Technological developments in the field of genomics now afford the opportunity to define the complete sequence of an individual's genome in a rapid and affordable manner. Such """"""""whole genome sequencing"""""""" and its simpler corollary, """"""""whole exome sequencing"""""""" (WES), have already established themselves as powerful research tools. The natural next step in the evolution of this technology is its direct application in the clinical arena. However, while such technology holds considerable clinical promise, tremendous challenges exist in applying it and deriving practical benefit to patients. In this proposal we outline a highly interdisciplinary approach to identifying, confronting and overcoming the major challenges which must be met in order to implement deep sequencing technology in clinical medicine.
Aim 1 will explore the use of WES as a diagnostic tool in the care of a broad array of patients, evaluate its performance, identify critical clinical characteristics which can guide its application and measure the impact of such information on patients and providers.
Aim 2 will tackle one of the most pressing challenges in the clinical application of WES: the inevitable generation of """"""""collateral"""""""" or """"""""bystander"""""""" information. Educational materials will be developed to enable patients to make decisions about appropriate return of results and the impact of collateral information will be assessed at the level of the provider, laboratory and patient. The third major challenge in clinical implementation of genomic medicine, how do deal with vast amounts of information, will be addressed by Aim 3. A clinically oriented """"""""binning"""""""" structure will be created and refined for classifying, storing and transmitting data within practical categories so as to make sense of the large amounts of data generated. Finally, as we stand on the cusp of genomic medicine, we must ensure that all have access to its benefits. Thus, Aim 4 will pursue clinical WES in traditionally underrepresented populations to identify special opportunities and challenges in the clinical translation of this new tool to the broadest possible population. Our ultimate aim is to establish a set of best practices to guide future implementation of robust genomic technologies for the real and practical betterment of human health.

Public Health Relevance

Genomic medicine has tremendous potential to improve human health by facilitating improved diagnosis, offering deep insight into mechanisms of disease and by enabling individually targeted prevention and treatment. In this proposal we will confront the major challenges which stand between genomic medicine and its broad implementation to a diverse population.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHG1-HGR-N (O1))
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Hindorff, Lucia
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Christensen, Kurt D; Bernhardt, Barbara A; Jarvik, Gail P et al. (2018) Anticipated responses of early adopter genetic specialists and nongenetic specialists to unsolicited genomic secondary findings. Genet Med 20:1186-1195
Webber, Elizabeth M; Hunter, Jessica Ezzell; Biesecker, Leslie G et al. (2018) Evidence-based assessments of clinical actionability in the context of secondary findings: Updates from ClinGen's Actionability Working Group. Hum Mutat 39:1677-1685
Pawliczek, Piotr; Patel, Ronak Y; Ashmore, Lillian R et al. (2018) ClinGen Allele Registry links information about genetic variants. Hum Mutat 39:1690-1701
Haskell, Gloria T; Adams, Michael C; Fan, Zheng et al. (2018) Diagnostic utility of exome sequencing in the evaluation of neuromuscular disorders. Neurol Genet 4:e212
Amendola, Laura M; Robinson, Jill O; Hart, Ragan et al. (2018) Why Patients Decline Genomic Sequencing Studies: Experiences from the CSER Consortium. J Genet Couns 27:1220-1227
Roche, Myra I; Griesemer, Ida; Khan, Cynthia M et al. (2018) Factors influencing NCGENES research participants' requests for non-medically actionable secondary findings. Genet Med :
Porter, Kathryn M; Kauffman, Tia L; Koenig, Barbara A et al. (2018) Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience. Mol Genet Genomic Med 6:898-909
Rini, Christine; Khan, Cynthia M; Moore, Elizabeth et al. (2018) 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 20:760-769
Wolf, Susan M; Amendola, Laura M; Berg, Jonathan S et al. (2018) Navigating the research-clinical interface in genomic medicine: analysis from the CSER Consortium. Genet Med 20:545-553
Skinner, Debra; Roche, Myra I; Weck, Karen E et al. (2018) ""Possibly positive or certainly uncertain?"": participants' responses to uncertain diagnostic results from exome sequencing. Genet Med 20:313-319

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