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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：
8597450
负责人：
MICHAEL Joseph BAMSHAD
金额：
$ 498.08万
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/8597450
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 Massive Parallel Sequencing 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 carrier status 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）：在过去三十年中，通过连锁分析和定位克隆等方法鉴定了近3，000种孟德尔疾病的潜在基因。尽管参考人类基因组的可用性大大加速了这些努力，但仍有数千种其他疑似孟德尔疾病尚未解决。了解孟德尔遗传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以证明与我们对更常见疾病的理解高度相关。最近，我们和其他人已经表明，靶向捕获和下一代DNA测序技术的结合可以用于经济有效地确定个体人类基因组中几乎所有的编码变异，这一过程称为外显子组测序。我们和其他人还展示了外显子组测序如何应用于有效地识别孟德尔疾病的致病基因，这些疾病已被证明是传统分析模式难以解决的。为了加速对所有孟德尔疾病的遗传基础的全面了解，我们建议建立孟德尔基因组学UW中心。我们的建议有四个具体目标：（1）组织来自世界各地的研究人员的所有未解决的孟德尔疾病的样本，要么将其提交给我们的测序中心，要么将其列入我们将开发的公共样本列表;（2）将我们现有的外显子组和基因组测序生产管道应用于对应于未解决的孟德尔疾病的样品，并通过持续的技术创新来改善这一过程;（3）通过有效的研究设计和有效的创新分析，确定尽可能多的未解决的孟德尔疾病的遗传基础;（4）在方法和数据的传播中发挥领导作用。