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：线虫秀丽隐杆线虫是生物学中研究最深入的生物体之一。成千上万的科学家利用它来深入了解基本的生物过程，其中许多过程是人类共有的。它的基因组已完全测序，目前已成为多项系统研究的主题，旨在识别基因组的功能元件，并将这些知识整合到对基因组如何指定生物体这一更大问题的理解中。尽管破坏 DNA 序列是探测其功能的最有力方法之一，但在其超过 20,000 个蛋白质编码基因中，仅描述了不到 8,000 个突变，并且几乎没有其他功能元件（包括调控序列）。在秀丽隐杆线虫中发现的 RNAi 提供了另一种改变基因功能的方法，但它有几个重要的局限性，包括有效性可变、需要 RNA 中间体、组织敏感性可变以及缺乏遗传性。现有的突变体不容易在大型系统项目中进行研究；它们存在于各种不同的背景中，其数量之多使处理变得复杂。目前的项目旨在创建一组 2,000 个来自诱变的测序菌株，每个菌株有 500-750 个突变，在标准背景下，这些菌株将很容易被追求特定 DNA 元件功能的研究人员和广泛研究的研究人员使用。影响特定表型的元素的基因组。此外，通过创建大量与表型相关的突变，该集合将为理解更广泛的问题提供一个平台，即不同背景下的不同氨基酸变化如何影响功能。后一个问题至关重要，因为未来几年全基因组和外显子组重测序项目将发现大量人类变异，这将需要一个强大的框架来促进解释。此类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提案的 NHLBI 项目 (RFA-OD-09-004)。 公共卫生相关性：为了充分发挥基因组学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所携带的许多罕见突变的影响。通过生成包含秀丽隐杆线虫基因组中超过 1,000,000 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，从而改进预测。

项目成果

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

百万突变项目：秀丽隐杆线虫遗传学的新方法。

• 发表时间: 2013-10
• 影响因子: 7
• 作者: Thompson, Owen;Edgley, Mark;Strasbourger, Pnina;Flibotte, Stephane;Ewing, Brent;Adair, Ryan;Au, Vinci;Chaudhry, Iasha;Fernando, Lisa;Hutter, Harald;Kieffer, Armelle;Lau, Joanne;Lee, Norris;Miller, Angela;Raymant, Greta;Shen, Bin;Shendure
• 通讯作者: Shendure

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

PhenoMIP：通过分子倒置探针对多种秀丽隐杆线虫种群进行高通量表型分析。

• 发表时间: 2020
• 作者: Mok, Calvin;Belmarez, Gabriella;Edgley, Mark L;Moerman, Donald G;Waterston, Robert H
• 通讯作者: Waterston, Robert H