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

通过下一代外显子组测序进行北卡罗来纳州临床基因组评估 2

• 批准号: 10362100
• 负责人: JONATHAN S BERG
• 金额: $ 172.87万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-05 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362100
• 关键词: Address; Clinical; Clinical Data; Communication; Communities; Copy Number Polymorphism; Coupled; Data Collection; Development; Diagnosis; Diagnostic; Differential Diagnosis; Enrollment; Ensure; Evaluation; Family; Family member; Fostering; Genetic; Genetic Diseases; Genetic Heterogeneity; Genomic medicine; Genomics; Geography; Grant; Health Care Costs; Healthcare; Healthcare Systems; Informed Consent; Intervention; Massive Parallel Sequencing; Medical; Minority Groups; Modality; Modeling; Molecular Analysis; Molecular Diagnosis; North Carolina; Outcome; Participant; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Pattern; Performance; Personal Satisfaction; Phase III Clinical Trials; Phenotype; Physicians; Population; Preparation; Prevention; Process; Provider; Randomized Clinical Trials; Randomized Controlled Trials; Rare Diseases; Research; Research Design; Site; Technology; Testing; Thinking; Third-Party Payer; Underrepresented Minority; Visit; base; burden of illness; care outcomes; clinical application; clinical care; clinical implementation; clinical sequencing; cost; cost effectiveness; data sharing; data standards; disadvantaged population; economic implication; evidence base; exome sequencing; expectation; experience; family burden; follow-up; genetic variant; genome sequencing; genome-wide; genomic data; health care service utilization; health disparity; improved; innovation; patient response; population health; programs; randomized controlled design; success; theories; therapy design; tool; treatment as usual; trial comparing; uptake; variant detection; whole genome

Project Summary/Abstract from original grant submission 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.

原始拨款提交的项目摘要/摘要 基因组测序技术的快速发展导致发现的 许多罕见疾病的遗传原因，改变了我们诊断和治疗遗传疾病的能力 条件。特别是，整个外显子组测序(WES)已被证明是一种非常成功的诊断方法 具有高度遗传异质性的患者的模式。作为临床的一部分 测序探索性研究(CSER)联盟，北卡罗来纳州临床基因组 下一代外显子组测序的评估“(NCGENES)解决了临床上的几个关键问题 外显子组测序的应用，包括WES在不同临床应用时的诊断率 情景、处理二次调查结果的最佳方法、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已广泛应用于临床。然而，在它能够广泛实施之前，付款人将需要 被说服常规地涵盖WES的使用；因此，必须解决关于其 临床应用。目前的续签，NCGENES 2，将通过以下方式提供必要的证据基础 联合一个高度跨学科的团队进行随机临床试验，以研究医疗保健结果和 患者、家属、临床医生和实验室之间的沟通。此外，NCGENES 2将 解决传统弱势群体中的这些问题，以确保基因组的好处 医学将惠及尽可能广泛的人群。NCGENES 2的每个目标都将 解决与临床Exome的实际实施高度相关的特定结果 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，4) 社会后果，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的标准工具的证据 并使其能够在经历健康差距的人群中实施。

项目成果

Incidental Findings with Genomic Testing: Implications for Genetic Counseling Practice.

• DOI: 10.1007/s40142-015-0075-9
• 发表时间: 2015
• 期刊: Current genetic medicine reports
• 影响因子: 2.1
• 作者: Roche MI;Berg JS
• 通讯作者: Berg JS

Combination of exome sequencing and immune testing confirms Aicardi-Goutières syndrome type 5 in a challenging pediatric neurology case.

外显子组测序和免疫检测相结合，在一个具有挑战性的儿科神经病学病例中证实了 5 型 Aicardi-Goutières 综合征。

• DOI: 10.1101/mcs.a002758
• 发表时间: 2018
• 期刊: Cold Spring Harbor molecular case studies
• 影响因子: 1.8
• 作者: Haskell,GloriaT;Mori,Mari;Powell,Cynthia;Amrhein,TimothyJ;Rice,GillianI;Bailey,Lauren;Strande,Natasha;Weck,KarenE;Evans,JamesP;Berg,JonathanS;Kishnani,Priya
• 通讯作者: Kishnani,Priya

Genomic screening of the general adult population: key concepts for assessing net benefit with systematic evidence reviews.

• DOI: 10.1038/gim.2014.129
• 发表时间: 2015-06
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics

Defining the Clinical Value of a Genomic Diagnosis in the Era of Next-Generation Sequencing.

定义下一代测序时代基因组诊断的临床价值。

• DOI: 10.1146/annurev-genom-083115-022348
• 发表时间: 2016-08-31
• 期刊: Annual review of genomics and human genetics
• 影响因子: 8.7
• 作者: Strande NT;Berg JS
• 通讯作者: Berg JS

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing.

• DOI: 10.1038/gim.2015.104
• 发表时间: 2016-05
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics
• 作者: Berg JS;Foreman AK;O'Daniel JM;Booker JK;Boshe L;Carey T;Crooks KR;Jensen BC;Juengst ET;Lee K;Nelson DK;Powell BC;Powell CM;Roche MI;Skrzynia C;Strande NT;Weck KE;Wilhelmsen KC;Evans JP
• 通讯作者: Evans JP