• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Predicting mutation outcome from early stochastic variation in genetic interaction partners
【24h】

Predicting mutation outcome from early stochastic variation in genetic interaction partners

机译：预测基因相互作用伙伴中早期随机变异的突变结果

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

Many mutations, including those that cause disease, only have a detrimental effect in a subset of individuals. The reasons for this are usually unknown, but may include additional genetic variation and environmental risk factors. However, phenotypic discordance remains even in the absence of genetic variation, for example between monozygotic twins, and incomplete penetrance of mutations is frequent in isogenic model organisms in homogeneous environments. Here we propose a model for incomplete penetrance based on genetic interaction networks. Using Caenorhabditis elegans as a model system, we identify two compensation mechanisms that vary among individuals and influence mutation outcome. First, feedback induction of an ancestral gene duplicate differs across individuals, with high expression masking the effects of a mutation. This supports the hypothesis that redundancy is maintained in genomes to buffer stochastic developmental failure. Second, during normal embryonic development we find that there is substantial variation in the induction of molecular chaperones such as Hsp90 (DAF-21). Chaperones act as promiscuous buffers of genetic variation, and embryos with stronger induction of Hsp90 are less likely to be affected by an inherited mutation. Simultaneously quantifying the variation in these two independent responses allows the phenotypic outcome of a mutation to be more accurately predicted in individuals. Our model and methodology provide a framework for dissecting the causes of incomplete penetrance. Further, the results establish that inter-individual variation in both specific and more general buffering systems combine to determine the outcome inherited mutations in each individual.
机译：许多突变，包括引起疾病的突变，仅对一部分个体产生有害影响。其原因通常是未知的，但可能包括其他遗传变异和环境风险因素。然而，即使在没有遗传变异的情况下，例如在单卵双胞胎之间，仍然存在表型不一致，并且在均质环境中的等基因模型生物中，突变的不完全渗透率很常见。在这里，我们提出了一种基于遗传相互作用网络的不完全渗透率模型。使用秀丽隐杆线虫作为模型系统，我们确定了两种补偿机制，这些机制在个体之间会有所不同并影响突变结果。首先，祖先基因重复的反馈诱导在个体之间是不同的，高表达掩盖了突变的影响。这支持了这样的假设，即在基因组中保留了冗余以缓冲随机的发育失败。其次，在正常的胚胎发育过程中，我们发现分子伴侣（例如Hsp90（DAF-21））的诱导存在很大差异。伴侣蛋白充当遗传变异的混杂缓冲液，具有更强Hsp90诱导作用的胚胎受遗传突变的影响较小。同时量化这两个独立响应中的变异，可以在个体中更准确地预测突变的表型结果。我们的模型和方法论为剖析不完全外显的原因提供了一个框架。此外，结果证实，特定缓冲液系统和更通用缓冲系统中的个体间变异共同决定了每个个体的结果遗传突变。

著录项

  • 来源
    《Nature》 |2011年第7376期|p.250-253|共4页
  • 作者

    Alejandro Burga; M. Olivia Casanueva; Ben Lehner;

  • 作者单位

    EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain;

    EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain;

    EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain,lnstituci6 Catalana de Recerca i Estudis Avancats, Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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