title: An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.
abstract: Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population.
authors.affiliation: Kennel Club Genetics Centre, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, United Kingdom oliver.forman@effem.com.
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Forman
authors.affiliation: Kennel Club Genetics Centre, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, United Kingdom.
authors.forename: Rebekkah J
authors.initials: RJ
authors.lastname: Hitti
authors.affiliation: Kennel Club Genetics Centre, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Pettitt
authors.affiliation: Kennel Club Genetics Centre, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, United Kingdom.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Jenkins
authors.affiliation: College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: O'Brien
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, California 92093-0709.
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.affiliation: Department of Neurology, Small Animal Clinic, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, United Kingdom.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Risio
authors.affiliation: The School of Veterinary Medicine, University of Glasgow, G61 1QH, United Kingdom.
authors.forename: Rodrigo Gutierrez
authors.initials: RG
authors.lastname: Quintana
authors.affiliation: Department of Clinical Science and Services, Royal Veterinary College, University of London, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.
authors.forename: Elsa
authors.initials: E
authors.lastname: Beltran
authors.affiliation: Kennel Club Genetics Centre, Animal Health Trust, Newmarket, Suffolk, CB8 7UU, United Kingdom.
authors.forename: Cathryn
authors.identifier: 0000-0002-2336-0370
authors.initials: C
authors.lastname: Mellersh
mesh_terms: D000818:Animals; D001483:Base Sequence; D001947:Breeding; D007446:Chromosome Inversion / Q000235:genetics; D002874:Chromosome Mapping; D004285:Dogs; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000473:pathology / Q000662:veterinary; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D009046:Motor Neurons / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C522691:RETREG1 protein, human; D022821:RNA Splice Sites
keywords: FAM134B; GWAS; canine; genome sequencing; sensory neuropathy