• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Canine Genetics and Epidemiology >A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever
【24h】

A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever

机译：TTC8的新型突变与金毛猎犬中进行性视网膜萎缩有关

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

摘要

BackgroundGeneralized progressive retinal atrophy (PRA) is a group of inherited eye diseases characterised by progressive retinal degeneration that ultimately leads to blindness in dogs. To date, more than 20 different mutations causing canine-PRA have been described and several breeds including the Golden Retriever are affected by more than one form of PRA. Genetically distinct forms of PRA may have different clinical characteristics such as rate of progression and age of onset. However, in many instances the phenotype of different forms of PRA cannot be distinguished at the basic clinical level achieved during routine ophthalmoscopic examination. Mutations in two distinct genes have been reported to cause PRA in Golden Retrievers (prcd-PRA and GR_PRA1), but for approximately 39% of cases in this breed the causal mutation remains unknown. ResultsA genome-wide association study of 10 PRA cases and 16 controls identified an association on chromosome 8 not previously associated with PRA (praw?=?1.30×10-6 and corrected with 100,000 permutations, pgenome?=?0.148). Using haplotype analysis we defined a 737?kb critical region containing 6 genes. Two of the genes ( TTC8 and SPATA7 ) have been associated with Retinitis Pigmentosa (RP) in humans. Using targeted next generation sequencing a single nucleotide deletion was identified in exon 8 of the TTC8 gene of affected Golden Retrievers. The frame shift mutation was predicted to cause a premature termination codon. In a larger cohort, this mutation, TTC8 c.669delA, segregates correctly in 22 out of 29 cases tested (75.9%). Of the PRA controls none are homozygous for the mutation, only 3.5% carry the mutation and 96.5% are homozygous wildtype. ConclusionsOur results show that PRA is genetically heterogeneous in one of the world’s numerically largest breeds, the Golden Retriever, and is caused by multiple, distinct mutations. Here we discuss the mutation that causes a form of PRA, that we have termed PRA2, that accounts for approximately 30% of PRA cases in the breed. The genetic explanation for approximately 9% of cases remains to be identified. PRA2 is a naturally occurring animal model for Retinitis Pigmentosa, and potentially Bardet-Biedl Syndrome.
机译：背景广义进行性视网膜萎缩症（PRA）是一组以眼部进行性视网膜变性为特征的遗传性眼部疾病，最终导致犬的失明。迄今为止，已经描述了引起犬PRA的20多种不同的突变，包括金毛猎犬在内的数个品种都受到一种以上PRA形式的影响。 PRA的遗传学上不同形式可能具有不同的临床特征，例如进展速度和发病年龄。然而，在许多情况下，不能在常规检眼镜检查过程中达到的基本临床水平上区分不同形式PRA的表型。据报道，两个不同基因的突变会在金毛寻回犬中引起PRA（prcd-PRA和GR_PRA1），但是对于该品种中约39％的病例，因果突变仍然未知。结果对10个PRA病例和16个对照的全基因组关联研究确定了先前与PRA无关的8号染色体上的关联（p raw ？=？1.30×10 -6 和校正了100,000个排列，p 基因组？=？0.148）。使用单倍型分析，我们定义了一个包含6个基因的737？kb关键区域。人类中有两个基因（TTC8和SPATA7）与色素性视网膜炎（RP）相关。使用靶向的下一代测序，在受影响的金毛寻回犬的TTC8基因的外显子8中鉴定出单个核苷酸缺失。预计移码突变会引起过早的终止密码子。在更大的队列中，这种突变，TTC8 c.669delA ，在测试的29例病例中有22例正确分离（75.9％）。 PRA对照中没有一个是纯合子突变，只有3.5％携带该突变，而96.5％是纯合子野生型。结论我们的结果表明，PRA在世界上数量最大的品种之一金毛猎犬中具有遗传异质性，并且是由多个不同的突变引起的。在这里，我们讨论引起PRA形式的突变，我们将其称为PRA2，约占该品种PRA病例的30％。大约9％的病例的遗传学解释尚待确定。 PRA2是色素性视网膜炎和潜在的Bardet-Biedl综合征的天然动物模型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 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