An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed
An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed
复制标题
DOI：
10.1534/g3.116.027896
复制
发表时间：
2016-09-01
影响因子：
2.6
通讯作者：
Mellersh, Cathryn
中科院分区：
文献类型：
--
作者：
Forman, Oliver P.;Hitti, Rebekkah J.;Mellersh, Cathryn
边境牧羊犬的感觉神经病是一种严重的神经系统疾病，由感觉神经细胞和较小程度的运动神经细胞退化引起，临床症状在 2 至 7 个月大时开始出现。使用对 3 个病例和 170 个品种匹配对照的全基因组关联研究方法，确定了感觉神经病的暗示位点，并使用基因组测序方法进行了随访。鉴定出破坏候选基因 FAM134B 的倒位。其他病例和对照的基因分型以及 RNAseq 分析提供了强有力的证据，证明倒置是因果关系。 RNAseq 实验鉴定了导致 FAM134B 新外显子转录的隐秘剪接的证据。这项研究通过使用最少的病例集进行绘图和随后的基因组测序，证明了一种新型感觉神经病相关突变的鉴定。通过突变筛选，应该可以减少边境牧羊犬品种群体中这种衰弱状况的发生频率或完全消除这种状况。
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.