic shunts, which occurs when a dog’s blood circulation misses out its liver so that it becomes clogged with unhealthy chemicals that would normally be filtered out.
And then there is hip dysplasia, in which the bones that fit into a dog’s hip socket become loose so that the animal develops severe osteoarthritis. “We know this condition is caused by a group of genes, not a singe one, and that is probably true for accessory pathway disease and portosystemic shunts as well. However, if we can create the incredibly detailed sequence that we are planning to do for the labrador retriever and compare dogs with hip dysplasia with our standard healthy animal, we hope we will be able to pin down those genes.”
Armed with this information, researchers can then study how these genes are activated and think of lifestyle changes that might prevent these illnesses from erupting. The point, they say, is that once the Labradome project is finished, it will be possible to look at a top breeding male and see what recessive traits he possesses. Chromosomes come in pairs and if a dog has a gene involved in a disease on one chromosome but has a healthy one on the other chromosome of that pair, it will not be affected by the disease. However, the dog can still pass the disease gene on to future generations so that if two carriers are bred, they can produce offspring affected by the disease. Such conditions are said to be recessive.
“And that is why the Labradome project will be so useful,” says Hume. “We will be able to spot if a stud male has got an unhealthy recessive gene. Then we could breed future generations from it by taking offspring that did not have the chromosome with the disease gene. We would only use offspring that had inherited the chromosome with the healthy gene. Effectively we will be removing that disease from the pedigree. This is known as molecular selection and we are going to use to improve the genetic fitness of the labrador retriever.”
This point is backed by Clements. “This is a fantastically exciting time for canine genetics,” he says. “It has become an amazingly powerful tool to dissect the molecular basis for why these diseases develop and to help us ways to breed out complex inherited diseases.”
For her part, Wiles is simply content that the labrador retriever is getting its proper share of the limelight. “These dogs are incomparable and it seems really fitting that they are leading the way in this sort of research. I know why Molly is fantastic. Now scientists are going to know why that is.”
[“Dog Labrador Nature Of Water” on Shutterstock]