Direct Somatic Mutation Analysis Through Sequencing

描述（由申请人提供）：缺乏快速、准确和具有成本效益地评估人类诱变结果的技术，基本上限制了对环境诱变剂个体易感性及其与癌症、遗传疾病和衰老关系的更全面了解。直接测量人类血液或组织样本中的突变频率和谱的测定将提供关于先前暴露于环境诱变剂的信息，其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、临床研究和用于风险评估的常规生物监测成为可能。在这里，我们建议开发一种高度灵敏、稳健和可扩展的检测方法，用于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。 公共卫生相关性：人类暴露于各种环境诱变剂和致癌物。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突变负荷，而无需选择。这将提供一种稳健且具有成本效益的测定方法，以评估个体人类风险，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.