Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses.
Abstract: Appaloosa horses are predisposed to equine recurrent uveitis (ERU), an immune-mediated disease characterized by recurring inflammation of the uveal tract in the eye, which is the leading cause of blindness in horses. Nine genetic markers from the ECA1 region responsible for the spotted coat color of Appaloosa horses, and 13 microsatellites spanning the equine major histocompatibility complex (ELA) on ECA20, were evaluated for association with ERU in a group of 53 Appaloosa ERU cases and 43 healthy Appaloosa controls. Three markers were significantly associated (corrected P-value <0.05): a SNP within intron 11 of the TRPM1 gene on ECA1, an ELA class I microsatellite located near the boundary of the ELA class III and class II regions and an ELA class II microsatellite located in intron 1 of the DRA gene. Association between these three genetic markers and the ERU phenotype was confirmed in a second population of 24 insidious ERU Appaloosa cases and 16 Appaloosa controls. The relative odds of being an ERU case for each allele of these three markers were estimated by fitting a logistic mixed model with each of the associated markers independently and with all three markers simultaneously. The risk model using these markers classified ~80% of ERU cases and 75% of controls in the second population as moderate or high risk, and low risk respectively. Future studies to refine the associations at ECA1 and ELA loci and identify functional variants could uncover alleles conferring susceptibility to ERU in Appaloosa horses.
© 2014 Stichting International Foundation for Animal Genetics.
Publication Date: 2014-01-28 PubMed ID: 24467435DOI: 10.1111/age.12129Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research sought to identify the potential genetic markers behind the high prevalence of equine recurrent uveitis (ERU), a leading cause of blindness, amongst Appaloosa horses. It found significant associations with a specific mutation in the TRPM1 gene, and two ELA class microsatellites.
Background and Methodology
- The research focused on the equine recurrent uveitis (ERU), which is an immune-mediated disease causing recurrent inflammation of the uveal tract in a horse’s eye, and is a leading cause of blindness in horses.
- The study was conducted specifically on Appaloosa horses, known for their spotted coats, due to their observed predisposition towards ERU.
- The researchers chose 66 genetic markers that were known to be responsible for the distinct spotted coat color of the Appaloosa horses and were thought to potentially be linked with ERU. These markers consisted of nine from the equine chromosome 1 (ECA1) region and 13 microsatellites from the equine major histocompatibility complex (ELA) on ECA20.
- A group of 53 Appaloosa horses with ERU and a group of 43 healthy Appaloosa horses were studied in order to find potential genetic associations with ERU.
Results
- Three markers – a single nucleotide polymorphism (SNP) within the TRPM1 gene on ECA1, an ELA class I microsatellite located near the boundary of the ELA class III and class II regions, and an ELA class II microsatellite in the DRA gene – displayed significant association with ERU, with an adjusted P-value below 0.05.
- The association between the ERU phenotype and these three markers was confirmed in a secondary population of 24 ERU-affected Appaloosa horses and 16 healthy Appaloosas.
Risk Model Evaluation
- The research estimated the odds of an Appaloosa horse being an ERU case given its alleles for these identified markers.
- A logistic mixed model was fitted to evaluate the relative risk, considering each marker independently and also in combination.
- The risk model managed to classify about 80% of ERU cases and 75% of healthy controls correctly based on these identified apparent genetic risk factors.
Future Research
- The researchers posit that future studies should focus on further refining the associations found on ECA1 and ELA loci and identifying the functional variants.
- Doing such could uncover alleles that make Appaloosa horses susceptible to ERU, aiding the prevention or treatment of the disease in this breed.
Cite This Article
APA
Fritz KL, Kaese HJ, Valberg SJ, Hendrickson JA, Rendahl AK, Bellone RR, Dynes KM, Wagner ML, Lucio MA, Cuomo FM, Brinkmeyer-Langford CL, Skow LC, Mickelson JR, Rutherford MS, McCue ME.
(2014).
Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses.
Anim Genet, 45(3), 392-399.
https://doi.org/10.1111/age.12129 Publication
Researcher Affiliations
- Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55108, USA.
MeSH Terms
- Alleles
- Animals
- Genetic Markers
- Horse Diseases / genetics
- Horses
- Microsatellite Repeats
- Models, Genetic
- Polymorphism, Single Nucleotide
- Risk Factors
- Uveitis / genetics
- Uveitis / veterinary
Grant Funding
- P30 AR057220 / NIAMS NIH HHS
Citations
This article has been cited 17 times.- Kirmse L, Thieme K, Doherr MG, Eule JC. Evaluation of Laboratory Techniques for the Diagnosis of Leptospira-Associated Equine Recurrent Uveitis (ERU) With Focus on the Goldmann-Witmer Coefficient. Vet Ophthalmol 2026 Jan;29(1):e70132.
- Kingsley NB, Sandmeyer L, Dwyer A, Langefeld CD, McMullen RJ Jr, McCue M, Lassaline M, Bellone RR. A genome-wide investigation of insidious uveitis in Appaloosa horses. BMC Genomics 2025 Oct 9;26(1):904.
- Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure. Genes (Basel) 2023 Jul 10;14(7).
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