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Animal genetics2022; 53(3); 436-440; doi: 10.1111/age.13200

A genetic investigation of equine recurrent uveitis in the Icelandic horse breed.

Abstract: Equine recurrent uveitis (ERU) is an autoimmune disease defined by inflammation of the uveal tract of the eye. The cause of ERU is thought to be complex, involving both genetic and environmental factors. The purpose of this study was to investigate potential genetic risk factors for ERU in the Icelandic horse. Fifty-six Icelandic horses (11 affected with ERU and 45 controls) living in Denmark and the USA, eight years or older, were included in the study. A case-control GWAS was performed using the GGP Equine 80K array on the Illumina Infinium HD Beadchip using 40 horses. A mixed linear model analysis identified a single SNP on ECA 11 (BIEC2_141650; NC_009154.3:g.3817009A>G) that reached genome-wide significance (p = 1.79 × 10-7 ). This variant was within an intron of tissue inhibitor of metalloproteinase 2 (TIMP2), a gene previously implicated in ERU. Sanger sequencing identified a single coding variant in this gene; however it was a synonymous mutation (NC_009154.3:g.3858193C>T) and was not perfectly concordant with ERU phenotype (p = 0.68). Further investigation of TIMP2 is warranted. Additional horses and markers are needed to identify other potential loci worthy of further investigation as contributors to ERU risk in Icelandic horses.
© 2022 Stichting International Foundation for Animal Genetics.
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Publication Date: 2022-04-22 PubMed ID: 35451153DOI: 10.1111/age.13200Google Scholar: Lookup
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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 seeks to understand the genetic factors that could potentially contribute to equine recurrent uveitis (ERU), an autoimmune eye disease, in Icelandic horses. Using gene mapping and sequencing, a significant variant was identified in the gene TIMP2, previously linked to ERU.

Understanding the Research Scope and Background

  • The study aimed to understand if genetic factors play a significant role in development of equine recurrent uveitis (ERU), which is an autoimmune disease causing inflammation in the uveal tract of a horse’s eye.
  • The focus of the study was the Icelandic horse breed. A total of 56 Icelandic horses in Denmark and the USA, including both disease-affected and healthy individuals, were chosen for this research.
  • Earlier research has suggested that ERU’s underlying causes might include both genetic as well as environmental factors, providing the impetus for this more focused genetic study.

Methodology of the Study

  • The researchers conducted a Genome-Wide Association Study (GWAS), a type of study that involves rapidly scanning markers across complete sets of DNA (or genomes) of many individuals to find genetic variations associated with a particular disease.
  • The research used the GGP Equine 80K array, part of a high definition gene reader (Illumina Infinium HD Beadchip), using 40 horses from the initial 56.
  • A complex statistical model (a mixed linear model analysis) was used to identify if there were any particular ‘Single Nucleotide Polymorphisms’ (SNPs) – variations occurring at a single position in a DNA sequence – that were significantly associated with the occurrence of ERU.

Findings and Interpretation

  • The researchers found a single SNP on ECA 11 (identified as BIEC2_141650, or NC_009154.3:g.3817009A>G) that showed genome-wide significance. In simple terms, this means this particular variation was significantly associated with ERU in the sample group, over and above what one might expect by chance.
  • This variant was located within an intron of the ‘Tissue Inhibitor of Metalloproteinase 2’ (TIMP2) gene, which has been previously implicated in ERU. Introns are non-protein-coding regions of genes.
  • Despite further sequencing revealing a potential variant in the TIMP2 gene coding region, it turned out to be a synonymous mutation (it wouldn’t change the protein made by the gene). Also, its relationship with ERU wasn’t statistically significant.

Conclusions and Further Steps

  • Even though a connection has been established between the TIMP2 gene and ERU, the significance of the synonymous mutation in the gene remains unclear, thus necessitating further investigation.
  • The study also suggests that additional research involving a larger number of horses and more genetic markers could shed light on other genetic loci that might influence the risk of ERU in Icelandic horses.

Cite This Article

APA
Hack Y, Henriksen ML, Pihl TH, Nielsen RK, Dwyer AE, Bellone RR. (2022). A genetic investigation of equine recurrent uveitis in the Icelandic horse breed. Anim Genet, 53(3), 436-440. https://doi.org/10.1111/age.13200

Publication

Animal genetics
ISSN: 1365-2052
NlmUniqueID: 8605704
Country: England
Language: English
Volume: 53
Issue: 3
Pages: 436-440

Researcher Affiliations

Hack, Yael
  • 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.
Henriksen, Michala de Linde
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Pihl, Tina Holberg
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Nielsen, Rikke Krarup
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Dwyer, Ann E
  • Genesee Valley Equine Clinic, LLC, Scottsville, New York, 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

  • Animals
  • Case-Control Studies
  • Horse Diseases / genetics
  • Horses / genetics
  • Iceland
  • Tissue Inhibitor of Metalloproteinase-2
  • Uveitis / genetics
  • Uveitis / veterinary

Grant Funding

  • KUSTOS af 1881 Foundation, Denmark

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Citations

This article has been cited 2 times.
  1. Hansen S, Hopster-Iversen C, Berg L, Fjeldborg J, Massey C, Piercy RJ, Carstensen H. Chronic idiopathic myopathy in Icelandic horses: A case series. Equine Vet J 2025 Sep;57(5):1341-1346.
    doi: 10.1111/evj.14519pubmed: 40275651google scholar: lookup
  2. Cassano JM, Leonard BC, Martins BC, Vapniarsky N, Morgan JT, Dow SW, Wotman KL, Pezzanite LM. Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis. Front Vet Sci 2023;10:1293199.
    doi: 10.3389/fvets.2023.1293199pubmed: 38162475google scholar: lookup
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