...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>PLoS Genetics >Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs
【24h】

Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs

机译：犬的表征<斜视> kcnip4 ：通过全基因组测序鉴定的小脑共济失调的一种新基因两次受影响的挪威布尔沟犬

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A form of hereditary cerebellar ataxia has recently been described in the Norwegian Buhund dog breed. This study aimed to identify the genetic cause of the disease. Whole-genome sequencing of two Norwegian Buhund siblings diagnosed with progressive cerebellar ataxia was carried out, and sequences compared with 405 whole genome sequences of dogs of other breeds to filter benign common variants. Nine variants predicted to be deleterious segregated among the genomes in concordance with an autosomal recessive mode of inheritance, only one of which segregated within the breed when genotyped in additional Norwegian Buhunds. In total this variant was assessed in 802 whole genome sequences, and genotyped in an additional 505 unaffected dogs (including 146 Buhunds), and only four affected Norwegian Buhunds were homozygous for the variant. The variant identified, a T to C single nucleotide polymorphism (SNP) (NC_006585.3:g.88890674T&C), is predicted to cause a tryptophan to arginine substitution in a highly conserved region of the potassium voltage-gated channel interacting protein KCNIP4. This gene has not been implicated previously in hereditary ataxia in any species. Evaluation of KCNIP4 protein expression through western blot and immunohistochemical analysis using cerebellum tissue of affected and control dogs demonstrated that the mutation causes a dramatic reduction of KCNIP4 protein expression. The expression of alternative KCNIP4 transcripts within the canine cerebellum, and regional differences in KCNIP4 protein expression, were characterised through RT-PCR and immunohistochemistry respectively. The voltage-gated potassium channel protein KCND3 has previously been implicated in spinocerebellar ataxia, and our findings suggest that the Kv4 channel complex KCNIP accessory subunits also have an essential role in voltage-gated potassium channel function in the cerebellum and should be investigated as potential candidate genes for cerebellar ataxia in future studies in other species.
机译：最近在挪威布尔德犬养殖中描述了一种遗传性小脑共济失调的形式。本研究旨在识别疾病的遗传原因。进行了诊断患有渐进式小脑共济失纲目的两种挪威布尔兄弟的全基因组测序，与其他品种的其他品种的狗的405个全基因组序列相比，过滤良性常见变体。预测九种变体预测，在基因组中，通过常染色体隐性遗传模式，只有其中一个在额外的挪威布尔顺利的基因分型时在品种中隔离。总共在802个全基因组序列中评估该变体，并在另外的505只未受影响的犬（包括146个福尔岛）中的基因分型，并且只有四个受影响的挪威丁德斯对于该变体纯合。预测鉴定的变体，T至C单核苷酸多态性（SNP）（NC_006585.3：G.8890674T＆GT; C），使色氨酸在钾电压门控通道相互作用蛋白Kcnip4的高度保守区域中对精氨酸取代。该基因尚未以前在任何物种中以遗传的共济失调涉及。通过患有受影响和对照犬的小脑组织的蛋白质印迹和免疫组织化学分析评价KCNIP4蛋白表达证明了突变导致KCNIP4蛋白表达的显着降低。通过RT-PCR和免疫组化，表征在犬小脑中的替代KCNIP4转录物和KCNIP4蛋白表达的区域差异。电压门控钾通道蛋白KcND3先前涉及纺丝大脑贫困，并且我们的研究结果表明，KV4通道综合kcnip辅助亚基在小脑中的电压门控钾通道功能中也具有重要作用，并且应该被调查为潜在的候选者在其他物种的未来研究中的小脑共济失调基因。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号