环境因素可导致基因损伤变异并诱发癌症，而在基因组范围且单碱基水平检测环境所致遗传学损伤的关键技术尚缺。申请人在环境生物学(Environ. Mol. Mutagen. 2011)、基因组学(Genome Biol. 2015)、二代测序(Bioinformatics 2016)领域较有积累。前期我们开发了靶向基因组分子条形码测序技术，该技术优于经典遗传毒理学检测方法Ames assay，能精准检测到化合物ENU所致的鼠伤寒沙门氏菌基因突变图谱梯度。本项目中，我们将确定环境因素特异的靶向基因组区域；提高不同来源DNA的分子条形码测序文库构建效率；在原核生物、体外培养细胞、动物及人体等几个不同层次确定该技术的灵敏度与准确性；选取长期暴露于环境污染物的个体及群体开展实地检测；建立可用于人体标本检测的规范流程；并阐明环境因素发挥遗传学毒性的机制。该项目将为环境因素所致基因损伤的检测提供技术保障。

Environmental pollutants have the potential to damage genetic material DNA, and eventually lead to cancer incidence. Currently the technique is still unavailable to detect genetic damages at genome scale and base resolution. The applicant has accumulated plenty of experiences in the fields of environmental biology, genomics and next-generation sequencing. In the pilot studies we developed the target-genome molecular-barcoding sequencing (TMA) assay, and compared its performance with the canonical genetic toxicity test, Ames assay, and found TMA assay could detect the mutational spectra in ENU-treated Salmonella typhimurium. In this project, we will determine the environmental factor-susceptible genome regions, improve the efficacy of constructing molecularly barcoded sequencing library from various sources of DNA, evaluate its sensitivity and accuracy in bacteria, in-vitro cultured cells, animals, and human peripheral blood, select the individuals or population who were long term exposed to environmental pollutants for genetic damage detection, and demonstrate the mechanisms by which environmental pollutants exert their genetic damages. This project will provide technical supports for the detection of environmental pollutants-induced genetic damages.