title: Whole-genome profiling of mutagenesis in Caenorhabditis elegans.
abstract: Deep sequencing offers an unprecedented view of an organism's genome. We describe the spectrum of mutations induced by three commonly used mutagens: ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), and ultraviolet trimethylpsoralen (UV/TMP) in the nematode Caenorhabditis elegans. Our analysis confirms the strong GC to AT transition bias of EMS. We found that ENU mainly produces A to T and T to A transversions, but also all possible transitions. We found no bias for any specific transition or transversion in the spectrum of UV/TMP-induced mutations. In 10 mutagenized strains we identified 2723 variants, of which 508 are expected to alter or disrupt gene function, including 21 nonsense mutations and 10 mutations predicted to affect mRNA splicing. This translates to an average of 50 informative mutations per strain. We also present evidence of genetic drift among laboratory wild-type strains derived from the Bristol N2 strain. We make several suggestions for best practice using massively parallel short read sequencing to ensure mutation detection.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Stephane
authors.initials: S
authors.lastname: Flibotte
authors.forename: Mark L
authors.initials: ML
authors.lastname: Edgley
authors.forename: Iasha
authors.initials: I
authors.lastname: Chaudhry
authors.forename: Jon
authors.initials: J
authors.lastname: Taylor
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Neil
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rogula
authors.forename: Rick
authors.initials: R
authors.lastname: Zapf
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.forename: Yaron
authors.initials: Y
authors.lastname: Butterfield
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Jones
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Barstead
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D016678:Genome; D016296:Mutagenesis; D009153:Mutagens; D009154:Mutation; D010641:Phenotype; D014307:Trioxsalen
chemical_list: D009153:Mutagens; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D014307:Trioxsalen