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The versatile worm: genetic and genomic resources for Caenorhabditis elegans research

Key Points

  • Several major biological discoveries have been made by Caenorhabditis elegans researchers over the years. Today, C. elegans remains one of the most versatile and exciting model organisms to study.

  • Although the extensive palette of tools and resources developed by the C. elegans community greatly facilitates new discoveries, it can also be overwhelming to new worm biologists.

  • Here we discuss the main resources that have been developed for C. elegans research with the aim of helping newcomers to the field in selecting the tools that are best suited to their needs. We also hope that this article will become a useful reference for established C. elegans scientists.

  • We first describe C. elegans online databases and resources that cover topics ranging from worm anatomy to phenotypes and gene function, to information on related nematodes and comparative genomics. They also include tools that allow the retrieval of expression patterns, automated data extraction from the literature, analysis of microarray data, and so on.

  • We then discuss the experimental resources that are available to the C. elegans community, including collections of genomic and cDNA clones, full-genome RNAi libraries, gene-knockout services, repositories of mutant and transposon-tagged strains, reagents for studies of gene function and expression patterns, vector kits for a variety of C. elegans-specific applications, and so on.

  • Although the importance of the existing resources cannot be overestimated, the continual expansion of C. elegans research will require their further improvement, and the development of radically new approaches and tools. We hope that this article will be helpful in identifying new research opportunities and will stimulate the development of additional resources.

Abstract

Since its establishment as a model organism, Caenorhabditis elegans has been an invaluable tool for biological research. An immense spectrum of questions can be addressed using this small nematode, making it one of the most versatile and exciting model organisms. Although the many tools and resources developed by the C. elegans community greatly facilitate new discoveries, they can also overwhelm newcomers to the field. This Review aims to familiarize new worm researchers with the main resources, and help them to select the tools that are best suited for their needs. We also hope that it will be helpful in identifying new research opportunities and will promote the development of additional resources.

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Figure 1: WormAtlas.
Figure 2: WormBase Genome Browser.
Figure 3: PhenoBank report page.
Figure 4: n-Browse interaction viewer.
Figure 5: NEXTDB map view.

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Acknowledgements

We thank G. Schindelman for helpful discussions and assistance. I.A. is supported by a grant to WormBase from the US National Human Genome Research Institute (P41-HG02223). P.W.S. is an investigator with the Howard Hughes Medical Institute, Pasadena, USA.

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Correspondence to Igor Antoshechkin.

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Glossary

Controlled vocabulary

In contrast to natural language vocabularies, which have no restrictions on the terms that can be used, controlled vocabulary is a set of predefined, authorized terms that have been chosen by its designer to reduce the inherent ambiguity in human language and ensure consistency of concept descriptions.

Gateway recombinational cloning

Gateway cloning technology is based on the site-specific recombination system of λ phage, which allows rapid transfer of DNA fragments between different vectors while maintaining the correct orientation and reading frame. It provides a highly efficient alternative to the restriction-enzyme and ligase-based cloning strategy.

Expression topomap

Expression topomap is a visualization of genes that show correlated expression across a large set of microarray experiments. Co-regulated genes appear as mountains, the height of which indicates local gene density. Expression topomap can be used to infer gene functions or to identify genes that are co-regulated with known sets of genes.

Ontology

Like controlled vocabularies, ontologies, as used in computer science, describe objects using predefined terms. In addition, ontologies define relationships between objects, making it possible to capture the structure of a set of objects.

Synthetic phenotype

A phenotype that is produced when two or more mutations that have no discernable phenotypes on their own are combined.

MosTIC

(Mos1 excision-induced transgene-instructed gene conversion). In MosTIC experiments, a double-strand break (DSB) is introduced by excision of the Mos1 transposable element, which is then repaired using a transgene containing sequences that are homologous to the DSB flanking regions as a template. Modifications that are present in the transgene are incorporated into the genome to enable efficient genome engineering.

Comparative genomic hybridization

Comparative genomic hybridization measures differences in DNA copy numbers between two genomes, usually between a reference and a sample genome. This method can be used to detect deletions, duplications and translocations, and to map associated breakpoints with unprecedented precision and speed.

ChIP-on-Chip

ChIP-on-Chip combines chromatin immunoprecipitation (ChIP) with microarray analysis, most commonly using uniform tiling arrays that cover the whole genome or chips that focus on known promoter regions. ChIP-on-Chip allows the rapid identification of binding sites of DNA-binding proteins, such as transcription factors and histones.

Smg-dependent control of gene expression

mRNAs containing premature stop codons are rapidly degraded by the nonsense-mediated decay pathway, which in C. elegans is represented by members of the Smg gene family. This makes it possible to control the expression of transgenes carrying aberrant 3′ UTRs by regulating the Smg-pathway activity, for example, by using a temperature-sensitive allele of smg-1.

Polony-based DNA sequencing

Polonies (polymerase colonies) are created either on a surface such as a slide or gel, or in emulsion attached to beads. PCR within each polony produces clusters that contain millions of template copies, which grow like bacterial colonies. The amplified template can then be sequenced by synthesis or ligation in a highly parallel fashion, enabling high-throughput genome sequencing.

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Antoshechkin, I., Sternberg, P. The versatile worm: genetic and genomic resources for Caenorhabditis elegans research. Nat Rev Genet 8, 518–532 (2007). https://doi.org/10.1038/nrg2105

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