UW Center for Mendelian Genomics

威斯康星大学孟德尔基因组学中心

基本信息

批准号：
8393219
负责人：
MICHAEL Joseph BAMSHAD
金额：
$ 490.04万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-05 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8393219
关键词：
Affect Biological Candidate Disease Gene Chromosome Mapping Clinical Code Collaborations Communities Complex Coupling DNA DNA Sequence Data Databases Deposition Development Diagnosis Disease Employee Strikes Ensure Equilibrium Exhibits Family Functional disorder Gene Mutation Genes Genetic Genome Genomics Goals Hereditary Disease Human Biology Human Genome Human Genome Project Individual Inheritance Patterns Investigation Leadership Link Medical Genetics Methods Molecular Online Systems Open Reading Frames Pathway Analysis Process Production Protocols documentation Rare Diseases Reporting Research Research Design Research Personnel Resources Role Sampling Sequence Analysis Technology Universities Variant Washington Work analytical method base biobank cost data sharing database of Genotypes and Phenotypes disease-causing mutation exome exome sequencing genetic linkage analysis genome analysis genome sequencing genome-wide human disease improved innovation insight new technology next generation positional cloning programs public health relevance repository success

项目摘要

DESCRIPTION (provided by applicant): Over the past three decades, the genes underlying nearly 3,000 Mendelian disorders have been identified by methods such as linkage analysis and positional cloning. Although the availability of a reference human genome greatly accelerated these efforts, there are thousands of additional suspected Mendelian disorders that remain unsolved. An understanding of the genetic basis of a Mendelian disorder can yield fundamental insights into basic human biology and disease pathophysiology, as well as a molecular basis for diagnosis or carrier status determination. In some instances, biological insights from studying Mendelian disorders can prove highly relevant to our understanding of more common diseases. Recently, we and others have shown that the coupling of targeted capture and next-generation DNA sequencing technology can be used to cost-effectively determine nearly all coding variation in an individual human genome, a process termed exome sequencing. We, and others, have also demonstrated how exome sequencing can be applied to efficiently identify the causal genes for Mendelian disorders that have proven intractable to conventional modes of analysis. To accelerate progress towards a comprehensive understanding of the genetic basis of all Mendelian disorders, we propose to establish the UW Center for Mendelian Genomics. Our proposal has four specific aims: (1) To organize samples for all unsolved Mendelian disorders from investigators around the world, either by their submission to our center for sequencing, or by their inclusion on a public sample list that we will develop; (2) To apply our existing production pipeline for exome and genome sequencing to samples corresponding to unsolved Mendelian disorders, and to improve this process through ongoing technology innovation; (3) To determine the genetic basis for as many unsolved Mendelian disorders as possible, through efficient study design and effective, innovative analysis; (4) To take a leadership role in the dissemination of methods and data.

描述（由申请人提供）：在过去的三十年中，通过连锁分析和位置克隆等方法已经鉴定了近 3,000 种孟德尔疾病的基因。尽管参考人类基因组的出现极大地加速了这些努力，但还有数千种疑似孟德尔疾病仍未得到解决。了解孟德尔疾病的遗传基础可以产生对基本人类生物学和疾病病理生理学的基本见解，以及诊断或携带者状态确定的分子基础。在某些情况下，研究孟德尔疾病的生物学见解可能与我们对更常见疾病的理解高度相关。最近，我们和其他人已经证明，靶向捕获和下一代 DNA 测序技术的结合可用于经济高效地确定单个人类基因组中的几乎所有编码变异，这一过程称为外显子组测序。我们和其他人还证明了如何应用外显子组测序来有效识别孟德尔疾病的致病基因，这些疾病已被证明难以用传统的分析模式解决。为了加速全面了解所有孟德尔疾病的遗传基础，我们建议建立威斯康星大学孟德尔基因组学中心。我们的提案有四个具体目标：（1）组织来自世界各地研究人员的所有未解决的孟德尔疾病的样本，要么将它们提交给我们的中心进行测序，要么将它们纳入我们将开发的公共样本列表中；（2）将我们现有的外显子组和基因组测序生产流程应用于未解决的孟德尔疾病对应的样本，并通过持续的技术创新改进这一流程； (3) 通过高效的研究设计和有效、创新的分析，确定尽可能多的未解决的孟德尔疾病的遗传基础； (4) 在方法和数据传播方面发挥领导作用。