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-HGR-N (O1))
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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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Amendola, Laura M; Jarvik, Gail P; Leo, Michael C et al. (2016) Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. Am J Hum Genet 98:1067-76
Richards, Julie E; Bane, Emmi; Fullerton, Stephanie M et al. (2016) Allocation of Resources to Communication of Research Result Summaries: Biobank Participant Perspectives. J Empir Res Hum Res Ethics :
Nishimura, Adam A; Shirts, Brian H; Salama, Joseph et al. (2016) Physician perspectives of CYP2C19 and clopidogrel drug-gene interaction active clinical decision support alerts. Int J Med Inform 86:117-25
Jarvik, Gail P; Browning, Brian L (2016) Consideration of Cosegregation in the Pathogenicity Classification of Genomic Variants. Am J Hum Genet 98:1077-81
Tan, Nina; Amendola, Laura M; O'Daniel, Julianne M et al. (2016) Is ""incidental finding"" the best term?: a study of patients' preferences. Genet Med :
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
O'Daniel, Julianne M; McLaughlin, Heather M; Amendola, Laura M et al. (2016) A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories. Genet Med :
Popejoy, Alice B; Fullerton, Stephanie M (2016) Genomics is failing on diversity. Nature 538:161-164
Korngiebel, Diane M; McMullen, Carmit K; Amendola, Laura M et al. (2016) Generating a taxonomy for genetic conditions relevant to reproductive planning. Am J Med Genet A 170:565-73
Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J et al. (2016) Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice. Cancer 122:393-401

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