Application of error-corrected Next-Generation Sequencing for assessing the mutagenic effects of environmental and occupational exposures in human populations

Funding period: 2025-2030
Lead: Francesco Marchetti
Total GRDI funding: $1,088,140

New mutations (changes in DNA sequence) occur at every cell division due to random  errors or exposure to toxic agents. Mutations occurring in tissues may lead to cancer, while those in sperm or eggs can be transmitted to the offspring and cause a variety of genetic diseases. Understanding how environmental and workplace exposures lead to mutations is important to protect the health of Canadians. This project will use new error-corrected Next-Generation Sequencing (ecNGS) approaches to improve our ability to detect rare mutations in human DNA. ecNGS tags individual DNA molecules to identify and remove sequencing errors, enabling accurate mutation detection. The project will study age and exposure-related increases in sperm mutations; the link between years of service and mutations in firefighters' blood; the mutagenic effects of early-life exposures to air pollution on newborns and children; and, the effects of chemotherapy on children. The project will refine Canada's risk assessment tools, enabling targeted regulations to protect Canadians from harmful exposures.