Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.
Abstract: Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150-kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and warrants investigation of this locus for a role in metabolic- and obesity-related disorders of other species.
Publication Date: 2017-04-06 PubMed ID: 28380523DOI: 10.2527/jas.2016.1221Google Scholar: Lookup
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- Journal Article
Summary
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The study highlights the discovery of a genetic locus related to equine metabolic syndrome (EMS) in Arabian horses that could potentially be used for early identification and hence, help manage obesity in horses. This was done by conducting a genomewide association study and evaluating certain correlations between identified markers and the disease.
Background of the Study
- The research focuses on equine metabolic syndrome (EMS), a condition prevalent in obese horses and ponies commonly characterized by elevated insulin levels.
- EMS can lead to severe secondary conditions and has clinical similarities with conditions such as pituitary pars intermedia dysfunction, making its diagnosis challenging.
- Given the lack of specific treatments for EMS, the timely identification of potential risk cases can help in the implementation of preventative measures.
Methods and Findings of the Study
- The researchers used a genomewide association study (GWAS) to identify a risk locus for EMS. They examined Arabian horses that had previously suffered from severe laminitis, a condition often associated with EMS.
- They found significant genetic markers close to a particular candidate gene. These markers seemed to play a role in cholesterol regulation within the body.
- The strongest marker, BIEC2-263524, showed a correlation with higher insulin levels and an increased frequency of laminitis. The researchers further confirmed this association in another population of Arabian horses where the marker was related to higher modified insulin-to-glucose ratio (MIRG) values and Body Condition Score (BCS).
- More in-depth examination identified a polymorphic guanine homopolymer and 5 haplotypes in the 3′ untranslated region (UTR). An 11 guanine (11-G) allele at this location also correlated with elevated insulin levels.
Significance and Future Directions
- Screening tests using these identified markers could potentially help diagnose horses that are genetically predisposed to obesity or EMS. This can provide a proactive approach to manage the condition in early stages.
- The identification of the function of FAM174A, the candidate gene identified, could contribute to a better understanding of the origin of EMS and obesity in horses and other species.
- Further investigation of this locus is warranted as it could potentially play a role in obesity and metabolic disorders not just in horses, but in other animal species as well.
Cite This Article
APA
Lewis SL, Holl HM, Streeter C, Posbergh C, Schanbacher BJ, Place NJ, Mallicote MF, Long MT, Brooks SA.
(2017).
Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.
J Anim Sci, 95(3), 1071-1079.
https://doi.org/10.2527/jas.2016.1221 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Horse Diseases / genetics
- Horses
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism
- Metabolic Syndrome / veterinary
- Obesity / genetics
- Obesity / veterinary
Citations
This article has been cited 10 times.- Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine Metabolic Syndrome: A Complex Disease Influenced by Multifactorial Genetic Factors.. Genes (Basel) 2023 Jul 27;14(8).
- Clark BL, Bamford NJ, Stewart AJ, McCue ME, Rendahl A, Bailey SR, Bertin FR, Norton EM. Evaluation of an HMGA2 variant contribution to height and basal insulin concentrations in ponies.. J Vet Intern Med 2023 May-Jun;37(3):1186-1192.
- Hammons V, Ribeiro L, Munyard K, Sadeghi R, Miller D, Antczak D, Brooks SA. GWAS Identifies a Region Containing the SALL1 Gene in Variation of Pigmentation Intensity Within the Chestnut Coat Color of Horses.. J Hered 2021 Aug 25;112(5):443-446.
- Wallis N, Raffan E. The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals.. Genes (Basel) 2020 Nov 20;11(11).
- Todd ET, Thomson PC, Hamilton NA, Ang RA, Lindgren G, Viklund Å, Eriksson S, Mikko S, Strand E, Velie BD. A genome-wide scan for candidate lethal variants in Thoroughbred horses.. Sci Rep 2020 Aug 4;10(1):13153.
- Box JR, McGowan CM, Raekallio MR, Mykkänen AK, Carslake H, Karikoski NP. Insulin dysregulation in a population of Finnhorses and associated phenotypic markers of obesity.. J Vet Intern Med 2020 Jul;34(4):1599-1605.
- Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era.. Anim Genet 2019 Dec;50(6):569-597.
- Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome.. J Vet Intern Med 2019 Mar;33(2):335-349.
- Linn SC, Mustonen AM, Silva KA, Kennedy VE, Sundberg BA, Bechtold LS, Alghamdi S, Hoehndorf R, Schofield PN, Sundberg JP. Nail abnormalities identified in an ageing study of 30 inbred mouse strains.. Exp Dermatol 2019 Apr;28(4):383-390.
- Lewis SL, Holl HM, Long MT, Mallicote MF, Brooks SA. Use of principle component analysis to quantitatively score the equine metabolic syndrome phenotype in an Arabian horse population.. PLoS One 2018;13(7):e0200583.
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