UC Davis Veterinary Genetics Laboratory (VGL) Researchers Identify New Genetic Region Linked to Insidious Uveitis, A Blinding Eye Disease in Appaloosa Horses

A new collaborative study led by Dr. Rebecca Bellone, Director of the UC Davis VGL and a leading expert in equine genomics, has identified a second genetic region associated with insidious uveitis in Appaloosa horses.  

Being part of the research team investigating the genetics of ERU has been deeply rewarding, first as a graduate student, and now as a veterinary student. This disease blinds so many horses, and knowing that my work contributes to understanding its genetic roots is what drives me to keep going.” —Dr. Nicole Kingsley, first author of the study and former Ph.D. student at the UC Davis Veterinary Genetics Laboratory. 

Insidious uveitis is a form of equine recurrent uveitis (ERU)—the leading cause of blindness in horses—that is particularly difficult to detect early due to its initial low-grade inflammation and lack of outward painful signs. The disease is progressive, however, and due to persistent inflammation it causes damage to the eye and can eventually lead to loss of vision. 

Appaloosa horses, known for their distinctive spotted coats, are disproportionately affected by insidious uveitis compared to other breeds. Previous research has linked the leopard complex allele that causes the breed defining spotting pattern (LP) to increased risk of insidious uveitis. However, this genetic factor alone does not fully explain the genetic susceptibility for insidious uveitis in the breed.

To explore additional genetic contributors, the research team conducted a genome-wide association study (GWAS) of 96 Appaloosa horses, incorporating the known risk factors as covariates. The analysis revealed a significant association between insidious uveitis and a 9.7 kilobase region on the X chromosome. Follow-up whole genome sequencing and investigation of a larger cohort of 157 horses, including the 96 GWAS horses, did not identify a causal mutation within the region, but the consistent association with three specific markers on the X chromosome suggests the locus merits further investigation. 

Importantly, the authors note that replication in independent populations is needed before these findings can be used in genetic testing and to inform clinical decisions. At this time, testing for the LP locus, is the only recommended genetic test for risk of insidious uveitis in Appaloosas and closely related breeds. Still, identifying additional genetic markers helps guide future research that can contribute to a more refined risk model and management strategies.

The study was supported by the Morris Animal Foundation, the Townsend Equine Health Research Fund, and the UC Davis Center for Equine Health.

The full publication can be found here.