Expanding whole exome resequencing into non-human primates
Expanding whole exome resequencing into non-human primates
复制标题
DOI：
10.1186/gb-2011-12-9-r87
复制
发表时间：
2011-01-01
期刊：
影响因子：
12.3
通讯作者：
Vallender, Eric J.
中科院分区：
文献类型：
--
作者：
Vallender, Eric J.
背景：完整的外显子组重测序有能力极大地扩展我们对非人类灵长类基因组的理解。这既包括对存在于非人类灵长类模式物种中的变异的更好的欣赏，也包括对它们基因组的改进注释。通过发展对个体之间差异的理解，可以更好地开发人类疾病的非人类灵长类动物模型。这一努力在很大程度上受到缺乏关于特定的非人类灵长类基因变异的全面信息以及产生这些数据的成本的阻碍。如果已经在人类身上开发的完全外显子组重新测序的工具可以应用于密切相关的非人类灵长类物种，那么这些困难就可以被绕过。结果：使用人类完整外显子组浓缩技术，黑猩猩和恒河猴样本与人类样本一起被捕获，并使用标准的下一代方法进行测序。然后对这三个物种的结果进行疗效比较。黑猩猩样本在基于人类基因组的外显子组捕获后显示出与人类样本相似的复盖水平和分布。恒河猴样本在蛋白质编码序列上的覆盖率很高，但在非翻译区的覆盖率明显较低。与自身基因组相比，黑猩猩和恒河猴都显示了大量的移码突变，这表明需要进一步的注释。结论：目前的整个外显子组重测序技术可以成功地用于识别延伸到东半球猴子的非人类灵长类动物的编码区变异。除了识别变异，整个外显子组重测序还可以帮助更好地注释非人类灵长类基因组。
Background: Complete exome resequencing has the power to greatly expand our understanding of non-human primate genomes. This includes both a better appreciation of the variation that exists in non-human primate model species, but also an improved annotation of their genomes. By developing an understanding of the variation between individuals, non-human primate models of human disease can be better developed. This effort is hindered largely by the lack of comprehensive information on specific non-human primate genetic variation and the costs of generating these data. If the tools that have been developed in humans for complete exome resequencing can be applied to closely related non-human primate species, then these difficulties can be circumvented.Results: Using a human whole exome enrichment technique, chimpanzee and rhesus macaque samples were captured alongside a human sample and sequenced using standard next-generation methodologies. The results from the three species were then compared for efficacy. The chimpanzee sample showed similar coverage levels and distributions following exome capture based on the human genome as the human sample. The rhesus macaque sample showed significant coverage in protein-coding sequence but significantly less in untranslated regions. Both chimpanzee and rhesus macaque showed significant numbers of frameshift mutations compared to self-genomes and suggest a need for further annotation.Conclusions: Current whole exome resequencing technologies can successfully be used to identify coding-region variation in non-human primates extending into old world monkeys. In addition to identifying variation, whole exome resequencing can aid in better annotation of non-human primate genomes.