FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Anim Genet / Heritability of insidious uveitis in Appaloosa horses.
Animal genetics2022; 53(6); 872-877; doi: 10.1111/age.13267

Heritability of insidious uveitis in Appaloosa horses.

Abstract: Equine recurrent uveitis (ERU) is a blinding ocular disorder among horses, and the Appaloosa horse breed is disproportionally affected by a chronic form of this intraocular inflammatory disease known as insidious uveitis. Strong breed predisposition and previous investigations suggest that there is a genetic component to the pathology of insidious uveitis among Appaloosa horses; however, no estimates of the heritability of the disease have previously been determined. This study aimed to characterize the genetic underpinning of the disease by estimating the heritability for insidious uveitis among Appaloosas. After combining two genotyping array datasets from the Illumina Equine SNP70 BeadChip and the Axiom Equine 670 K Genotyping Array, heritability was estimated for 59 affected and 83 unaffected horses using both restricted maximum likelihood (REML) and phenotype correlation - genotype correlation solvers from the linkage disequilibrium adjusted kinship software. Based on previous research, age and sex were used as covariates, and the locus responsible for the characteristic Appaloosa coat pattern (LP), previously associated with ERU risk, was included as a fixed effect ('top predictor'). Using prevalence values from 0.05 to 0.42, the heritability estimate for insidious uveitis ranged from 0.95 (SE = 0.14) to 1.74 (SE = 0.25) with LP contributing 0.16-0.33 to the estimate. This study suggests that insidious uveitis is highly heritable (REML 95% CI, h2  = 0.68-1.0) and additional loci outside of LP are contributing to the genetic risk for insidious uveitis for Appaloosas. Once identified, these other genetic factors may lead to new disease mitigation efforts in veterinary care and breeding practices.
© 2022 Stichting International Foundation for Animal Genetics.
Get Full Text
Publication Date: 2022-10-09 PubMed ID: 36210489DOI: 10.1111/age.13267Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research work investigates the genetic predisposition of the Appaloosa horse breed to an ocular disorder called insidious uveitis, and illustrates a high heritability of this disease in the breed, suggesting a clear genetic link driving the condition.

Introduction to the Study

  • The research focuses on Equine Recurrent Uveitis (ERU), an ocular disorder causing blindness in horses. A chronic form of this disease, known as insidious uveitis, prominently affects the Appaloosa horse breed.
  • The strong prevalence of insidious uveitis in the Appaloosa breed, along with previous investigations, hinted at a genetic component contributing to the disease’s pathology.
  • However, there weren’t any former estimates concerning the heritability of insidious uveitis among Appaloosa horses which this research aims to uncover.

Methods of the Study

  • The team combined data from two genotyping array datasets – one from the Illumina Equine SNP70 BeadChip and the other from the Axiom Equine 670K Genotyping Array.
  • They estimated the heritability of the disease among 59 affected and 83 unaffected horses with the help of restricted maximum likelihood (REML) and two problem solvers linked to the linkage disequilibrium adjusted kinship software.
  • A covariate is a variable that could potentially influence the research’s outcome. In this case, the researchers used age and sex as covariates to control their potential impact on the heritability estimates. That was based on previous research suggesting these variables’ potential role in the disease’s manifestation.
  • The characteristic Appaloosa coat pattern’s genetic locus (LP), previously linked with ERU risk, was included in the study as a fixed effect or ‘top predictor’.

Results of the Study

  • Depending on varying prevalence values between 0.05 and 0.42, the heritability estimates for insidious uveitis ranged from 0.95 (SE = 0.14) to 1.74 (SE = 0.25).
  • The locus responsible for the Appaloosa breed’s specific coat pattern (LP) was seen to contribute between 0.16-0.33 to these heritability estimates.
  • The research found that insidious uveitis was highly heritable (the REML 95% CI, h ranged between 0.68-1.0).

Conclusion and Future Implications

  • The study concludes that there are additional loci apart from LP, contributing towards the genetic risk for insidious uveitis in Appaloosa horses.
  • Identifying such additional genetic factors could pave the way for new strategies to mitigate the disease, mainly through veterinary care and alterations in breeding practices.

