The Million Mutation Project: A new approach to genetics in Caenorhabditis elegans
- Owen Thompson1,
- Mark Edgley2,
- Pnina Strasbourger1,
- Stephane Flibotte2,
- Brent Ewing3,
- Ryan Adair2,
- Vinci Au2,
- Iasha Chaudry2,
- Lisa Fernando2,
- Harald Hutter4,
- Armelle Kieffer2,
- Joanne Lau2,
- Norris Lee2,
- Angela Miller2,
- Greta Raymant2,
- Bin Shen2,
- Jay Shendure3,
- Jon Taylor2,
- Emily Turner3,
- LaDeana Hillier3,
- Donald G. Moerman2 and
- Robert H. Waterston3,5
- 1 University of Washington;
- 2 University of British Columbia;
- 3 Universtity of Washington;
- 4 Simon Fraser University
- ↵* Corresponding author; email: waterston{at}gs.washington.edu
Abstract
We have created a library of 2,007 mutagenized C. elegans strains, each sequenced to a target depth of 15-fold coverage, to provide the research community with mutant alleles for each of the worm's more than 20,000 genes. The library contains over 800,000 unique single nucleotide variants (SNVs) with an average of 8 non-synonymous changes per gene and more than 16,000 insertion/deletion (indel) and copy number changes, providing an unprecedented genetic resource for this multicellular organism. To supplement this collection, we also sequenced 40 wild isolates, identifying more than 630,000 unique SNVs and 220,000 indels. Comparison of the two sets demonstrates that the mutant collection has a much richer array of both nonsense and missense mutations than the wild isolate set. We also find a wide range of rDNA and telomere repeat copy number in both sets. Scanning the mutant collection for molecular phenotypes reveals a nonsense suppressor as well as strains with higher levels of indels that harbor mutations in DNA repair genes and strains with abundant males associated with him mutations. All the strains are available through the Caenorhabditis Genetics Center and all the sequence changes have been deposited in WormBase and are available through an interactive web site.
- Received March 18, 2013.
- Accepted June 17, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
