1. An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.
- Author
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Forman OP, Hitti RJ, Pettitt L, Jenkins CA, O'Brien DP, Shelton GD, De Risio L, Quintana RG, Beltran E, and Mellersh C
- Subjects
- Animals, Base Sequence, Breeding, Chromosome Inversion genetics, Chromosome Mapping, Dogs, Exons genetics, Female, Genotype, Hereditary Sensory and Autonomic Neuropathies pathology, Hereditary Sensory and Autonomic Neuropathies veterinary, Humans, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Motor Neurons pathology, Mutation, RNA Splice Sites genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Hereditary Sensory and Autonomic Neuropathies genetics, Neoplasm Proteins genetics
- 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., (Copyright © 2016 Forman et al.)
- Published
- 2016
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