A genome-wide mutation resource for C. elegans

线虫全基因组突变资源

• 批准号: 7853828
• 负责人: ROBERT H WATERSTON
• 金额: $ 204.26万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-20 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7853828
• 关键词: Affect; Aliquot; Alleles; Amino Acids; Animals; Award; Biological Assay; Biological Process; Biology; British Columbia; Budgets; C. elegans genome; Caenorhabditis; Caenorhabditis elegans; Chemicals; Code; Collection; Communities; Computer software; DNA; DNA Resequencing; DNA Sequence; Data Set; Databases; Dose; Effectiveness; Elements; Essential Genes; Ethylnitrosourea; Exhibits; Freezing; Funding; Generations; Genes; Genetic; Genome; Genomics; Goals; Heritability; Homozygote; Hour; Human; Intermediate Variables; Knowledge; Mutagenesis; Mutagens; Mutation; National Heart, Lung, and Blood Institute; Nematoda; Nonsense Mutation; Organism; Phenotype; Physicians; Proteins; Protocols documentation; Public Health; RNA; RNA Interference; Reading; Research Personnel; Resources; Scientist; Series; Single base substitution; Site; Source; Specific qualifier value; Testing; Tissues; Universities; Untranslated RNA; Variant; exome; falls; gene function; genome-wide; health care delivery; improved; insight; interest; loss of function; mutant; next generation; novel; public health relevance; research study

DESCRIPTION: The nematode C. elegans is one of the most thoroughly studied organisms in biology. It is used by thousands of scientists to gain insight into basic biological processes, many of which are shared with humans. Its genome is fully sequenced and is now the subject of several systematic studies to identify the functional elements of the genome and to integrate this knowledge into an understanding of the larger question of how a genome specifies an organism. Although disruption of DNA sequence is one of the most powerful ways to probe its function, mutations have been described for fewer than 8,000 of its >20,000 protein coding genes and almost none of the other functional elements, including regulatory sequences. RNAi, discovered in C. elegans, provides an alternative means of altering gene function, but it has several important limitations, including variable effectiveness, a requirement for an RNA intermediate, variable tissue sensitivity and a lack of heritability. The available mutants are not readily studied in large systematic projects; they exist in a variety of different backgrounds, and their sheer number complicates handling. The present project aims to create a set of 2,000 sequenced strains derived from mutagenesis, each with 500-750 mutations, in a standard background that will be readily used both by investigators who are pursuing the function of particular DNA elements and by investigators looking broadly across the genome for elements affecting particular phenotypes. In addition, through the creation of a large set of mutations that can be associated with phenotype the collection will provide a platform for understanding the broader question of how different amino acid changes in varying contexts may affect function. This latter question is of key importance, as large numbers of human variants will be discovered in whole genome and exome resequencing projects in the coming years, which will require a strong framework to facilitate interpretation. Such projects include the 1,000 genomes project already underway and the NHLBI project currently soliciting proposals (RFA-OD-09-004). PUBLIC HEALTH RELEVANCE: For genomics to realize its full potential in improving public health and health care delivery, it will be essential for scientists and physicians to be able to predict the effect of the many rare mutations that each of us harbor. By generating a data set of more than 1,000,000 mutations across the C. elegans genome, we will provide a platform that will facilitate the discovery of both direct precedents and general principles that will enable improved predictions.

描述：线虫是生物学中研究最深入的生物之一。数以千计的科学家使用它来洞察基本的生物过程，其中许多过程与人类共享。它的基因组已经完全测序，现在是几项系统研究的主题，目的是确定基因组的功能元素，并将这些知识整合到理解基因组如何指定有机体这一更大的问题上。尽管打乱DNA序列是探索其功能的最有效方法之一，但在ITS&gt；20000个蛋白质编码基因中，只有不到8000个基因发生了突变，几乎没有其他功能元件发生突变，包括调控序列。在线虫中发现的RNAi提供了一种改变基因功能的替代方法，但它有几个重要的限制，包括可变的有效性、对RNA中间体的要求、可变的组织敏感性和缺乏遗传性。现有的突变体不容易在大型系统工程中进行研究；它们存在于各种不同的背景中，而且它们的数量本身就使处理变得复杂。本项目旨在创建一套来自突变的2,000个测序菌株，每个菌株具有500-750个突变，在一个标准背景下，将容易被研究特定DNA元素功能的研究人员和广泛地在基因组中寻找影响特定表型的元素的研究人员使用。此外，通过创建一大组可以与表型相关的突变，该集合将为理解更广泛的问题提供一个平台，即不同背景下不同氨基酸的变化如何影响功能。后一个问题至关重要，因为未来几年将在全基因组和外显子组重新测序项目中发现大量人类变异，这将需要一个强大的框架来促进解释。这些项目包括已经在进行的1,000个基因组项目和目前正在征求建议书的NHLBI项目(RFA-OD-09-004)。 与公共健康相关：基因组学要充分发挥其在改善公共卫生和医疗保健服务方面的潜力，科学家和医生必须能够预测我们每个人都拥有的许多罕见突变的影响。通过生成一个包含线虫基因组100多万个突变的数据集，我们将提供一个平台，促进发现直接先例和一般原则，从而能够改进预测。

项目成果

PhenoMIP: High-Throughput Phenotyping of Diverse Caenorhabditis elegans Populations via Molecular Inversion Probes.

• DOI: 10.1534/g3.120.401656
• 发表时间: 2020-11-05
• 期刊: G3 (Bethesda, Md.)
• 作者: Mok C;Belmarez G;Edgley ML;Moerman DG;Waterston RH
• 通讯作者: Waterston RH

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

• DOI: 10.1101/gr.157651.113
• 发表时间: 2013-10
• 期刊: Genome research
• 影响因子: 7
• 作者: Thompson O;Edgley M;Strasbourger P;Flibotte S;Ewing B;Adair R;Au V;Chaudhry I;Fernando L;Hutter H;Kieffer A;Lau J;Lee N;Miller A;Raymant G;Shen B;Shendure J;Taylor J;Turner EH;Hillier LW;Moerman DG;Waterston RH
• 通讯作者: Waterston RH