North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing 2

项目总结/摘要 基因组测序技术的快速发展导致了发现的基因组DNA的急剧增加。 许多罕见疾病的遗传原因，并改变了我们诊断和治疗遗传疾病的能力。 条件特别是，全外显子组测序（WES）已被证明是一种非常成功的诊断方法。 在具有高度遗传异质性的病症的患者中的模态。进行临床 测序探索性研究（CSER）联合会，J.S.的项目，“北卡罗来纳州临床基因组 下一代外显子组测序评估”（NCGENES）解决了临床中的几个关键问题， 外显子组测序的应用，包括在各种临床应用WES时的诊断率 情景、处理次要发现的最佳方法、知情同意程序，以及 患者和家属对基因组信息的反应。部分由于CSER计划的成功， WES已广泛用于临床。然而，在广泛实施之前，付款人需要 被说服，以定期涵盖使用水环境卫生服务;因此，关键问题必须解决， 临床应用目前的更新，NCGENES 2，将提供这一必要的证据基础， 组建一个高度跨学科的团队，进行随机临床试验，研究医疗保健结果， 患者、家庭成员、临床医生和实验室人员之间的沟通。此外，NCGENES 2将 解决这些问题，在传统上处于不利地位的人口，以确保基因组的好处， 医药将惠及尽可能多的人群。NCGENES 2的每个目标都将 解决与临床外显子组的现实世界实施高度相关的具体结果 排序：1）技术和分析结果，2）以患者为中心的结果，3）临床结果，以及4） 社会影响，包括经济影响。最终，NCGENES 2将产生必要的 支持使用WES作为遗传性疾病患者管理标准工具的证据 并使其能够在经历健康差异的人群中实施。

Project Summary/Abstract Rapid development of genome sequencing technology has led to dramatic increases in the discovery of the genetic causes of many rare disorders and has transformed our ability to diagnose and treat genetic conditions. In particular, whole exome sequencing (WES) has proven to be a highly successful diagnostic modality in patients with conditions having a high degree of genetic heterogeneity. As part of the Clinical Sequencing Exploratory Research (CSER) consortium, UNC's project, “North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing” (NCGENES) addressed several key issues in the clinical application of exome sequencing, including the diagnostic yield when applying WES in diverse clinical scenarios, optimal approaches to dealing with secondary findings, the informed consent process, and responses of patients and families to genomic information. Due in part to the success of the CSER program, WES has become widely clinically available. However, before it can be widely implemented payers will need to be convinced to routinely cover the use of WES; thus, critical questions must be addressed regarding its clinical utility. The current renewal, NCGENES 2, will provide this necessary evidence base by bringing together a highly inter-disciplinary team to conduct a randomized clinical trial to study healthcare outcomes and communication among patients, family members, clinicians, and laboratorians. Moreover, NCGENES 2 will address these issues in traditionally disadvantaged populations to ensure that the benefits of genomic medicine will accrue to the broadest possible segment of the population. Each aim of NCGENES 2 will address specific outcomes that are highly relevant to the real-world implementation of clinical exome sequencing: 1) technical and analytic outcomes, 2) patient-centered outcomes, 3) clinical outcomes, and 4) societal outcomes, including economic implications. Ultimately, NCGENES 2 will generate the necessary evidence to support the use of WES as a standard tool in the management of patients with genetic disorders and enable its implementation in populations that experience health disparities.