Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Robert C. Green, Katrina A B Goddard, Gail P. Jarvik, Laura M. Amendola, Paul S. Appelbaum, Jonathan S. Berg, Barbara A. Bernhardt, Leslie G. Biesecker, Sawona Biswas, Carrie L. Blout, Kevin M. Bowling, Kyle B. Brothers, Wylie Burke, Charlisse F. Caga-Anan, Arul M. Chinnaiyan, Wendy K. Chung, Ellen W. Clayton, Gregory M. Cooper, Kelly East, James P. EvansStephanie M. Fullerton, Levi A. Garraway, Jeremy R. Garrett, Stacy W. Gray, Gail E. Henderson, Lucia A. Hindorff, Ingrid A. Holm, Michelle Huckaby Lewis, Carolyn M. Hutter, Pasi A. Janne, Steven Joffe, David Kaufman, Bartha M. Knoppers, Barbara A. Koenig, Ian D. Krantz, Teri A. Manolio, Laurence McCullough, Jean McEwen, Amy McGuire, Donna Muzny, Richard M. Myers, Deborah A. Nickerson, Jeffrey Ou, Donald W. Parsons, Gloria M. Petersen, Sharon E. Plon, Heidi L. Rehm, J. Scott Roberts, Dan Robinson, Joseph S. Salama, Sarah Scollon, Richard R. Sharp, Brian Shirts, Nancy B. Spinner, Holly K. Tabor, Peter Tarczy-Hornoch, David L. Veenstra, Nikhil Wagle, Karen Weck, Benjamin S. Wilfond, Kirk Wilhelmsen, Susan M. Wolf, Julia Wynn, Joon Ho Yu, Michelle Amaral, Samuel J. Aronson, Shubhangi Arora, Danielle R. Azzariti, Greg S. Barsh, E. M. Bebin, Barbara B. Biesecker, Brian L. Brown, Amber A. Burt, Peter H. Byers, Muge G. Calikoglu, Sara J. Carlson, Nizar Chahin, Kurt D. Christensen, Allison L. Cirino, Laura K. Conlin, Greg M. Cooper, David R. Crosslin, James V. Davis, Kelly Davis, Matthew A. Deardorff, Batsal Devkota, Raymond De Vries, Pamela Diamond, Michael O. Dorschner, Noreen P. Dugan, Dmitry Dukhovny, Matthew C. Dulik, Kelly M. East, Edgar A. Rivera-Munoz, Barbara Evans, Jessica Everett, Nicole Exe, Zheng Fan, Lindsay Z. Feuerman, Kelly Filipski, Candice R. Finnila, Kristen Fishler, Bob Ghrundmeier, Karen Giles, Marian J. Gilmore, Zahra S. Girnary, Steven Gonsalves, Adam S. Gordon, Michele C. Gornick, William M. Grady, David E. Gray, Robert S. Greenwood, Amanda M. Gutierrez, Paul Han, Ragan Hart, Patrick Heagerty, Naomi Hensman, Susan M. Hiatt, Patricia Himes, Fuki M. Hisama, Carolyn Y. Ho, Lily B. Hoffman-Andrews, Celine Hong, Martha J. Horike-Pyne, Sara Hull, Seema Jamal, Brian C. Jensen, Jennifer Johnston, Dean Karavite, Tia L. Kauffman, Dave Kaufman, Whitley Kelley, Jerry H. Kim, Christine Kirby, William Klein, Sek Won Kong, Joel B. Krier, Neil E. Lamb, Michele P. Lambert, Lan Q. Le, Matthew S. Lebo, Alexander Lee, Kaitlyn B. Lee, Niall Lennon, Michael C. Leo, Kathleen A. Leppig, Katie Lewis, Neal I. Lindeman, Nicole Lockhart, Bob Lonigro, Edward J. Lose, Philip J. Lupo, Laura Lyman Rodriguez, Frances Lynch, Kalotina Machini, Calum Macrae, Daniel S. Marchuk, Josue N. Martinez, Aaron Masino, Heather M. McLaughlin, Carmit McMullen, Piotr A. Mieczkowski, Jeff Miller, Victoria A. Miller, Rajen Mody, Sean D. Mooney, Elizabeth G. Moore, Elissa Morris, Michael Murray, David Ng, Nelly M. Oliver, Will Parsons, Donald L. Patrick, Jeffrey Pennington, Denise L. Perry, Katie Porter, Bradford C. Powell, Sumit Punj, Carmen Radecki Breitkopf, Robin A. Raesz-Martinez, Wendy H. Raskind, Dean A. Reigar, Jacob A. Reiss, Carla A. Rich, Carolyn Sue Richards, Christine Rini, Scott Roberts, Peggy D. Robertson, Jill O. Robinson, Marguerite E. Robinson, Myra I. Roche, Edward J. Romasko, Elisabeth A. Rosenthal, Maria I. Scarano, Jennifer Schneider, Christine E. Seidman, Bryce A. Seifert, Brian H. Shirts, Lynette M. Sholl, Javed Siddiqui, Elian Silverman, Shirley Simmons, Janae V. Simons, Debra Skinner, Elena Stoffel, Natasha T. Strande, Shamil Sunyaev, Virginia P. Sybert, Jennifer Taber, Deanne M. Taylor, Christine R. Tilley, Ashley Tomlinson, Susan Trinidad, Ellen Tsai, Eliezer M. Van Allen, Jason L. Vassy, Pankaj Vats, Victoria L. Vetter, Raymond D. Vries, Sarah A. Walser, Rebecca C. Walsh, Allison Werner-Lin, Jana Whittle, Kirk C. Wilhelmsen, Yaping Yang, Carol Young, Brian J. Zikmund-Fisher

