• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Human mutation >Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon
【24h】

Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon

机译：非参考LINE-1反转录转座子产生的致病性孤儿转导

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17% of the human genome, and move by a potentially mutagenic "copy and paste" mechanism via an RNA intermediate. Recently, the retrotransposition-mediated insertion of a new transcript was described as a novel cause of genetic disease, Duchenne muscular dystrophy, in a Japanese male. The inserted sequence was presumed to derive from a single-copy, noncoding RNA transcribed from chromosome 11q22.3 that retrotransposed into the dystrophin gene. Here, we demonstrate that a nonreference fulllength LINE-1 is situated in the proband and maternal genome at chromosome 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene. This LINE-1 is highly active in a cell culture assay. LINE-1 insertions are often associated with 3' transduction of adjacent genomic sequences. Thus, the likely explanation for the mutagenic insertion is a LINE-1-mediated 3' transduction with severe 5' truncation. This is the first example of LINE-1-induced human disease caused by an "orphan" 3' transduction.
机译：长的Intersperseded Element-1（LINE-1）逆转座子占人类基因组的17％，并通过潜在的诱变“复制和粘贴”机制通过RNA中间体移动。最近，在日本男性中，逆转录转座介导的新转录本的插入被描述为遗传疾病的新病因，杜氏肌营养不良症。据推测，插入的序列来自单拷贝的非编码RNA，该RNA是从染色体11q22.3转录而来，逆转录成肌营养不良蛋白基因。在这里，我们证明了一个非参考全长LINE-1位于先证者和母体基因组中的染色体11q22.3处，直接在该序列的上游，其副本已插入到肌营养不良蛋白基因中。此LINE-1在细胞培养测定中具有很高的活性。 LINE-1插入通常与相邻基因组序列的3'转导有关。因此，诱变插入的可能解释是LINE-1介导的3'转导，带有严重的5'截短。这是由“孤儿” 3'转导引起的LINE-1诱导的人类疾病的第一个例子。

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