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Journal of Animal Science Abstract - Animal Genetics and Genomics

Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse1

 

This article in JAS

  1. Vol. 95 No. 3, p. 1071-1079
     
    Received: Nov 21, 2016
    Accepted: Jan 10, 2017
    Published: March 28, 2017


    2 Corresponding author(s): samantha.brooks@ufl.edu
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doi:10.2527/jas2016.1221
  1. S. L. Lewis*,
  2. H. M. Holl*,
  3. C. Streeter,
  4. C. Posbergh,
  5. B. J. Schanbacher,
  6. N. J. Place,
  7. M. F. Mallicote§,
  8. M. T. Long# and
  9. S. A. Brooks 2*
  1. * Department of Animal Sciences, University of Florida, Gainesville 32611
     Department of Animal Sciences, Cornell University, Ithaca, NY 14853
     Department of Population Medicine & Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
    § Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32611
    # Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville 32611

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 (FAM174A) 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 (P = 0.0024 and P = 9.663 × 10−7, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values (P = 0.0056) and BCS (P = 0.0063). Screening of the predicted FAM174A 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 FAM174A was correlated with elevated insulin values in the GWAS population (P = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 (P = 0.0055 and P = 0.0162, respectively). The BIEC2-263524-C and the FAM174A 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.

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