The million mutation project: A new approach to genetics in <i>Caenorhabditis elegans</i>

Thompson, Owen; Edgley, Mark L.; Strasbourger, Pnina; Flibotte, Stéphane; Ewing, Brent; Adair, Ryan; Au, Vinci; Chaudhry, Iasha; Fernando, Lisa; Hutter, Harald; Kieffer, Armelle; Lau, Joanne; Lee, Norris; Miller, Angela; Raymant, Greta; Shen, Bin; Shendure, Jay; Taylor, John; Turner, Emily H.; Hillier, LaDeana W.; Moerman, Donald G.; Waterston, Robert H.

doi:10.1101/gr.157651.113

Cited by 410 publications

(470 citation statements)

References 64 publications

(59 reference statements)

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“…Recently, the Million Mutation Project has identified more than 800,000 new mutations in more than 20,000 C. elegans genes with more than 13 novel non-synonymous alleles per gene. 10 GExplore contains a search interface, "Mutations," to identify the location of mutations in a list of candidate genes (Fig. 2B).…”

Section: Datasets: Mutationsmentioning

confidence: 99%

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GExplore 1.4: An expanded web interface for queries onCaenorhabditis elegansprotein and gene function

Hutter

Suh

2016

Worm

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Genetic high-throughput experiments often result in hundreds or thousands of genes satisfying certain experimental conditions. Grouping and prioritizing a large number of genes for further analysis can be a time-consuming challenge. In 2009 we developed a web-based user interface, GExplore, to assist with large-scale data-mining related to gene function in Caenorhabditis elegans. The underlying database contained information about Caenorhabditis elegans genes and proteins including domain organization of the proteins, phenotypic descriptions, expression data and Gene Ontology Consortium annotations. These data enable users to quickly obtain an overview of biological and biochemical functions of a large number of genes at once. Since its inception the underlying database has been updated and expanded significantly. Here we describe the current version of GExplore 1.4, documenting the changes since the original release. GExplore 1.4 now contains information about the domain organization of the proteomes of 9 nematode species, can display the location of Caenorhabditis elegans mutations with respect to the domain organization of the proteins, and includes stage-specific RNAseq gene expression data generated by the modENCODE project. The underlying database has been reorganized to facilitate independent updates of the different parts of the database and to allow the addition of novel data sets in the future. The web interface is available under http://genome.sfu.ca/gexplore.

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Section: Datasets: Mutationsmentioning

confidence: 99%

“…elegans genes, 10 and the modENCODE project 11 among other things created new gene expression data sets (Boeck et al submitted). Here we describe the current version of GExplore (version 1.4), which has changed considerably compared to the original version.…”

Section: Introductionmentioning

confidence: 99%

GExplore 1.4: An expanded web interface for queries onCaenorhabditis elegansprotein and gene function

Hutter

Suh

2016

Worm

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“…In sorghum, a few mutated genes have been identified by TILLING based on individual amplicons Blomstedt et al, 2012;Krothapalli et al, 2013). Recent advances in high-throughput next-generation sequencing have made it possible to catalog EMS-induced mutations on a large scale (Thompson et al, 2013;Henry et al, 2014). In rice (Oryza sativa) and wheat (Triticum aestivum), sequencing of captured exons has been used to identify large numbers of mutations from a limited number of mutant plants (Henry et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A Sorghum Mutant Resource as an Efficient Platform for Gene Discovery in Grasses

et al. 2016

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Sorghum (Sorghum bicolor) is a versatile C4 crop and a model for research in family Poaceae. High-quality genome sequence is available for the elite inbred line BTx623, but functional validation of genes remains challenging due to the limited genomic and germplasm resources available for comprehensive analysis of induced mutations. In this study, we generated 6400 pedigreed M4 mutant pools from EMS-mutagenized BTx623 seeds through single-seed descent. Whole-genome sequencing of 256 phenotyped mutant lines revealed >1.8 million canonical EMS-induced mutations, affecting >95% of genes in the sorghum genome. The vast majority (97.5%) of the induced mutations were distinct from natural variations. To demonstrate the utility of the sequenced sorghum mutant resource, we performed reverse genetics to identify eight genes potentially affecting drought tolerance, three of which had allelic mutations and two of which exhibited exact cosegregation with the phenotype of interest. Our results establish that a large-scale resource of sequenced pedigreed mutants provides an efficient platform for functional validation of genes in sorghum, thereby accelerating sorghum breeding. Moreover, findings made in sorghum could be readily translated to other members of the Poaceae via integrated genomics approaches.

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“…3b,c). Apart from null alleles of polq-1, we also tested an allele (generated via random mutagenesis in the C. elegans million mutation project 29 ) that has a mutation in its polymerase domain. A change of an evolutionarily highly conserved proline residue at position 1417 into a serine (P1417S) led to a 50% reduction in the number of deletions at endogenous and transgenic G4 sites, which supports a direct role for the polymerase function of POLQ-1 in the generation of G4 DNA-induced deletions (Supplementary Fig.…”

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confidence: 99%

A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites

et al. 2014

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Genomes contain many sequences that are intrinsically difficult to replicate. Tracts of tandem guanines, for instance, have the potential to adopt stable G-quadruplex structures, which are prone to cause genome alterations. Here we describe G4 DNA-induced mutagenesis in Caenorhabditis elegans and identify a non-canonical DNA break repair mechanism that generates deletions characterized by an extremely narrow size distribution, minimal homology of exactly one nucleotide at the junctions, and by the occasional presence of templated insertions. This typical mutation profile is fully dependent on the A-family polymerase Theta, the absence of which leads to profound loss of sequences surrounding G4 motifs. Theta-mediated end-joining prevails over non-homologous end joining and homologous recombination and prevents genomic havoc at replication fork barriers at the expense of small deletions. G4 DNA-induced deletions also manifest in the genomes of wild isolates of C. elegans, indicating a protective role for this pathway during evolution.

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The million mutation project: A new approach to genetics in Caenorhabditis elegans

Cited by 410 publications

References 64 publications

GExplore 1.4: An expanded web interface for queries onCaenorhabditis elegansprotein and gene function

GExplore 1.4: An expanded web interface for queries onCaenorhabditis elegansprotein and gene function

A Sorghum Mutant Resource as an Efficient Platform for Gene Discovery in Grasses

A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites

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