Cite This Article

APA
Kingsley NB, Sandmeyer L, Norton EM, Speed D, Dwyer A, Lassaline M, McCue M, Bellone RR. (2022). Heritability of insidious uveitis in Appaloosa horses. Anim Genet, 53(6), 872-877. https://doi.org/10.1111/age.13267

Publication

Animal genetics
ISSN: 1365-2052
NlmUniqueID: 8605704
Country: England
Language: English
Volume: 53
Issue: 6
Pages: 872-877

Researcher Affiliations

Kingsley, Nicole B
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California - Davis, Davis, California, USA.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, California, USA.
Sandmeyer, Lynne
  • Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Norton, Elaine M
  • School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA.
Speed, Doug
  • Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
Dwyer, Ann
  • Genesee Valley Equine Clinic, LLC, Scottsville, New York, USA.
Lassaline, Mary
  • School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
McCue, Molly
  • Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA.
Bellone, Rebecca R
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California - Davis, Davis, California, USA.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, California, USA.

MeSH Terms

  • Horses / genetics
  • Animals
  • Horse Diseases / genetics
  • Horse Diseases / epidemiology
  • Uveitis / genetics
  • Uveitis / veterinary
  • Genotype
  • Risk Factors

Grant Funding

  • Center for Equine Health
  • D16EQ-028 / Morris Animal Foundation
  • Townsend Equine Health Research Fund (TEHRF)

