S1: Use of genomic dose-response for hazard characterization
Use of genomic dose-response for hazard characterization at the NTP
North Carolina State University
There is strong evidence that gene-environment interactions (GxE) play an important role in health outcomes and that differential susceptibility following exposure to certain chemicals can be directly related to population genetic variation. However, there remain challenges in detecting and characterizing GxE related to chemical exposure. Recent advancements in high-throughput screening (HTS) technologies using zebrafish (D. rerio) have the potential to address GxE questions across large chemical sets. Zebrafish populations differ from many model organisms in that the standard husbandry practices are designed to maintain diversity, meaning that most laboratory populations contain an unknown level of genetic diversity. This population genetic diversity is attractive in translating to questions of human and ecological safety assessment, where it can be used to address how interindividual genetic variation might contribute to susceptibility differences in response to chemical exposure. Here, we present results from whole-genome sequencing of a large sample of individual zebrafish exposed to different environmental conditions. We show that differential susceptibility can be associated with naturally-occurring, population genetic variation. Our results demonstrate that GxE play a role in mediating response to chemical exposure and has implications for both human health and ecological species. Further, our observations suggest that interindividual genetic diversity within laboratory populations may be higher than currently estimated and may have implications for differential susceptibility observed in toxicological studies.