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.

Public Health Relevance

Genomic sequencing has the potential to allow patients with heterogeneous genetic disorders to receive a prompt and specific molecular diagnosis, allowing physicians, patients and families to benefit from early management, treatment and prevention. In this proposal we will generate the evidence necessary for a variety of stakeholders (patients, physicians, and payers) to determine when the use of this technology will result in an overall benefit.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HG006487-06
Application #
9537665
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Madden, Ebony B
Project Start
2011-12-05
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Vora, Neeta L; Powell, Bradford; Brandt, Alicia et al. (2017) Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges. Genet Med 19:1207-1216
Wolf, Susan M; Amendola, Laura M; Berg, Jonathan S et al. (2017) Navigating the research-clinical interface in genomic medicine: analysis from the CSER Consortium. Genet Med :
O'Daniel, Julianne M; McLaughlin, Heather M; Amendola, Laura M et al. (2017) A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories. Genet Med 19:575-582
Haskell, Gloria T; Jensen, Brian C; Samsa, Leigh Ann et al. (2017) Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease. Circ Cardiovasc Genet 10:
Berg, Jonathan S (2017) Exploring the importance of case-level clinical information for variant interpretation. Genet Med 19:3-5
Rini, Christine; Khan, Cynthia M; Moore, Elizabeth et al. (2017) The who, what, and why of research participants' intentions to request a broad range of secondary findings in a diagnostic genomic sequencing study. Genet Med :
Sanghvi, Rashesh V; Buhay, Christian J; Powell, Bradford C et al. (2017) Characterizing reduced coverage regions through comparison of exome and genome sequencing data across 10 centers. Genet Med :
Skinner, Debra; Raspberry, Kelly A; King, Martha (2016) The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing. Sociol Health Illn 38:1303-1317
Leos, Cristina; Khan, Cynthia M; Rini, Christine (2016) Understanding self-management behaviors in symptomatic adults with uncertain etiology using an illness perceptions framework. J Behav Med 39:310-9
Rasmussen, Luke V; Overby, Casey L; Connolly, John et al. (2016) Practical considerations for implementing genomic information resources. Experiences from eMERGE and CSER. Appl Clin Inform 7:870-82

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