An inversion disrupting FAM134B is associated with sensory neuropathy in the Border Collie dog breed

Forman, O. P., Hitti, R. J., Pettitt, L., Jenkins, C. A., O'Brien, D. P., Shelton, G. D., De Risio, L., Gutierrez Quintana, R. , Beltran, E. and Mellersh, C. (2016) An inversion disrupting FAM134B is associated with sensory neuropathy in the Border Collie dog breed. G3: Genes, Genomes, Genetics, 6(9), pp. 2687-2692. (doi: 10.1534/g3.116.027896) (PMID:27527794) (PMCID:PMC5015927)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gutierrez Quintana, Mr Rodrigo
• Authors: Forman, O. P., Hitti, R. J., Pettitt, L., Jenkins, C. A., O'Brien, D. P., Shelton, G. D., De Risio, L., Gutierrez Quintana, R., Beltran, E., and Mellersh, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: G3: Genes, Genomes, Genetics
• Publisher: Genetics Society of America
• ISSN: 2160-1836
• ISSN (Online): 2160-1836
• Published Online: 15 August 2016
• Copyright Holders: Copyright © 2016 Forman et al.
• First Published: First published in G3: Genes, Genomes, Genetics 6(9):2687-2692
• Publisher Policy: Reproduced under a Creative Commons License