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

基本信息

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
项目类别：
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

项目摘要

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.

原始赠款提交的项目摘要/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的能力状况。特别是，整个外显子组测序（WES）已被证明是非常成功的诊断条件患者具有高度遗传异质性的患者的模态。作为临床的一部分 UNC项目的测序探索性研究（CSER）财团，“北卡罗来纳州临床基因组下一代外显子组测序的评估”（NCGENES）解决了临床中的几个关键问题外显子组测序的应用，包括在潜水员临床中应用WES时的诊断产量方案，处理次要发现的最佳方法，知情同意程序和患者和家庭对基因组信息的反应。部分原因是CSER计划的成功， WES已在临床上广泛使用。但是，在可以广泛实施之前，付款人需要被说服定期涵盖WES的使用；因此，必须解决有关它的关键问题临床实用程序。当前的续约NCGENES 2将通过带来这个必要的证据基础一个高度跨学科的团队共同进行随机临床试验，以研究医疗结果和患者，家庭成员，临床医生和实验室之间的沟通。而且，NCGENES 2将在传统上处于弱势群体中解决这些问题，以确保基因组的益处医学将接受最广泛的人群。 NCGENES 2的每个目标都将解决与临床外显子的现实世界实施高度相关的特定结果测序：1）技术和分析结果，2）以患者为中心的结果，3）临床结果和4）社会成果，包括经济影响。最终，NCGENES 2将生成必要的支持使用WES作为遗传疾病患者管理的标准工具的证据并在体验健康分配的人群中实施其实施。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

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
影响因子：
0
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

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