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

individual patients vary in their responses to bleomycin. The identification of genetic differences 48 that underlie this response variation could improve treatment outcomes by tailoring bleomycin 49 dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic 50 determinants of bleomycin-response differences by performing linkage mapping on 51 recombinants derived from a cross between the laboratory strain (N2) and a wild strain 52 (CB4856). This approach identified a small genomic region on chromosome V that underlies 53 bleomycin-response variation. Using near-isogenic lines and strains with CRISPR-Cas9 54 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene 55 (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes 56 variation in bleomycin responses is unknown, we suggest that a rare variant present in the 57 CB4856 strain might cause differences in the potential stress-response function of scb-1 between 58 the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance. 59 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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