Direct Somatic Mutation Analysis Through Sequencing

描述（由申请人提供）：缺乏快速、准确和经济有效地评估人类诱变结果的技术，从根本上限制了对个体对环境诱变剂的易感性及其与癌症、遗传疾病和衰老的关系的更全面理解。在人类血液或组织样本中直接测量突变频率和频谱的分析将提供有关先前暴露于环境诱变剂的信息，这些信息与个体的多种基因组维持途径的状态有关。这将使基于人群的研究、临床研究和常规生物监测的风险评估成为可能。在这里，我们建议开发一种高度敏感，稳健和可扩展的方法，通过序列捕获和大规模平行测序（SC-MPS）直接测量人类细胞或组织中的DNA突变。

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.