Gene responsible for a form of blindness in dogs identified

Cambridge scientists have identified the genetic mutation that causes progressive retinal atrophy in English Shepherd dogs, a disease which results in incurable blindness as the rods and cones in the eye slowly degrade. The hope is, by identifying the gene responsible, dog breeders will be able to eradicate the condition in the species. Chris Smith interviewed Cambridge’s Cathryn Mellersh, and first, the person responsible for helping the research team a great deal, John Coombs, who owns an English Shepherd dog called Shola…

John - Mountain rescue search dogs are used to locate missing people and are mainly used in the dark and in woodland where visual methods of search don't work and the dog's nose is able to detect people. Shola was trained to do that. She's that good that we decided to have a litter of pups with her, so when I went back to reintroduce her to work with my mountain rescue team, it became evident that she was struggling in the dark. We went to a canine eye specialist and she was diagnosed with PRA

Chris - And Cathryn, what is PRA and how did you become part of this story?

Cathryn - In PRA, which stands for Progressive Retinal Atrophy, the photoreceptors, which are very specialised cells at the back of the eye and that help translate what we see to help our brain understand that as a visual image, in PRA affected dogs these degenerate. They stop working and over time. That means that the affected dog will sadly usually go completely blind.

Chris - These are the rods and cones that people will probably more colloquially know them as. Does the fact John said it manifests in the dark first, is that relevant here?

Cathryn - So the cones work in light situations and help us see colour and visual acuity. So when a human is reading, for example, they're using their cones. When you are in dim light, we use our rods. So the fact that Shola needed to work in low light situations, that was when it was first noticed that her vision was deteriorating, and that was because rods degenerate first. Then, unfortunately, the cones degenerate as well. Then the dog becomes unable to see in light conditions,

Chris - Do we know why this occurs? And therefore what underpinning cause exists for this?

Cathryn - PRA in different breeds is caused by different mutations in different genes. What we do know is that the protein that this gene codes for plays a very important role in the maintenance or the health of photoreceptors. This mutation basically stops that protein working properly.

Chris - And you genetically tested Shola to show that she was actually manifesting one of these gene changes?

Cathryn - We collected DNA from Shola and we actually found five other English Shepherd dogs that were affected with PRA as well. We collected DNA from all of them. We also collected DNA from about 20 English Shepherds whose eyesight was good and we compared the DNA from the affected dogs with the unaffected dogs. We were able to hone in on this mutation. So the dog has about 2.4 billion letters of DNA and we were able to find this mutation, which is actually the insertion of 224 letters of DNA that that shouldn't really be there. So in terms of the whole genome, it's quite a small mistake, but in this case it has quite profound impact on the way that this particular protein functions.

Chris - Is there anything we can do about the condition? Because having detected that this gene change exists in an animal, can we stop or slow down the disease? Can we reverse it or is it irreversible?

Cathryn - So at the moment, it is irreversible, but there's a lot of work going on in human medicine to try and do what is known as gene therapy or gene augmentation where scientists and doctors inject a correct version of this gene into the retina. And because the gene that Shola's mutation is in is shared with humans, it could in time join the collective research that's being done and have a positive impact on our ability to treat this disease in humans at least. I think it's unlikely that we would ever do gene therapy in dogs. It takes a long time to develop and it's very expensive. The real benefit to dogs from this research is we can now screen the DNA of dogs that are going to be bred with and make sure that we don't breed together two dogs that carry the same mutation.

Chris - And John, how's Shola getting on now? Are you compensating for the fact that her sights poor by doing other things in a different way? More things she can smell, more things that she can feel and sense to enable her to maintain her quality of life?

John - Her quality of life, I think it's really good. Dogs, in any case, live in a world of scent and she's able to remember where the obstacles are that she might bump into and seems to have a very happy and relaxed life.