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

项目总结/摘要 该项目的目标是通过以下方式支持未诊断疾病网络的目标： 继续我们在第一阶段的工作，作为测序核心设施，提供外显子组和基因组测序 为了电视网。校外机会“未诊断疾病网络的临床网站”创建了一个 建立共同协议以改善患者获得最先进诊断的机构联盟 方法，并促进诊断和治疗患者的发现和创新。重要的是 协调一致的努力是使用共同的诊断模式，以便数据可以很容易地共享， 网站。因此，继续为测序核心设施提供资金， 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 I期项目，对大约50%的UDN进行全外显子组测序 参与者Baylor Genetics是CAP和CLIA认证的实验室，开发了完整的外显子组 2011年10月将测序作为临床试验。贝勒遗传学公司已经测序，分析，并提供了最终的 超过11，000例患者的外显子组测序的临床报告，其中约30-40%的病例接受 分子诊断我们的分子临床解释服务包括16个ABMGG认证的临床 分子遗传学家和四位认证遗传咨询师。到目前为止，在UDN第一阶段，贝勒核心 对256名先证者及其家族成员进行了外显子组测序，共757个外显子。整个 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的指示，我们将对先证者和家族进行外显子组测序 成员（每个先证者3.5人），并将原始序列读数和质量控制指标提供给 网络在两周内，然后是临床报告。此外，Baylor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， 也在2周内沉积原始序列读数。此外，我们提出了RNASeq的选择， 在研究的基础上，对具有非诊断性外显子组或基因组分析的个体进行。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 对参加这个项目的病人进行分子诊断。

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.