title: Using an Inbred Horse Breed in a High Density Genome-Wide Scan for Genetic Risk Factors of Insect Bite Hypersensitivity (IBH).
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.
authors.affiliation: Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Velie
authors.affiliation: Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Merina
authors.initials: M
authors.lastname: Shrestha
authors.affiliation: Research Group Livestock Genetics, Department of Biosystems, KU Leuven, Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Franҫois
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen University, Wageningen, the Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Schurink
authors.affiliation: Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Yohannes G
authors.initials: YG
authors.lastname: Tesfayonas
authors.affiliation: Research Group Livestock Genetics, Department of Biosystems, KU Leuven, Leuven, Belgium.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Stinckens
authors.affiliation: School of Veterinary Medicine & Science, University of Nottingham, Leicestershire, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Blott
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen University, Wageningen, the Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Ducro
authors.affiliation: Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mikko
authors.affiliation: Exmoor Pony Society, Cullompton, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Animal DNA Diagnostics Ltd, Cambridgeshire, United Kingdom.|Animal Health Trust, Newmarket, United Kingdom.
authors.forename: June E
authors.initials: JE
authors.lastname: Swinburne
authors.affiliation: Östra Greda Research Group, Borgholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Sundqvist
authors.affiliation: Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Eriksson
authors.affiliation: Research Group Livestock Genetics, Department of Biosystems, KU Leuven, Leuven, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Buys
authors.affiliation: Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lindgren
mesh_terms: D000818:Animals; D005260:Female; D016163:Genes, DCC; D055106:Genome-Wide Association Study; D006734:Horse Diseases / Q000235:genetics* / Q000276:immunology; D006736:Horses / Q000235:genetics / Q000276:immunology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D007178:Inbreeding; D007299:Insect Bites and Stings / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000276:immunology / Q000662:veterinary