UCLA clinical site for the investigation of undiagnosed disorders

加州大学洛杉矶分校临床中心，用于调查未确诊疾病

基本信息

批准号：
8686203
负责人：
Katrina M Dipple
金额：
$ 80万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8686203
关键词：
Address Affect Basic Science Biochemical Bioinformatics Caring Cellular biology Clinic Clinical Clinical Management Clinical Research Clinical Sciences Clinical Trials Communication Complex Consent County DNA Data Data Collection Development Diagnosis Diagnostic Disclosure Disease Disease Management Elements Ensure Etiology Family Family member Foundations Genes Genetic Genetic Counseling Genome Genomics Goals Health Health Personnel Healthcare Healthcare Systems Hereditary Disease Human Genome Individual Institutes Investigation Laboratories Link Los Angeles Medical Genetics Medicine Modeling Mutation Outcome Patient Selection Patients Persons Phenotype Physicians Population Process Rare Diseases Recommendation Registries Reporting Research Research Infrastructure Research Personnel Resources Site Source Standardization Symptoms System Systems Analysis Taxes Technology Testing Time Translating Translational Research Translations Underinsured United States Variant Visit Work base clinical care clinical phenotype clinical practice clinical research site clinically relevant design exome exome sequencing experience follow-up gene function genetic variant health care delivery improved medical specialties methylome network models new technology non-genomic patient registry psychosocial public health relevance rare variant research clinical testing socioeconomics

项目摘要

DESCRIPTION (provided by applicant): Undiagnosed diseases take a disproportionate toll on the health care system and on affected patients and families. Our proposal builds a collaborative network of researchers and healthcare providers, all with a stake in improving healthcare and outcomes for persons affected by various rare genetic disorders. Our approach will synergize basic and clinical research with the use of cutting-edge phenotyping technologies, an array of world class experts, and the translation of whole exome sequencing to the bedside. This will result in the development of a diagnostic process, rapidly translating clinical evidence into improved healthcare delivery. The Undiagnosed Disease Network (UDN) will provide the foundation to stimulate additional multi-and interdisciplinary basic, translational, and clinical research. Investigating rare diseases involving multiple systems and incorporating comprehensive genomic data into clinical care creates considerable challenges, from the interpretation of vast amounts of genetic variants to their relevance to the symptoms, to the communication issues linked to their disclosure, and to their impact on clinical management. Our proposal delivers a platform for a UDN Clinical Site that functions locally and as part of a network to tackle the incorporation of genomic information into the clinical workflow, analyze patients' symptoms in a standardized and reproducible fashion, and perform research investigations to elucidate further the mechanisms of undiagnosed diseases. We will reach these overarching goals by implementing the following specific aims: Aim 1: Create a UDN clinic model that functions locally and network-wide Aim 2: Investigate the clinical phenotypes of new and rare disorders Aim 3: Investigate the underlying mechanisms of new and rare disorders Aim 4: Build a network-wide sustainable infrastructure for translational research on new and rare disorders Our project integrates the resources of (1) the infrastructure of a Clinical and Translational Science Institute, allowing for a state-of-the-art clinical investigation of complex, multisystemic disorders, within a maximum of a week stay; (2) an experienced, team of clinicians from all specialty fields, that delivers clinical use of whole- exome sequencing, and it integration in the diagnostic process of rare, undiagnosed disorders; (3) the UCLA Clinical Genomic Center that offers bioinformatics data handling, and clinical laboratory exome sequencing, that will interpret and report clinically relevant DNA variants; (4) expertise in the investigation of environmental effects on clinical symptoms; (5) a registry infrastructure with longstanding experience in standardization of phenotypic and genotypic information; (6) access to a large, ethnically varied population and (7) a sustainable approach, with provisions to care for un/underinsured patients. Overall, our approach is designed to work cooperatively with the other Clinical Sites, the Coordinating Center, and the IRP-UDP, by capitalizing on our experiences in medical genetics, genetic counseling, clinical exome sequencing, and statistical genomics.

描述（由申请人提供）：未诊断的疾病对医疗保健系统以及受影响的患者和家庭造成不成比例的损失。我们的建议建立了一个由研究人员和医疗保健提供者组成的协作网络，所有这些都在改善受各种罕见遗传疾病影响的人的医疗保健和成果方面的利益。我们的方法将使用尖端的表型技术，一系列世界一流的专家以及整个外显子组测序到床边的翻译来协同基础和临床研究。这将导致诊断过程的发展，将临床证据迅速转化为改善的医疗保健。未诊断的疾病网络（UDN）将为刺激额外的多学科基础，转化和临床研究提供基础。调查涉及多种系统并将全面基因组数据纳入临床护理的罕见疾病，从对大量遗传变异的解释到与症状的相关性，到与其披露有关的沟通问题以及对临床管理的影响。我们的建议为UDN临床部位提供了一个平台，该站点在本地起作用，也是网络的一部分，以应对将基因组信息纳入临床工作流程中，以标准化和可重复的方式分析患者的症状，并进行研究调查以进一步阐明未诊断疾病的机制。 We will reach these overarching goals by implementing the following specific aims: Aim 1: Create a UDN clinic model that functions locally and network-wide Aim 2: Investigate the clinical phenotypes of new and rare disorders Aim 3: Investigate the underlying mechanisms of new and rare disorders Aim 4: Build a network-wide sustainable infrastructure for translational research on new and rare disorders Our project integrates the resources of (1) the infrastructure of a临床和转化科学研究所，允许对复杂的最新临床研究，多系统性疾病，最多一周内；（2）一支来自所有专业领域的经验丰富的临床医生团队，可在稀有，未诊断的疾病的诊断过程中进行全外显子组测序的临床使用；（3）提供生物信息学数据处理和临床实验室外显子组测序的UCLA临床基因组中心，该中心将解释和报告与临床相关的DNA变体；（4）研究环境对临床症状的影响的专业知识；（5）在表型和基因型信息标准化方面具有长期经验的注册基础设施；（6）进入大型，种族多样化的人口，（7）一种可持续的方法，并提供了照顾未保险患者的规定。总体而言，我们的方法旨在通过利用我们在医学遗传学，遗传咨询，临床外显子组测序和统计基因组学方面的经验来与其他临床站点，协调中心和IRP-IDP合作合作。