The Paw Print Genetics Blog

Picking the Right Genetic Test for Canine Progressive Retinal Atrophy

Picking the Right Genetic Test for Canine Progressive Retinal Atrophy

Canine progressive retinal atrophy (PRA) is a group of inherited eye diseases which are among the most common causes of inherited blindness in domestic dogs. Extensive study and characterization of the various PRAs have led to the discovery of well over a dozen different genetic mutations in many different genes which can now be identified to help prevent, predict, or diagnose PRA in many breeds. However, complicated PRA naming schemes and the breed-specific nature of the PRA tests can make it challenging for dog breeders or veterinarians to select the correct test for the dog in front of them.  

Multiple Genes, Similar Clinical Findings

The known underlying mutations associated with the various forms of PRA are found in a wide variety of different genes. Thus, highlighting the complexity of the biological pathways involved in the development and ongoing maintenance of the eyes. PRAs are marked by the abnormal development and/or the gradual degeneration of rod and cone photoreceptor cells of the retina. Each type of PRA may display variation in the age of onset, speed of disease progression, and the relative rates at which each of the two photoreceptor types are destroyed. However, when it comes to clinical eye examinations, the various forms of PRA are nearly indistinguishable as they share common ophthalmologic clinical signs including progressive decrease in retinal blood vessel size, thinning of the retina, increased light reflection (“eye shine”) off of the structure behind the retina known as the tapetum lucidum, and progressive vision loss. However, these clinical signs only become apparent on eye exam as the dog approaches the typical age of onset for a specific type of PRA.

Despite shared clinical signs, variation in age of onset for the different types of PRA is vast (from the first weeks of life to 15 years old). In part, this variation is determined by the type of cellular dysfunction present. Although there are exceptions, in general, early-onset forms of PRA are often the result of genetic mutations in genes responsible for normal photoreceptor cell development and their names often include the word ‘dystrophy’ to indicate abnormal development (e.g. progressive retinal atrophy, cone-rod dystrophy 1). However, late-onset forms of PRA are generally the result of mutations in genes responsible for the maintenance of mature photoceptor cells and their names often include the word ‘dysplasia’ to indicate degeneration of normally developed cells (e.g. progressive retinal atrophy, rod-cone dysplasia 4). In either case, degeneration of rods and cones, and subsequent blindness, are the unfortunate end points.

Naming Scheme

When it comes to the names associated with the various types of PRA, things get a little tricky. Over the years, the lack of a universally accepted naming scheme for PRA, has led to some confusion among those trying to identify which particular PRA test should be performed for a specific dog.

In general, the PRAs are named for the relative severity of degeneration for each photoreceptor cell type over time. For example, some PRAs have a name that starts with ‘rod-cone’ indicating that the rod photoreceptors are more significantly affected in the early stages of disease. Since rod cells play an important role in low light vision, dogs with primarily rod cell destruction often present with night blindness. In contrast, PRA names starting with ‘cone-rod’ tend to result in preferential destruction of cone photoreceptor cells in early stages of disease. Since cone cells are important for vison in moderate to bright light, dogs with primarily cone cell destruction often present with normal night vision, but impaired vision in brighter environments. However, for most types of PRA, in the end both types of photoreceptor cells are eventually affected, leading to blindness.

Inheritance and Healthy Breeding

Since there are not any commercially-available treatments for PRA currently available, preventing PRA through the genetic testing of breeding dogs and the implementation of informed selective breeding practices remain the best options to prevent PRA-associated blindness. However, the specific inheritance type of a particular PRA may change the way genetic testing results are used to alter breeding practices.

  • Autosomal Recessive- The most common inheritance pattern of the known PRA-associated mutations. Recessive diseases are those that require a dog to inherit two copies of the associated genetic mutation (one from each parent) to be affected. Dogs carrying only a single copy of a recessive PRA mutation are considered asymptomatic carriers of the disease but can have diseased puppies if bred to a dog that has the same mutation. Therefore, simply breeding carriers to dogs which do not have the same mutation as determined through testing (‘clear’ dogs) is a reliable and effective way to prevent affected puppies from being born.
  • Autosomal Dominant- Dominant diseases are those which are expressed in dogs that have inherited only a single copy of the associated genetic mutation from one of its parents. This also means that we would expect one of the parents to also be at-risk or affected with the same disease. One example is the dominant form of PRA seen in mastiffs due to a mutation in the canine RHO gene. Although most mastiff breeders would be unlikely to breed a dog with clinical hereditary blindness, mastiffs which inherit this dominant mutation do not show signs of vision loss until after sexual maturity.  unknowingly produce affected puppies from an affected, yet asymptomatic parent that is not genetically tested. Therefore, it would not be recommended to breed dogs with dominant PRA-associated mutations.
  • X-linked- X-linked diseases are those diseases in which the associated mutation is present on the X chromosome. As a refresher, X-linked diseases are more commonly seen in males because they only need to inherit one copy of the associated mutation to be affected. This is because they do not have a second X chromosome with a normal copy of the gene to compensate for the mutated gene. Females can also be affected by X-linked diseases; however, they must inherit two copies of the associated mutation (one from each parent on their X chromosome) to be affected. Sadly, when dams carry one copy of an X-linked PRA associated mutation, each male puppy has a 50% chance of being affected even though the dams themselves are asymptomatic. Therefore, it would not be recommended to breed female carriers of X-linked PRA.

Picking the Right PRA Test

At Paw Print Genetics (PPG), we have a handy website search tool that allows you to search for disease testing by breed. In breeds with only a single type of PRA test, this tool makes it easy to find the correct test. However, when breeds have multiple types of PRA testing available or when the name of the PRA type you are looking for is similar to another type of PRA, there are a couple of things to keep in mind to make finding the right test easier. First, knowing whether the PRA test you are looking for is of the ‘rod-cone’ or ‘cone-rod’ type can be helpful. For example, at PPG we offer testing for two forms of PRA with very similar names but very different affected breeds: progressive retinal atrophy, cone-rod dystrophy 4 and progressive retinal atrophy, rod-cone dysplasia 4. To make it even trickier, it is a very common practice to write PRA names as acronyms; in this case, ‘PRA-crd4’ and ‘PRA-rcd4’. As you can see, it can be pretty easy to mistake one acronym for the other on a quick glance. However, if you notice which photoreceptor cell is listed first in the name, the inheritance type, the breeds affected, and whether the specific PRA type is considered ‘dystrophy’ (abnormal development) or ‘dysplasia’ (degeneration of normally developed cells), you shouldn’t have too much trouble finding the test you need.

Contact

Paw Print Genetics currently offers testing for a wide variety of inherited canine eye diseases among our list of over 250 genetic tests associated with inherited diseases and traits. In addition to writing the first quality standards and guidelines for canine clinical genetic testing, PPG is widely regarded for exemplary customer care and genetic counseling services. If you have questions about which PRA test to choose or how PPG can assist you in your veterinary practice, please feel free to contact us at AskUs@pawprintgenetics.com or give us a call 509-483-5950 (Mon. to Fri., 8 am to 5 pm Pacific time) to receive a personal consult with one of our veterinarians or geneticists.

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*Photo Credit: Unaltered Photo ‘GSD Gemma’ courtesy of George Agasandian via Flickr Creative Commons license