New genetic test for equine uveitis risk

Two genetic markers indicate susceptibility to the vision-threatening inflammatory condition of the eye.

Testing for two specific genetic markers can help identify Appaloosa horses most likely to develop uveitis, according to new research from the University of California, Davis.

All Appaloosa coat patterning, including the leopard pattern, blanket pattern and varnish roan, are produced by the leopard complex spotting gene, referred to as LP. However, to have a specific leopard spotted coat pattern---body-wide, dark, circular, pigmented spots on a white background---a horse needs to have one copy of the LP mutation and have an additional genetic modifier known as PATN1. Previously, research into eye disorders in Appaloosas linked LP to equine recurrent uveitis (ERU), a chronic inflammatory condition that can eventually lead to blindness.

“Based on previous work, we determined that Appaloosas homozygous for the LP allele [meaning they inherit two copies of the gene] are about five to six times more likely to develop ERU than those who are not,” says Rebecca Renee Bellone, PhD. “In our current study, we modeled disease risk based on several parameters and calculated the probability of having disease if we included both LP and PATN1 genotypes in the model. Using 98 animals, we found that the mean probability of getting disease if a horse is homozygous for LP and PATN1 is 90 percent, while the mean probability of disease risk for horses that do not have either LP or PATN1 is 1 percent.”

The research does not establish a causal relationship between LP or PATN1 and uveitis, but simply shows that horses with those alleles are at higher risk for disease, explains Bellone. “Work is ongoing to determine if LP is the causal risk variant or is tagging the causal risk variant,” she says. “In other words, we are still trying to determine if LP is the cause or just being inherited on the same strand of DNA as the cause.”

The current research, however, is sufficient to allow identification through genetic testing of Appaloosas at increased risk of developing uveitis, a proactive step Bellone encourages so owners can be on alert for the disease. “It is recommended that those horses who genotype homozygous for LP (LP/LP) be examined more frequently by a veterinary ophthalmologist for earlier diagnosis and intervention,” she says. “Insidious uveitis, the subclinical manifestation typically seen in Appaloosas, often does not present as outwardly painful episodes and may go unnoticed until there is extensive damage.”

Bellone adds that “trained eyes can sometimes tell the genotype for LP by looking at a horse, but we recommend testing for LP to understand which horses are at highest risk so that they can be carefully monitored by clinicians for signs of ERU or disease progression.”

Finally, Bellone says that despite these findings, she does not advocate testing for these markers to make breeding decisions. “We are not recommending breeding away from LP,” she says. “However, careful considerations should be made concerning producing horses homozygous for LP, as these horses are also night blind and other management considerations are needed for these animals.”

Reference: “Genetic investigation of equine recurrent uveitis in Appaloosa horses,” Animal Genetics, December 2019