Exploring Genetic Causes of Glaucoma in the American Cocker Spaniel

Glaucoma is a group of eye diseases that damage the optic nerve and ultimately result in irreversible vision loss. Primary angle closure glaucoma (PACG) is the most common form of glaucoma in dogs. It is caused by blockage of the “drain” between the iris (the colored part of the eye) and cornea (the transparent surface of the eye) which allows fluid to build up inside the eyeball. This fluid build-up can cause rapid increases in the pressure within the eyeball (intraocular pressure or IOP) which is painful and requires immediate medical care before it damages the optic nerve.

Several dog breeds, including the American Cocker Spaniel, Basset Hound, Siberian Husky, Poodle, and more are predisposed to PACG, indicating that genetics influence disease development. Sex and age are also predisposing factors, since female and middle-aged to older dogs are more at risk. Previous studies have identified genes that may contribute to glaucoma development in several different breeds, but none have been identified yet in the American Cocker Spaniel. Therefore, a team of AKC Canine Health Foundation (CHF) funded investigators at the University of California, Davis set out to explore the genetic causes of PACG in this breed (CHF Grant 02336: Genetics of Primary Angle Closure Glaucoma in American Cocker Spaniels).

Dr. Thomasy and her team completed a genome-wide association study (GWAS) to compare SNPs (single nucleotide polymorphisms, pronounced “snips”) in the DNA of American Cocker Spaniels with PACG and those that were older and unaffected to look for any genetic regions that are clearly different between the two groups. They identified one region on chromosome 10 that is associated with PACG in this breed. While the difference was not statistically significant, several genes in this region are associated with glaucoma in humans, suggesting that this region may also play a role in canine disease.

Specifically, the majority of American Cocker Spaniels studied with PACG had two copies of the adenine (A) nucleotide at this location on chromosome 10. Having at least one copy of the guanine (G) nucleotide here appeared to reduce the risk of being affected. None of the studied dogs had two copies of guanine. The adenine allele was so common at this location among the dogs studied that it most likely has been inadvertently selected for along with some other trait. For example, selecting for a certain head shape or coat type could have also included this glaucoma risk allele. This conclusion is further supported by the fact that detailed eye examinations showed that all American Cocker Spaniels studied have physical eyeball characteristics that may increase their risk of developing PACG.

Future studies will further explore the region on chromosome 10 identified as relevant to glaucoma development in American Cocker Spaniels and examine how the genetic variations lead to disease. Ultimately, the goal is to develop a genetic test to help breeders choose mating pairs that produce offspring with a decreased risk of developing glaucoma. Understanding the genetic and molecular basis of this disease may help create new testing and treatment strategies for both dogs and humans—helping those at both ends of the leash live longer, healthier lives.