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.
Bibliographical noteFunding 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.
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.
© 2016 American Society of Human Genetics.