Lost-of-function variants in the 1000 genomes data set and implications to GWAS

1000 个基因组数据集中的功能丧失变异及其对 GWAS 的影响

基本信息

批准号：
8141451
负责人：
HONGYU ZHAO
金额：
$ 27.07万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-13 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8141451
关键词：
Affect Bioinformatics Cataloging Catalogs Categories Collaborations Communities Complex Data Data Set Databases Development Disabled Persons Disease Disease Association Exons Genes Genetic Genetic Polymorphism Genetic Population Study Genetic Variation Genome Genotype Health Human Human Genetics Individual International Knockout Mice Knowledge Literature Maps Methodology Methods Molecular Molecular Biology Molecular Genetics Molecular Profiling Ontology Phenotype Population Population Genetics Property Proteins RNA Splicing Research Research Personnel Research Proposals Resources Risk Role Sampling Signal Transduction Single Nucleotide Polymorphism Site Statistical Methods Surveys Transcript Variant Work base cost effective experience genetic analysis genetic variant genome sequencing genome wide association study human disease improved insertion/deletion mutation insight loss of function public health relevance tool trait

项目摘要

DESCRIPTION (provided by applicant): The 1000 Genomes Project is an international research consortium whose aim is to produce a detailed map of human genetic variation to support disease studies with major sequencing effort. This project involves sequencing the genomes of at least a thousand people from around the world to facilitate the discovery and understanding of genetic variants such as single nucleotide polymorphisms and structural variants. The data generated from this project will help in the discovery of regions in the genome containing genetic variations associated with risk of human diseases as previously attempted by efforts such as the HapMap Project. However, there are significant challenges in the analysis, annotation, and applications of these data to guide the identifications of variants associated with diseases and various traits. In this application, we will focus on loss-of-function variants because they represent a major class of genetic variations that are potentially involved in complex traits, and we believe a comprehensive characterization of these variants and making the knowledge gained available to the general research community will facilitate the identifications of genes involved in complex traits. To accomplish this objective, we will develop a bioinformatics pipeline to identify loss-of-function variants from the 1000 genome data, associate them with other types of information accumulated in the literature and public databases, such as gene ontology, protein interactions, expression profiles, investigate the best approaches to attain the genotypes of these variants in population samples, and develop statistical methods to incorporate the annotation results to increase the statistical power to identify loss of function variants affecting complex traits. We will disseminate the methods and results to the public both through a stand-alone application focusing of loss of function variants as well as through collaboration with the UCSC Genome Browser team to add tracks on their browser to different types of information on these loss of function variants. We believe that this proposed project will generate very valuable resources to the scientific community that can significantly enhance our understanding of loss of function variants in human populations and use such knowledge to more effectively improve human health. RELEVANCE: The research proposal is developed to generate very valuable resources to the scientific community that can significantly enhance our understanding of loss of function variants in human populations and use such knowledge to more effectively improve human health.

描述（由申请人提供）： 1000个基因组项目是一个国际研究联盟，其目的是制作人类遗传变异的详细图表，以大量的测序努力支持疾病研究。该项目涉及对世界各地至少一千人的基因组进行测序，以促进对遗传变异的发现和理解，例如单核苷酸多态性和结构变异。该项目产生的数据将有助于发现包含与人类疾病风险相关的基因组中的区域，如HAPMAP项目（例如HAPMAP项目）所尝试的。但是，这些数据的分析，注释和应用中存在重大挑战，以指导与疾病和各种特征相关的变体的识别。在此应用程序中，我们将重点关注功能丧失变体，因为它们代表了可能涉及复杂特征的一大批遗传变异，并且我们相信这些变体的全面表征并使一般研究社区获得的知识将促进涉及复杂性状涉及的基因的认同。为了实现这一目标，我们将开发一个生物信息学管道，以确定1000个基因组数据中的功能丧失变异，并将它们与文献和公共数据库中积累的其他类型的信息联系起来，基因本体论，蛋白质相互作用，表达概况，表达概况，表达概况，并研究统计学的统计学方法，以使其在统计学方面融合了统计型号，从而融入了统计学方法，并将其纳入统计型。影响复杂性状的功能变异的丧失。我们将通过独立的应用程序的焦点以及与UCSC基因组浏览器团队的合作，将其浏览器上的轨道添加到有关功能变体丢失的不同类型的信息中，从而将方法和结果传播给公众。我们认为，这个拟议的项目将为科学界创造非常宝贵的资源，这可以显着增强我们对人类人群功能变异的丧失的理解，并利用这种知识来更有效地改善人类健康。相关性：开发了研究建议是为了为科学界创造非常宝贵的资源，这些资源可以显着增强我们对人类人群功能变异的丧失的理解，并利用这种知识来更有效地改善人类健康。