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http://C.Elegans: Mining the functional genomic landscape

Nature Reviews Genetics volume 2, pages 681–689 (2001)Cite this article

Key Points

  • The goals of functional genomics are to speed up genetic analysis and ultimately to facilitate analysis of complex biological phenomena that might not be amenable to classical studies.

  • The C. elegans genome contains 19,717 predicted genes, encoded by 97 Mb and only a fraction of these genes have been studied using classical approaches.

  • Functional genomic approaches aim to provide insights into the function of new worm genes and hopefully will pave the way for functional genomic analysis of the human genome.

  • RNA interference (RNAi) and PCR-based knockouts are the first port of call in gene function studies. All predicted genes are being knocked down in RNAi screens and the results are made available in online searchable databases. The Knockout Consortium plans to knock out all predicted genes and make the knockout strains available to the C. elegans research community.

  • Publically available microarray data is a valuable source of information on gene expression. This growing data set will ultimately be stored in an online database — a part of the Stanford Microarray Database.

  • Large-scale proteomics projects that use modified yeast two-hybrid approaches have just begun and, once validated by additional in vivo data, such as RNAi, or by information from other species, will provide useful information on protein–protein interactions.

Abstract

Caenorhabditis elegans is a powerful animal model for the study of functional genomics. The completed and well-annotated DNA sequence is available and a systematic study of gene function by RNA-interference-mediated knockdown of every gene is in progress. Full-genome DNA microarrays and DNA chips can be used to determine expression changes at different stages of development and in different mutant backgrounds, and a protein-interaction map based on the yeast two-hybrid approach is in progress. These high-capacity approaches to studying gene function will provide new insights into invertebrate and vertebrate biology.

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Figure 1: Annotation of the genome sequence.
Figure 2: RNAi screens in Caenorhabditis elegans.
Figure 3: Gene expression profiles from DNA microarray experiments.

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Author information

Authors and Affiliations

  1. Departments of Developmental Biology and Genetics, Stanford University Medical School, Stanford, 94305, California, USA

    Stuart K. Kim

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  1. Stuart K. Kim
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DATABASE LINKS

WNT

mcm-6

mcm-5

mcm-2

mcm-3

mcm-4

mcm-7

FURTHER INFORMATION

WormPD

WormBase

Intronerator

C.elegansWWW.server

Julie Ahringer

Tony Hyman

UK HGMP Resource Centre

Ken Kemphues

Asako Sugimoto

Genome-wide RNA-interference-based screen for genes important in cell division

Robert Barstead

Donald Moerman

Shohei Mitani

Andrew Hill

Craig Hunter

Affymetrix

Kim lab C. elegans microarray page

Research Genetics

Stanford Microarray Database

The Sanger Centre

Marc Vidal

Knockout Consortium

Glossary

METAZOAN

A multicellular organism.

RAS

A family of proteins that function as signal transducers in the cytoplasm of mammalian and other eukaryotic cells. Constitutively active Ras has been implicated in carcinogenesis.

YEAST TWO-HYBRID APPROACH

A technique used to test if two proteins physically interact with each other. One protein is fused to the GAL4 activation domain and the other to the GAL4 DNA-binding domain, and both fusion proteins are introduced into yeast. Expression of a GAL4-regulated reporter gene indicates that the two proteins physically interact.

DNA MICROARRAY

Array of PCR products (corresponding to either genomic or cDNA sequence) that is deposited onto solid glass slides.

SATURATION GENETIC SCREEN

A genetic screen that is designed to recover at least one mutation in every gene.

DNA CHIP

An array of short DNA oligonucleotides (usually 20 nucleotides long) synthesized onto a solid support by photolithography, each of which corresponds to a single gene. In this method, specific areas of a DNA chip are activated by light, allowing these regions to react with a base on the oligonucleotides, so binding them to the chip.

TRA-1

A zinc-finger transcription factor that is the final target of the sex-determination pathway in Caenorhabditis elegans; its expression leads to hermaphrodite development, whereas lack of its expression leads to male development.

DAUER

Juvenile nematode in which development arrests during unsuitable conditions and then resumes when conditions improve.

RT-PCR

A type of PCR in which RNA is converted into double-stranded DNA, which is then amplified.

SHUTTLE VECTOR

A plasmid into which DNA fragments are cloned and from which they can be re-cloned into various other vectors, such as green fluorescent protein, lacZ or heat-shock vectors.

BAIT

In a yeast two-hybrid approach, this is the protein that is fused to the GAL4 DNA-binding domain.

FORWARD GENETIC SCREEN

A genetic screen in which mutants are isolated on the basis of their phenotype and the responsible gene is identified by positional cloning or by a candidate-gene approach.

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Kim, S. http://C.Elegans: Mining the functional genomic landscape. Nat Rev Genet 2, 681–689 (2001). https://doi.org/10.1038/35088523

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