A novel 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*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Bleomycin is a powerful chemotherapeutic drug used to treat a variety of cancers. However, individual patients vary in their responses to bleomycin. The identification of genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic determinants of bleomycin-response differences by performing linkage mapping on recombinants derived from a cross between the laboratory strain (N2) and a wild strain (CB4856). This approach identified a small genomic region on chromosome V that underlies bleomycin-response variation. Using near-isogenic lines, and strains with CRISPR-Cas9 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes variation in bleomycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause differences in the potential stress-response function of scb-1 between the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance.

Original languageEnglish (US)
Pages (from-to)1453-1468
Number of pages16
JournalGenetics
Volume212
Issue number4
DOIs
StatePublished - Jan 1 2019

Keywords

  • C. elegans bleomycin
  • Drug-response
  • Linkage mapping
  • QTL

ASJC Scopus subject areas

  • Genetics

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