Researchers have developed a breakthrough genetic test that can eliminate a form of inherited blindness in dogs.

In a study published in the open access journal Genes, researchers from the University of Cambridge identify the genetic mutation that causes progressive retinal atrophies (PRAs) in English Shepherd dogs. In addition to this discovery and due to there currently being no cure for the disease, the team developed a DNA test to identify dogs carrying PRA.

This discovery means that PRA can now be quickly and completely eliminated from the English Shepherd dog population by means of an affordable early-detection DNA test.

As PRA is untreatable, the development of a genetic screening test based on the associated variant marks a significant advancement. It gives dog breeders the opportunity to safeguard the future health of English Shepherd dogs against developing this blinding disease by reducing the frequency of the disease variant within the breed.

What is progressive retinal atrophy (PRA)?

Progressive retinal atrophy (PRA) is a genetically heterogeneous group of hereditary eye diseases affecting a wide range of dog breeds. The disease causes the gradual degeneration of the light-sensitive cells at the back of the eye. Dogs with PRA typically have normal sight at birth. By the age of four or five, they are completely blind. Currently, there is no treatment available for PRA.

“Once the dog’s eyesight starts to fail there’s no treatment – it will end up totally blind.” Dr Katherine Stanbury, author on the paper.

The researchers explain that owners typically do not realise their dog has PRA until it is middle-aged. By this time, the dog may have already bred and passed on the faulty gene to its offspring. Due to the slow progression of the disease, coupled with dogs’ inability to communicate the early signs of sight loss, this has made it difficult to control.

“An owner won’t necessarily notice their dog has got anything wrong with its eyes until it starts bumping into the furniture. Unlike humans who will speak up if their sight isn’t right, dogs just have to get on with things.” – Dr Cathryn Mellersh, author on the paper.

To understand the mechanisms behind this disease the researchers sought to identify the variant associated with PRA in the English Shepherd dog.

Uncovering the genetic mutation responsible for PRA

The researchers collected DNA samples from owners and breeders of English Shepherd dogs. They used two methods to find genes related to inherited diseases in these samples. First, they analysed the samples using whole genome sequencing to read the entire genome. Second, they applied homozygosity mapping to find regions of DNA where both copies (one from each parent) were the same. These methods helped the team pinpoint the genetic mutation responsible for PRA by locating a piece of repetitive short interspersed nuclear element (SINE) DNA inserted within the FAM161A gene.

The genetic mutation identified by the team is recessive, meaning it only causes blindness if a dog inherits two copies of it. If the dog only has one copy, it is a carrier and will not develop PRA but can pass the mutation to its offspring. If two carriers are bred together, about one in four of the puppies will be affected by PRA.

The team found the novel variant associated with PRA in English Shepherd dogs was homozygous in six PRA cases and either heterozygous or absent in control dogs, consistent with a recessive mode of inheritance.

PRA genetic testing

Given the identification of the genetic mutation causing PRA and the fact that the disease is untreatable, the researchers developed a DNA test for English Shepherd dog breeders and owners. The team currently offers a commercial canine genetic testing service providing DNA tests to dog breeders to help them avoid breeding dogs that will develop inherited diseases. Adding to this service, they will now offer a DNA test for PRA in English Shepherd dogs.

The PRA testing kit requires a swab from inside the dog’s mouth, which is then sent to the team for analysis. This service allows breeders and owners to avoid breeding dogs that will develop the inherited disease.

“Now we have a DNA test, there’s no reason why another English Shepherd dog ever needs to be born with this form of progressive retinal atrophy – it gives breeders a way of totally eliminating the disease.” – Dr Stanbury.

Future insights

This discovery marks the thirty-third genetic mutation linked to inherited diseases in dogs identified by the research team, with twenty-three of these causing eye diseases. They note that the health and well-being of many dogs have been compromised due to human breeding practices, leading to the high rates of such diseases.

The development of this DNA test means there is no reason why another English Shepherd dog should be born with PRA. The cost-effective testing kit provides breeders with a simple and affordable way to prevent the disease.

“It’s about prevention, rather than a cure, and it means a huge amount to the people who breed these dogs. They no longer need to worry about whether the puppies are going to be healthy or are going to develop this horrible disease in a few years’ time.” – Dr Mellersh.

The researchers share that their work with dogs could also provide insights into the human version of the disease, retinitis pigmentosa. This could potentially help identify targets for future gene therapy.

Future research

 If you would like to read more research in this area, please see the Genes Special Issue ‘Advances in Canine Genetics’.