References

This article includes 31 references
  1. Baumgart A, Gerhards H. Besonderheiten der Tigerschecken-Uveitis und möglicher Cyclosporin A-Einsatz in deren Therapie in Deutschland. Pferdeheilkunde 30(6), 626-632.
  2. Beeson SK, Schaefer RJ, Mason VC, McCue ME. Robust remapping of equine SNP array coordinates to Eq쪳. Animal Genetics 50(1), 114-115.
    doi: 10.1111/age.12745google scholar: lookup
  3. Bellone RR, Brooks SA, Sandmeyer L, Murphy BA, Forsyth G, Archer S. Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the appaloosa horse (Equus caballus). Genetics 179(4), 1861-1870.
    doi: 10.1534/genetics.108.088807google scholar: lookup
  4. Bellone RR, Forsyth G, Leeb T, Archer S, Sigurdsson S, Imsland F. Fine-mapping and mutation analysis of TRPM1: A candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. Briefings in Functional Genomics & Proteomics 9(3), 193-207.
    doi: 10.1093/bfgp/elq002google scholar: lookup
  5. Bellone RR, Holl H, Setaluri V, Devi S, Maddodi N, Archer S. Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PLoS One 8(10), 1-14.
    doi: 10.1371/journal.pone.0078280google scholar: lookup
  6. Bellone RR, Liu J, Petersen JL, Mack M, Singer-Berk M, Drögemüller C. A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses. International Journal of Cancer 141, 342-353.
    doi: 10.1002/ijc.30744google scholar: lookup
  7. Brooks D, Matthews AG. Chapter 5, Equine Ophthalmology. .
  8. Deeg CA. Ocular immunology in equine recurrent uveitis. Veterinary Ophthalmology 11(SUPPL 1), 61-65.
    doi: 10.1111/j.1463-5224.2008.00625.xgoogle scholar: lookup
  9. Dempster E, Lerner I. Heritability of threshold characters. Genetics 35(2), 212-236.
    doi: 10.1093/genetics/35.2.212google scholar: lookup
  10. Dwyer AE, Crockett RS, Kalsow CM. Association of leptospiral seroreactivity and breed with uveitis and blindness in horses: 372 cases (1986-1993). Journal of the American Veterinary Medical Association 207(10), 1327-1331.
  11. Fritz KL, Kaese HJ, Valberg SJ, Hendrickson JA, Rendahl AK, Bellone RR. Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses. Animal Genetics 45(3), 392-399.
    doi: 10.1111/age.12129google scholar: lookup
  12. Gerding JC, Gilger BC. Prognosis and impact of equine recurrent uveitis. Equine Veterinary Journal 48(3), 290-298.
    doi: 10.1111/evj.12451google scholar: lookup
  13. Gilger BC, Deeg CA. Equine recurrent uveitis. pp. 317-349.
  14. Golan D, Lander ES, Rosset S. Measuring missing heritability: Inferring the contribution of common variants. Proceedings of the National Academy of Sciences of the United States of America 111(49), E5272-E5281.
    doi: 10.1073/pnas.1419064111google scholar: lookup
  15. Lee SH, Wray NR, Goddard ME, Visscher PM. Estimating missing heritability for disease from genome-wide association studies. American Journal of Human Genetics 88(3), 294-305.
    doi: 10.1016/j.ajhg.2011.02.002google scholar: lookup
  16. McCoy AM, McCue ME. Validation of imputation between equine genotyping arrays. Animal Genetics 45(1), 153.
    doi: 10.1111/age.12093google scholar: lookup
  17. McCoy AM, Norton EM, Kemper AM, Beeson SK, Mickelson JR, McCue ME. SNP-based heritability and genetic architecture of tarsal osteochondrosis in North American Standardbred horses. Animal Genetics 50(1), 78-81.
    doi: 10.1111/age.12738google scholar: lookup
  18. McMullen RJ, Fischer BM. Medical and surgical management of equine recurrent uveitis. The Veterinary Clinics of North America. Equine Practice 33(3), 465-481.
    doi: 10.1016/j.cveq.2017.07.003google scholar: lookup
  19. Norton E, Schultz N, Geor R, McFarlane D, Mickelson J, McCue M. Genome-wide association analyses of equine metabolic syndrome phenotypes in welsh ponies and morgan horses. Genes (Basel) 10(11), 1-23.
    doi: 10.3390/genes10110893google scholar: lookup
  20. Polle F, Storey E, Eades S, Alt D, Hornsby R, Zuerner R. Role of intraocular leptospira infections in the pathogenesis of equine recurrent uveitis in the southern United States. Journal of Equine Veterinary Science 34(11-12), 1300-1306.
    doi: 10.1016/j.jevs.2014.09.010google scholar: lookup
  21. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D. PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics 81(3), 559-575.
    doi: 10.1086/519795google scholar: lookup
  22. Rockwell H, Mack M, Famula T, Sandmeyer L, Bauer B, Dwyer A. Genetic investigation of equine recurrent uveitis in Appaloosa horses. Animal Genetics 51(1), 111-116.
    doi: 10.1111/age.12883google scholar: lookup
  23. Sandmeyer LS, Bauer BS, Feng CX, Grahn BH. Equine recurrent uveitis in western Canadian prairie provinces: A retrospective study (2002-2015). The Canadian Veterinary Journal 58, 717-722.
  24. Sandmeyer LS, Kingsley NB, Walder C, Archer S, Leis ML, Bellone RR. Risk factors for equine recurrent uveitis in a population of Appaloosa horses in western Canada. Veterinary Ophthalmology 23(3), 515-525.
    doi: 10.1111/vop.12749google scholar: lookup
  25. Schaefer RJ, McCue ME. Equine genotyping arrays. The Veterinary Clinics of North America. Equine Practice 36(2), 183-193.
    doi: 10.1016/j.cveq.2020.03.001google scholar: lookup
  26. Schaefer RJ, Schubert M, Bailey E, Bannasch DL, Barrey E, Bar-Gal GK. Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds. BMC Genomics 18(1), 1-18.
    doi: 10.1186/s12864-017-3943-8google scholar: lookup
  27. Speed D, Hemani G, Johnson MR, Balding DJ. Improved heritability estimation from genome-wide SNPs. American Journal of Human Genetics 91(6), 1011-1021.
    doi: 10.1016/j.ajhg.2012.10.010google scholar: lookup
  28. Speed D, Cai N, Johnson MR, Nejentsev S, Balding DJ. Reevaluation of SNP heritability in complex human traits. Nature Genetics 49(7), 986-992.
    doi: 10.1038/ng.3865google scholar: lookup
  29. Weale ME. Quality control for genome-wide association studies. .
    doi: 10.1007/978-1-60327-367-1_19google scholar: lookup
  30. Weissbrod O, Flint J, Rosset S. Estimating SNP-based heritability and genetic correlation in case-control studies directly and with summary statistics. American Journal of Human Genetics 103(1), 89-99.
    doi: 10.1016/j.ajhg.2018.06.002google scholar: lookup
  31. Williams RD, Morter RL, Freeman MJ, Lavignette AM. Experimental chronic uveitis. Ophthalmic signs following equine leptospirosis. Investigative Ophthalmology 10(12), 948-954.

Citations

This article has been cited 2 times.
  1. 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.
    doi: 10.1111/vop.70132pubmed: 41518147google scholar: lookup
  2. 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.
    doi: 10.1186/s12864-025-12099-3pubmed: 41068571google scholar: lookup
Subscribe to our newsletter
Join 99,001 horse owners like you who receive our email updates on horse health and nutrition.