Since the completion of the Human Genome Project in 2001, there have been great expectations for translating human genomic information directly into clinically practice. During the last several years, numerous large studies have cataloged human DNA variation. In parallel, advances in DNA sequencing technologies have increased the throughput and decreased costs. We are now positioned to broadly deploy our knowledge of human genetic variation, coupled with high-throughput DNA sequencing methods, for individualized, large-scale medical resequencing to comprehensively reveal the genetic mechanisms underlying disease and influence clinical treatment. This base pairs to bedside translation requires multidisciplinary study. The University of Washington is a leader in clinical genetics (Bennett, Burke, Byers, Hisama, and Jarvik, Motulsky, Raskind, and Sybert), bioethics (Burke, Jarvik, Fullerton, and Trinidad), second-generation sequencing, variant calling and annotation (Rieder and Nickerson), disease gene discovery (Browning, Heagerty, Jarvik, Nickerson, and Rieder), medical informatics (Tarczy-Hornoch), and health services research (Heagerty, Patrick, Regier, and Veenstra). In this highly integrated proposal, we combine these strengths to investigate aspects of using exomic data clinically. We propose a randomized controlled trial of usual care vs. the addition of exome analysis in University of Washington Medical Genetics Clinic patients who have clinical indications for colorectal cancer/polyposis (CRCP) genetic testing. We will evaluate the effectiveness of this technology for the identification of clinically relevant CRCP gene mutations, cost, and patient derived measures. After deliberations by experts to identify variants that are incidental findings that should be returned, we will also return CLIA certified results to the participants. We will obtain structured feedback from subjects in both the usual care and exome arms of the RCT to evaluate their experiences. We will further consider the input of referring physicians and patients using focus groups. We will investigate the legal basis of the need to return CLIA certified research results. An important component of our work is determination of not only which results to return, but how best to incorporate these genomic data into the medical record. Finally, we will perform CRCP gene discovery studies for families without identifiable CRCP mutations; such novel gene discovery can impact prevention and treatment.

Public Health Relevance

The use of exome data in clinical medicine is a transformative technology. It offers the possibility of faster, less expensive and more complete resolution of genetic diagnoses as well as personalized prevention and treatment. Here we apply a multidisciplinary team to evaluate clinical genomics applied to colorectal cancer.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHG1)
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Hindorff, Lucia
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Patel, Ronak Y; Shah, Neethu; Jackson, Andrew R et al. (2017) ClinGen Pathogenicity Calculator: a configurable system for assessing pathogenicity of genetic variants. Genome Med 9:3
Deverka, Patricia A; Majumder, Mary A; Villanueva, Angela G et al. (2017) Creating a data resource: what will it take to build a medical information commons? Genome Med 9:84
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
Laurino, Mercy Y; Truitt, Anjali R; Tenney, Lederle et al. (2017) Clinical verification of genetic results returned to research participants: findings from a Colon Cancer Family Registry. Mol Genet Genomic Med 5:700-708
Evans, Barbara J; Jarvik, Gail P (2017) Impact of HIPAA's minimum necessary standard on genomic data sharing. Genet Med :
Evans, Barbara J (2017) Power to the People: Data Citizens in the Age of Precision Medicine. Vanderbilt J Entertain Technol Law 19:243-265
Jarvik, Gail P; Evans, James P (2017) Mastering genomic terminology. Genet Med 19:491-492
Goodman, Jessie L; Amendola, Laura M; Horike-Pyne, Martha et al. (2017) Discordance in selected designee for return of genomic findings in the event of participant death and estate executor. Mol Genet Genomic Med 5:172-176
Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P et al. (2017) Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing. Contemp Clin Trials 53:100-105

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