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Science,
1998]
The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is a variety of repeated sequences, both local and dispersed. The distinctive distribution of some repeats and highly conserved genes provides evidence for a regional organization of the chromosomes.
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Annu Rev Genomics Hum Genet,
2015]
The modENCODE (Model Organism Encyclopedia of DNA Elements) Consortium aimed to map functional elements-including transcripts, chromatin marks, regulatory factor binding sites, and origins of DNA replication-in the model organisms Drosophila melanogaster and Caenorhabditis elegans. During its five-year span, the consortium conducted more than 2,000 genome-wide assays in developmentally staged animals, dissected tissues, and homogeneous cell lines. Analysis of these data sets provided foundational insights into genome, epigenome, and transcriptome structure and the evolutionary turnover of regulatory pathways. These studies facilitated a comparative analysis with similar data types produced by the ENCODE Consortium for human cells. Genome organization differs drastically in these distant species, and yet quantitative relationships among chromatin state, transcription, and cotranscriptional RNA processing are deeply conserved. Of the many biological discoveries of the modENCODE Consortium, we highlight insights that emerged from integrative studies. We focus on operational and scientific lessons that may aid future projects of similar scale or aims in other, emerging model systems.
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Cell,
2001]
In 1998, The C. elegans Sequencing Consortium (1998) announced the essentially complete Caenorhabditis elegans genomic sequence, setting a high standard for sequencing multicellular genomes. As of April 2001, the C. elegans genome, including repetitive regions, is >99.6% complete with sequence equivalent to what many genome projects call phase III. How has this changed the lives of C. elegans researchers, and our view of the worm?
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Autophagy,
2024]
Professor Richard (Rick) Morimoto is the Bill and Gayle Cook Professor of Biology and Director of the Rice Institute for Biomedical Research at Northwestern University. He has made foundational contributions to our understanding of how cells respond to various stresses, and the role played in those responses by chaperones. Working across a variety of experimental models, from <i>C</i>. <i>elegans</i> to human neuronal cells, he has identified a number of important molecular components that sense and respond to stress, and he has dissected how stress alters cellular and organismal physiology. Together with colleagues, Professor Morimoto has coined the term "proteostasis" to signify the homeostatic control of protein expression and function, and in recent years he has been one of the leaders of a consortium trying to understand proteostasis in healthy and disease states. I took the opportunity to talk with Professor Morimoto about proteostasis in general, the aims of the consortium, and how autophagy is playing an important role in their research effort.
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Methods Mol Biol,
2006]
The methods used by the Caenorhabditis elegans Gene Knockout Consortium are conceptually simple. One does a chemical mutagenesis of wild-type C. elegans, and then screens the progeny of the mutagenized animals, in small mixed groups, using polymerase chain reaction (PCR) to identify populations with animals where a portion of DNA bounded by the PCR primers has been deleted. Animals from such populations are then selected and grown clonally to recover a pure genetic strain. We categorize the steps needed to do this as follows: (1) mutagenesis and DNA template preparation, (2) PCR detection of deletions, (3) sibling selection, and (4) deletion stabilization. These are discussed in detail in this chapter.
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Genome Res,
1995]
Caenorhabditis elegans, a free-living nematode worm, has proved a particularly useful model organism for studying the anatomy, behavior, genetics, and development of a metazoan. It also has one of the smallest genomes of the higher eukaryotes (100 Mb distributed over six chromosomes), making it an ideal candidate for detailed molecular analysis. The C. elegans genome project began over 10 years ago and is a collaberative effort between two laboratories (St. Louis, MO, USA and Cambridge, UK), with the ultimate aim of mapping and sequencing the whole of the 100-Mb genome. The consortium has now completed the sequence of approximately one-fifth of the genome and plans to have sequenced more than half the genome before the end
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Brief Funct Genomic Proteomic,
2008]
The combined efforts of the Caenorhabditis elegans Knockout Consortium and individuals within the worm community are moving us closer to the goal of identifying mutations in every gene in the nematode C. elegans. At present, we count about 7000 deletion alleles that fall within 5500 genes. The principal method used to detect deletion mutations in the nematode utilizes polymerase chain reaction (PCR). More recently, the Moerman group has incorporated array comparative genome hybridization (aCGH) to detect deletions across the entire coding genome. Other methods used to detect mutant alleles in C. elegans include targeting induced local lesion in genomes (TILLING), transposon tagging, using either Tc1 or Mos1 and resequencing. These combined strategies have improved the overall throughput of the gene-knockout labs, and have broadened the types of mutations that we, and others, can identify. In this review, we will discuss these different approaches.
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Genetica,
2009]
The nematode Caenorhabditis elegans is a widely appreciated, powerful platform in which to study important biological mechanisms related to human health. More than 65% of human disease genes have homologues in the C. elegans genome, and essential aspects of mammalian cell biology, neurobiology and development are faithfully recapitulated in this organism. The EU-funded NemaGENETAG project was initiated with the aim to develop cutting-edge tools and resources that will facilitate modelling of human pathologies in C. elegans, and advance our understanding of animal development and physiology. The main objective of the project involves the generation and evaluation of a large collection of transposon-tagged mutants. In the process of achieving this objective the NemaGENETAG consortium also endeavours to optimize and automate existing transposon-mediated mutagenesis methodologies based on the Mos1 transposable element, in addition to developing alternatives using other transposon systems. The final product of this initiative-a comprehensive collection of transposon-tagged alleles-together with the acquisition of efficient transposon-based tools for mutagenesis and transgenesis in C. elegans, should yield a wealth of information on gene function, immediately relevant to key biological processes and to pharmaceutical research and development.