Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH)

PLoS One. 2016 Apr 12;11(4):e0152966. doi: 10.1371/journal.pone.0152966. eCollection 2016.

Abstract

While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Genes, DCC
  • Genome-Wide Association Study
  • Horse Diseases / genetics*
  • Horse Diseases / immunology
  • Horses / genetics
  • Horses / immunology
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Hypersensitivity / veterinary*
  • Inbreeding
  • Insect Bites and Stings / genetics
  • Insect Bites and Stings / immunology
  • Insect Bites and Stings / veterinary*
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Skin Diseases, Genetic / genetics
  • Skin Diseases, Genetic / immunology
  • Skin Diseases, Genetic / veterinary

Grants and funding

The research leading to these results has received funding from the European Union's Seventh Framework Programme managed by REA-Research Executive Agency, http://ec.europa.eu/research/rea (FP7/2007-2013) under grant agreement no. [606142], The Exmoor Pony Society in UK, The Swedish Research Council (FORMAS), and European Graduate School of Animal Breeding and Genetics (EGS-ABG). Animal DNA Diagnostics, the current employer of JES, had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section and occurred during the author’s tenure at the Animal Health Trust.