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Systematic functional analysis of the Caenorhabditis elegans genome using RNAi

Author

Listed:
  • Ravi S. Kamath

    (University of Cambridge)

  • Andrew G. Fraser

    (University of Cambridge
    Wellcome Trust Sanger Institute)

  • Yan Dong

    (University of Cambridge)

  • Gino Poulin

    (University of Cambridge)

  • Richard Durbin

    (Wellcome Trust Sanger Institute)

  • Monica Gotta

    (University of Cambridge
    Institute of Biochemistry ETH Hoenggerberg)

  • Alexander Kanapin

    (EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus)

  • Nathalie Le Bot

    (University of Cambridge)

  • Sergio Moreno

    (University of Cambridge
    Centro de Investigacion del Cancer, CSIC / Univ. Salamanca, Campus Miguel de Unamuno)

  • Marc Sohrmann

    (Wellcome Trust Sanger Institute
    Institute of Biochemistry ETH Hoenggerberg)

  • David P. Welchman

    (University of Cambridge)

  • Peder Zipperlen

    (University of Cambridge)

  • Julie Ahringer

    (University of Cambridge)

Abstract

A principal challenge currently facing biologists is how to connect the complete DNA sequence of an organism to its development and behaviour. Large-scale targeted-deletions have been successful in defining gene functions in the single-celled yeast Saccharomyces cerevisiae, but comparable analyses have yet to be performed in an animal. Here we describe the use of RNA interference to inhibit the function of ∼86% of the 19,427 predicted genes of C. elegans. We identified mutant phenotypes for 1,722 genes, about two-thirds of which were not previously associated with a phenotype. We find that genes of similar functions are clustered in distinct, multi-megabase regions of individual chromosomes; genes in these regions tend to share transcriptional profiles. Our resulting data set and reusable RNAi library of 16,757 bacterial clones will facilitate systematic analyses of the connections among gene sequence, chromosomal location and gene function in C. elegans.

Suggested Citation

  • Ravi S. Kamath & Andrew G. Fraser & Yan Dong & Gino Poulin & Richard Durbin & Monica Gotta & Alexander Kanapin & Nathalie Le Bot & Sergio Moreno & Marc Sohrmann & David P. Welchman & Peder Zipperlen &, 2003. "Systematic functional analysis of the Caenorhabditis elegans genome using RNAi," Nature, Nature, vol. 421(6920), pages 231-237, January.
    • Handle: RePEc:nat:nature:v:421:y:2003:i:6920:d:10.1038_nature01278
    DOI: 10.1038/nature01278
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    Cited by:

    1. Maria E Gallegos & Sanjeev Balakrishnan & Priya Chandramouli & Shaily Arora & Aruna Azameera & Anitha Babushekar & Emilee Bargoma & Abdulmalik Bokhari & Siva Kumari Chava & Pranti Das & Meetali Desai , 2012. "The C. elegans Rab Family: Identification, Classification and Toolkit Construction," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-19, November.
    2. Mustafa C. Camur & Thomas Sharkey & Chrysafis Vogiatzis, 2022. "The Star Degree Centrality Problem: A Decomposition Approach," INFORMS Journal on Computing, INFORMS, vol. 34(1), pages 93-112, January.
    3. Klement Stojanovski & Ioana Gheorghe & Peter Lenart & Anne Lanjuin & William B. Mair & Benjamin D. Towbin, 2023. "Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Christina Rou Hsu & Gaganpreet Sangha & Wayne Fan & Joey Zheng & Kenji Sugioka, 2023. "Contractile ring mechanosensation and its anillin-dependent tuning during early embryogenesis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Jin-Hyuck Jeong & Jun-Seok Han & Youngae Jung & Seung-Min Lee & So-Hyun Park & Mooncheol Park & Min-Gi Shin & Nami Kim & Mi Sun Kang & Seokho Kim & Kwang-Pyo Lee & Ki-Sun Kwon & Chun-A. Kim & Yong Ryo, 2023. "A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Ichiro Kawasaki & Kenta Sugiura & Taeko Sasaki & Noriyuki Matsuda & Miyuki Sato & Ken Sato, 2024. "MARC-3, a membrane-associated ubiquitin ligase, is required for fast polyspermy block in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Hope Dang & Raul Castro-Portuguez & Luis Espejo & Grant Backer & Samuel Freitas & Erica Spence & Jeremy Meyers & Karissa Shuck & Emily A. Gardea & Leah M. Chang & Jonah Balsa & Niall Thorns & Caroline, 2023. "On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Kevin Y Yip & Roger P Alexander & Koon-Kiu Yan & Mark Gerstein, 2010. "Improved Reconstruction of In Silico Gene Regulatory Networks by Integrating Knockout and Perturbation Data," PLOS ONE, Public Library of Science, vol. 5(1), pages 1-9, January.
    9. Arles Urrutia & Víctor A García-Angulo & Andrés Fuentes & Mauricio Caneo & Marcela Legüe & Sebastián Urquiza & Scarlett E Delgado & Juan Ugalde & Paula Burdisso & Andrea Calixto, 2020. "Bacterially produced metabolites protect C. elegans neurons from degeneration," PLOS Biology, Public Library of Science, vol. 18(3), pages 1-31, March.
    10. Martin Ackermann & Lin Chao, 2006. "DNA Sequences Shaped by Selection for Stability," PLOS Genetics, Public Library of Science, vol. 2(2), pages 1-7, February.
    11. Eleonora Khabirova & Aileen Moloney & Stefan J Marciniak & Julie Williams & David A Lomas & Stephen G Oliver & Giorgio Favrin & David B Sattelle & Damian C Crowther, 2014. "The TRiC/CCT Chaperone Is Implicated in Alzheimer's Disease Based on Patient GWAS and an RNAi Screen in Aβ-Expressing Caenorhabditis elegans," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-13, July.
    12. Svenia D. Heinze & Simon Berger & Stefanie Engleitner & Michael Daube & Alex Hajnal, 2023. "Prolonging somatic cell proliferation through constitutive hox gene expression in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Fanrui Hao & Huimin Liu & Bin Qi, 2024. "Bacterial peptidoglycan acts as a digestive signal mediating host adaptation to diverse food resources in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Malaguti, Giulia & Singh, Param Priya & Isambert, Hervé, 2014. "On the retention of gene duplicates prone to dominant deleterious mutations," Theoretical Population Biology, Elsevier, vol. 93(C), pages 38-51.
    15. Chrysafis Vogiatzis & Mustafa Can Camur, 2019. "Identification of Essential Proteins Using Induced Stars in Protein–Protein Interaction Networks," INFORMS Journal on Computing, INFORMS, vol. 31(4), pages 703-718, October.
    16. Saeid Rasti & Chrysafis Vogiatzis, 2019. "A survey of computational methods in protein–protein interaction networks," Annals of Operations Research, Springer, vol. 276(1), pages 35-87, May.
    17. Wei Cao & Qi Fan & Gemmarie Amparado & Dean Begic & Rasoul Godini & Sandeep Gopal & Roger Pocock, 2024. "A nucleic acid binding protein map of germline regulation in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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