Xk469

All dose-response experiments were performed on four genetically diverged strains (Bristol, Hawaii, DL238, and JU258) in technical quadruplicates prior to performing GWA and linkage mapping experiments (S4 Table). Animals were assayed using the HTA, and phenotypic analysis was performed as described above. Drug concentrations for GWA and linkage mapping experiments were chosen based on two criteria—an observable drug-specific effect and broad-sense heritability H². We aimed to use the first concentration for which a drug-specific effect with a maximum H² was observed. Broad-sense heritability estimates were calculated using the lmer function in the lme4 package with the following model (phenotype ~1 + (1|strain)). Concentrations for each chemotherapeutic used in mapping experiments are; etoposide—250 μM, teniposide—125 μM, amsacrine—50 μM, dactinomycin—15 μM, and XK469–1000 μM. All topoisomerase II poisons used in this study were purchased from Sigma (XK469 cat#X3628, etoposide cat#E1383, amsacrine cat#A9809, dactinomycin cat#A1410, and teniposide cat#SML0609).