Dogs get the SNIP

Dr Jeff SampsonAn article from the August 2007 edition of the Kennel Gazette written by Dr Jeff Sampson who is the Kennel Club's Canine Genetics Co-ordinator.

The recent publication of the canine genome sequence provides a whole new set of tools that research groups will be able to use to learn more about the genetics of the dog - it has generated in excess of 2,000,000 different Single Nucleotide Polymorphisms, or SNPs (pronounced ‘snips’).  But more of this later…

The last 10 years has certainly seen a huge explosion in our understanding of canine genes, what they are, how they work and the possible consequences if a fault occurs in one of them.  Most of this progress has really piggy-backed on research to discover more about human genes and the part they play in human disease.  In fact, the beginning of our understanding of canine molecular genetics goes back to the late ‘80s/early ‘90s. It was then that research groups began to think about clever ways of identifying the faulty genes that underlie many of the canine diseases that impose a significant disease burden on the dog.

We now know that it takes around 22,000 different genes to make a dog. Back then, estimates were somewhat higher, at around 100,000 genes, and we really knew little about any of them, but what we did know was that each and every gene in the dog would be found on one or other of the dog’s 39 different chromosomes, and that these chromosomes were the vehicles that carried genes from one generation to the other. In the late ‘80s and early ‘90s, canine chromosomes were largely unchartered territory, as indeed were the human chromosomes. However, there was the realisation that progress toward identifying individual genes involved in canine disease would rely solely on generating chromosomal maps that would allow us to navigate the 39 canine chromosomes and know where we were at any particular point, and what genes would be in the vicinity.

So, research in the ‘90s focused nearly exclusively on the generation of these chromosome maps, and a very effective collaboration was established amongst scientists in Europe and America to this end.  The aim was to put easily identifiable ‘markers’ at regular intervals along each and every one of the 39 canine chromosomes, milestones if you like. The markers were, in fact, special sequences of DNA that were to be found at just one location on one chromosome, and nowhere else on any of the other chromosomes. As time passed, the density of markers grew and each six months or so a new, more dense marker map would be published, but the number of markers were still measured in only 1,000s.

These maps have been crucial in the search for individual canine genes and by the end of the ‘90s they were dense enough to allow us to use them to track down individual mutant genes involved in canine inherited disease. The early years of this new century saw these maps being put to very good use by groups interested in identifying the genetic fault underlying their ‘favourite’ inherited disease. Progress has been rapid, so that today we probably understand the genetic cause for around 25 per cent of all known single gene inherited diseases in the dog.  More importantly, we now have simple DNA tests for these conditions and these tests are proving invaluable tools to help breeders select against these mutant genes in their breeding programmes, thereby lowering the prevalence of the disease in the breed.

The Kennel Club Charitable Trust and the Kennel Club have not been slow to realise the true value and potential of this research. Over the last seven or so years the Charitable Trust has donated somewhere in the region of £1 million to research projects designed to better understand the molecular genetics of inherited disease in the dog and develop DNA tests for increasing numbers of these conditions. The Kennel Club has played its part as well, not only by providing funds for the Charitable Trust to hand out, but also by raising breeder awareness of the importance that this new technology has to them and the future health of the dog. The Kennel Club has also introduced Official DNA Testing Schemes for breeds that are provided with a new DNA test for one of its breed-specific diseases. These Schemes not only encourage breeders to use the newly available DNA test, but they also provide Open Registers of dogs that have beeN tested and their DNA test result, an essential facility that will allow breeders to select genetically compatible mates for their dogs.

Scientific progress often goes in incremental jumps, fuelled by a new and highly significant scientific discovery. The whole of molecular biological progress achieved in the last half of the 20th Century was only made possible by Watson’s and Crick’s discovery of the structure of DNA in the early 1950s. The next major discovery for canine genetics came in 2005 with the publication of the entire genome sequence of the dog. This has led to the discovery of a new type of genetic marker to build canine genome maps, the SNP. We now have two million of these SNPs to create new generations of maps for canine chromosomes.  Using the distance analogy, if the old maps had a marker placed at every kilometre, then the new SNP maps have a marker at every metre. This 1,000-fold increase in map density will have a really significant impact on genetic progress. The time taken to identify new single gene mutations will be reduced from months/years to, possibly, weeks. More importantly, these new maps will, for the first time, allow research groups to search for multiple genes involved in polygenic diseases at the same time. DNA tests for conditions like hip dysplasia really are just around the corner.

 

 

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Charitable Trust, Dog Health and DNA 

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