Clinical Sequencing Core Facility for the Undiagnosed Diseases Network (UDN)

未确诊疾病网络 (UDN) 的临床测序核心设施

• 批准号: 10205125
• 负责人: Christine Eng
• 金额: $ 95.1万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10205125
• 关键词: Area; CLIA certified; Clinical; Collaborations; Community Networks; Core Facility; DNA Sequencing Facility; DNA sequencing; Data; Deposition; Diagnosis; Diagnostic; Diagnostic Procedure; Dideoxy Chain Termination DNA Sequencing; Disease; Enrollment; Environment; Evaluation; Extramural Activities; Family; Family member; Funding; Genes; Genetic; Genetic Predisposition to Disease; Goals; Individual; Infrastructure; Institution; International; Laboratories; Leadership; Medicine; Modality; Molecular; Molecular Diagnosis; Multiomic Data; Mutation; Participant; Pathway interactions; Patient Care; Patients; Phase; Phenotype; Physicians; Procedures; Protocols documentation; Quality Control; Rare Diseases; Reporting; Research; Research Personnel; Sampling; Secure; Sequence Analysis; Services; Site; Specific qualifier value; Standardization; Syndrome; United States; Update; Validation; Variant; Work; analysis pipeline; causal variant; clinical practice; clinical research site; clinical sequencing; college; cost; cost effective; data integration; exome; exome sequencing; experience; flexibility; gene discovery; genetic counselor; genetic disorder diagnosis; genome analysis; genome sequencing; improved; in silico; innovation; knowledge base; molecular diagnostics; multiple omics; proband; programs; research clinical testing; response; tool; transcriptome sequencing; whole genome

Project Summary/Abstract The objectives of this project are to support the goals of the Undiagnosed Diseases Network (UDN) by continuing our work during Phase I as the sequencing core facility to provide exome and genome sequencing for the network. The extramural opportunity “Clinical Sites for an Undiagnosed Diseases Network” created a consortium of institutions that built common protocols to improve patient access to state-of-the-art diagnostic methods, and to promote discovery and innovation in diagnosing and treating patients. Important to this coordinated effort is the use of common diagnostic modalities such that data can be readily shared among the sites. Therefore, the continued funding of a sequencing core facility that will provide state-of-the-art exome and genome sequencing for the network has been proposed. Baylor College of Medicine and the Baylor Genetics laboratory was selected as one of two sequencing cores for the UDN Phase I project performing whole exome sequencing for approximately 50% of the UDN participants. Baylor Genetics is a CAP and CLIA certified laboratory that developed whole exome sequencing as a clinical test in October 2011. Baylor Genetics has sequenced, analyzed, and provided final clinical reports of exome sequencing for over 11,000 patients with approximately 30-40% of cases receiving a molecular diagnosis. Our molecular clinical interpretation service comprises 16 ABMGG certified clinical molecular geneticists and four certified genetic counselors. To date, during UDN Phase I, the Baylor core performed exome sequencing for 256 probands and their family members for a total of 757 exomes. Whole exome sequencing comprised approximately 36% of the diagnoses made during UDN Phase I for patients and family members In response to the directives of the RFA, we will perform exome sequencing for probands and family members (3.5 individuals per proband) and deliver raw sequence reads and quality control metrics to the network within a two-week period followed by a clinical report. In addition, the Baylor core is now able to offer whole genome sequencing, analysis and clinical reporting in our CAP and CLIA certified laboratory, also with deposition of raw sequence reads within 2 weeks. In addition, we propose the option of RNASeq on a research basis for individuals with a non-diagnostic exome or genome analysis. These sequencing options can be weighed by the Steering Committee to provide the most efficient and cost-effective pathway to a molecular diagnosis for patients enrolled in this program.

项目概要/摘要 该项目的目标是通过以下方式支持未确诊疾病网络 (UDN) 的目标： 在第一阶段继续我们的工作，作为测序核心设施，提供外显子组和基因组测序 对于网络。校外机会“未确诊疾病网络的临床站点”创造了 建立通用协议以改善患者获得最先进诊断的机会的机构联盟 方法，并促进诊断和治疗患者的发现和创新。对此很重要 协调一致的努力是使用共同的诊断模式，以便数据可以在 网站。因此，持续资助测序核心设施将提供最先进的 已经提出了用于网络的外显子组和基因组测序。 贝勒医学院和贝勒遗传学实验室被选为两个测序核心之一 对于 UDN 一期项目，对约 50% 的 UDN 进行全外显子组测序 参与者。 Baylor Genetics 是一家经过 CAP 和 CLIA 认证的实验室，开发了全外显子组 2011 年 10 月将测序作为临床测试。Baylor Genetics 已进行测序、分析并提供最终结果 超过 11,000 名患者的外显子组测序临床报告，其中约 30-40% 的病例接受了 分子诊断。我们的分子临床解读服务包括 16 个 ABMGG 认证的临床 分子遗传学家和四名经过认证的遗传咨询师。迄今为止，在 UDN 第一阶段，贝勒核心 对 256 个先证者及其家庭成员进行了外显子组测序，总共 757 个外显子组。所有的 外显子组测序约占 UDN I 期患者诊断的 36% 和家庭成员 为了响应 RFA 的指令，我们将为先证者及其家人进行外显子组测序 成员（每个先证者 3.5 个人）并向 两周内发布网络，然后提供临床报告。此外，贝勒核心现在能够 在我们的 CAP 和 CLIA 认证实验室提供全基因组测序、分析和临床报告， 还可以在两周内沉积原始序列读数。此外，我们建议选择 RNASeq 基于对具有非诊断性外显子组或基因组分析的个体的研究基础。这些测序 指导委员会可以权衡各种选择，以提供最有效和最具成本效益的途径 为参加该计划的患者进行分子诊断。