Clinical Sequencing Core Facility for the Undiagnosed Diseases Network

描述（由申请人提供）：该项目的目标是通过创建一个测序核心设施，为网络提供外显子组和基因组测序，以支持未诊断疾病计划的目标。校外机会“未诊断疾病网络的临床站点”将创建一个机构联盟，该联盟将建立共同的协议，以改善患者获得最先进的诊断方法，并促进诊断和治疗这些患者的发现和创新。对这一协调努力很重要的是使用共同的诊断模式，以便各地点之间能够随时分享数据。因此，已经提出了指定一个单一的测序核心设施，该设施将为网络提供最先进的外显子组和基因组测序。贝勒全基因组实验室（WGL）是人类基因组测序中心和贝勒分子和人类遗传学系的合作成果，它融合了这两个领域的具体专业知识。WGL是CAP和CLIA认证的实验室，开发了外显子组测序作为其第一个测试。自2011年10月临床外显子组测序服务开始以来，WGL已经为2000多名患者进行了测序、分析并提供了外显子组测序的最终临床报告，其中约26%的病例接受了分子诊断。因此，Baylor WGL非常适合通过扩展我们的计划以作为测序核心来加入网络。为了响应RFA的指示，我们将对先证者和家庭成员进行外显子组测序，并在两周内向网络提供原始序列读数和质量控制指标。认识到不同临床研究中心的需求和经验可能不同，我们提出了额外的序列分析和下游序列结果解释的替代方案。这些选择包括线粒体DNA测序;第一层自动化临床解释， 我们的基因组实验室主任可以通过咨询的方式对基因组变异进行全面的临床解释。此外，我们提出了全基因组测序的选择。指导委员会可以权衡这些选择，为参加该计划的患者提供最有效和最具成本效益的分子诊断途径。

DESCRIPTION (provided by applicant): The objectives of this project are to support the goals of the Undiagnosed Diseases Program by creating a sequencing core facility to provide exome and genome sequencing for the network. The extramural opportunity "Clinical Sites for an Undiagnosed Diseases Network" will create a consortium of institutions that will build common protocols to improve patient access to state-of-the-art diagnostic methods, and to promote discovery and innovation in diagnosing and treating these 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 designation of a single sequencing core facility that will provide state-o-the-art exome and genome sequencing for the network has been proposed. The Baylor Whole Genome Laboratory (WGL) is a collaborative effort of the Human Genome Sequencing Center and the Department of Molecular and Human Genetics at Baylor, which merges the specific expertise of both areas. The WGL is a CAP and CLIA certified laboratory that developed exome sequencing as its first test. Since the beginning of the clinical exome sequencing service in October 2011, the WGL has sequenced, analyzed, and provided final clinical reports of exome sequencing for over 2000 patients with approximately 26% of cases receiving a molecular diagnosis. Therefore, the Baylor WGL is well suited to join the network by expanding our program to serve as the sequencing core. In response to the directives of the RFA, we will perform exome sequencing for probands and family members and deliver raw sequence reads and quality control metrics to the network within a two week period. Recognizing that the needs and experience of the various clinical sites may differ, we propose alternatives for additional sequence analysis and downstream interpretation of sequence results. These options include mitochondrial DNA sequencing; a first tier automated clinical interpretation with prioritization of variants, and an option for a full clinical interpretation in a consultative fashion with our ABMG-certified Whole Genome laboratory directors. In addition, we propose the option of whole genome sequencing. These 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.