Whole-Genome Profiling of Mutagenesis in Caenorhabditis elegans

Author:

Flibotte Stephane12,Edgley Mark L3,Chaudhry Iasha3,Taylor Jon3,Neil Sarah E3,Rogula Aleksandra3,Zapf Rick3,Hirst Martin2,Butterfield Yaron2,Jones Steven J2,Marra Marco A2,Barstead Robert J4,Moerman Donald G13

Affiliation:

1. Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada

2. Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada

3. Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada and

4. Department of Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Genetics

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