Direct Somatic Mutation Analysis Through Sequencing

描述(由申请人提供)：缺乏快速、准确和经济高效地评估人类诱变结果的技术，基本上限制了对个人对环境诱变剂的易感性及其与癌症、遗传病和老龄化的关系的更全面的了解。一种直接在人类血液或组织样本中测量突变频率和光谱的检测方法，将提供有关先前暴露于环境诱变剂的信息，与个人不同的基因组维持途径阵列的状态有关。这将使以人群为基础的研究、临床研究和常规生物监测能够进行风险评估。在这里，我们建议开发一种高灵敏度、健壮和可扩展的方法，通过序列捕获和大规模并行测序(SC-MPS)直接测量人类细胞或组织中的DNA突变。 与公共卫生相关：人类暴露在多种环境诱变剂和致癌物中。我们建议开发一种方法，允许直接测量人类血液或组织样本中的DNA突变负载，而不需要进行选择。这应该提供一种可靠且经济有效的方法来评估个体的人类风险，例如，在可能暴露于诱变剂之后。

DESCRIPTION (provided by applicant): The lack of technology to rapidly, accurately and cost-effectively assess mutagenic outcomes in humans has essentially constrained a more complete understanding of individual susceptibility to environmental mutagens and their relationship to cancer, genetic disease and aging. An assay to measure mutation frequency and spectrum directly in human blood or tissue samples would provide information about previous exposures to environmental mutagens in relation to the status of an individual's diverse array of genome maintenance pathways. This would enable human population-based studies, clinical studies and routine biomonitoring for risk assessment. Here we propose to develop a highly sensitive, robust and scalable assay for directly measuring DNA mutations in human cells or tissues by sequence capture and massively parallel sequencing (SC-MPS). PUBLIC HEALTH RELEVANCE: Humans are exposed to a large variety of environmental mutagens and carcinogens. We propose to develop a method that allows measuring DNA mutation load in human blood or tissue samples directly, without selection. This should provide a robust and cost-effective assay to assess individual human risk, for example, after possible exposure to mutagens.