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.

Original languageEnglish (US)
Pages (from-to)1051-1066
Number of pages16
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - Jun 2 2016

Bibliographical note

Funding Information:
R.C.G. has received compensation for advisory services or speaking from Invitae, Prudential, Illumina, AIA, Helix, and Roche. L.G.B. receives royalties from Genentech and Amgen Corporations and is an uncompensated advisor to Illumina. W.K.C. is a consultant for BioRefrence Laboratories. L.A.G. is a consultant for Foundation Medicine, Novartis, and Boehringer Ingelheim, is an equity holder in Foundation Medicine, and is a member of the scientific advisory board at Warp Drive. He receives sponsored research support from Novartis. D.M. and S.E.P. are employees of Baylor College of Medicine (BCM). BCM and Miraca Holdings Inc. have formed a joint venture, Baylor Miraca Genetics Laboratories, with shared ownership and governance of the clinical genetics diagnostic laboratories. S.E.P. is on the scientific advisory board of Baylor Miraca Genetics Laboratories. N.W. is a shareholder of Foundation Medicine.

Funding Information:
The authors thank Julia Fekecs of the National Human Genome Research Institute (NHGRI) for her technical assistance with Figure 1 . The authors would like to thank all of the Clinical Sequencing Exploratory Research (CSER) participants for their involvement in this research. The authors also thank the members of their CSER advisory panel: Katrina Armstrong, MD; Rex L. Chisholm, PhD; Mildred K. Cho, PhD; Chanita H. Halbert, PhD; Elaine Lyon, PhD; Kenneth Offit, MD; Dan Roden, MD; Pamela Sankar, PhD; and Alan Williamson, PhD. The research described in this report was funded by grants U01HG0006546, U01HG006485, U01HG006500, U01HG006492, UM1HG007301, UM1HG007292, UM1HG006508, U01HG006487, U01HG006507, U01HG007307, U01HG006379, U41HG006834, U54HG003273, R21HG006596, P20HG007243, R01HG006600, P50HG007257, R01HG006600, R01HG004500, R01CA154517, R01HG006618, R21HG006594, R01HG006615, R21HG006612, 5R21HG006613, R01HG007063, HG008685, UL1TR000423, UA01AG047109, and K99HG007076. ClinSeq is supported by the NHGRI Intramural Research Program. C.F.C.-A., L.A.H., C.M.H., D.K., T.A.M., and J.M. are members of the NIH CSER staff team, responsible for management of the CSER program.

Publisher Copyright:
© 2016 American Society of Human Genetics.


Dive into the research topics of 'Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine'. Together they form a unique fingerprint.

Cite this