A nematode-specific gene underlies bleomycin-response variation in Caenorhabditis elegans

Shannon C. Brady; Stefan Zdraljevic; Karol W. Bisaga; Robyn E. Tanny; Daniel E. Cook; Daehan Lee; Ye Wang; Erik C. Andersen

We performed linkage mapping on the residual median optical density measurements in 460 bleomycin ( Figure S4, Figure S5 , File S4, Materials and Methods) and identified four 461 significant quantitative trait loci (QTL, Figure 1A) . The QTL on the center of chromosome V 462 was highly significant (explained 43.58% of the total variation and 55.60% of the genetic 463 variation) with a LOD score of 32.57, and it was detected for 25 of the 26 HTA traits (Figure S5, 464 File S4). The QTL 95% confidence interval was approximately 147 kb. Strains with the N2 465 allele at the peak marker had a lower median optical density in bleomycin and were interpreted 466 to be more sensitive than those RIAILs with the CB4856 allele ( Figure 1B) . The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/565218 doi: bioRxiv preprint 22 of 48 CB4856 strain and a region of chromosome V from the opposite parental genotype. We used the 471 HTA to test these strains in response to bleomycin (File S3). The NIL with the N2 genotype 472 across this QTL introgressed into the CB4856 background (ECA230) was statistically more 473 sensitive to bleomycin than CB4856 (Figure S6, File S7, p = 1.3e-14, Tukey HSD) . This 474 phenotype indicated that the N2 genotype within the introgressed region (which includes the 475 QTL confidence interval) confers sensitivity to bleomycin. However, the reciprocal NIL with the 476 CB4856 locus introgressed into the N2 background (ECA232) had a bleomycin-response 477 phenotype that was not significantly different from the N2 strain ( Figure S6 , File S7, p = 0.053, 478