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Next-generation sequencing in the clinic: are we ready?


We are entering an era in which the cost of clinical whole-genome and targeted sequencing tests is no longer prohibitive to their application. However, currently the infrastructure is not in place to support both the patient and the physicians that encounter the resultant data. Here, we ask five experts to give their opinions on whether clinical data should be treated differently from other medical data, given the potential use of these tests, and on the areas that must be developed to improve patient outcome.

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  1. Burson, C. M. & Markey, K. R. Genetic counseling issues in predictive genetic testing for familial adult-onset neurologic diseases. Seminars Pediatr. Neurol. 8, 177–186 (2001).

    Article  CAS  Google Scholar 

  2. Evans, J. P. & Rothschild, B. B. Return of results: not that complicated? Genet. Med. 14, 358–360 (2012).

    Article  Google Scholar 

  3. Biesecker, L. G. Opportunities and challenges for the integration of massively parallel genomic sequencing into clinical practice: lessons from the ClinSeq project. Genet. Med. 14, 393–398 (2012).

    Article  Google Scholar 

  4. Kohane, I. S., Hsing, M. & Kong, S. W. Taxonomizing, sizing, and overcoming the incidentalome. Genet. Med. 14, 399–404 (2012).

    Article  CAS  Google Scholar 

  5. Institute of Medicine of the National Academies. Integrating large-scale genomic information into clinical practice: workshop summary (National Academies Press, 2012).

  6. Mennuti, M. T. Genetic screening in reproductive health care. Clin. Obstet. Gynecol. 51, 3–23 (2008).

    Article  Google Scholar 

  7. Goldman, J. S. et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet. Med. 13, 597–605 (2011).

    Article  Google Scholar 

  8. Burke, W. Genetic testing. New Engl. J. Med. 347, 1867–1875 (2002).

    Article  CAS  Google Scholar 

  9. Patay, B. A. & Topol, E. J. The unmet need of education in genomic medicine. Am. J. Med. 125, 5–6 (2012).

    Article  Google Scholar 

  10. Sifri, R. et al. Use of cancer susceptibility testing among primary care physicians. Clin. Genet. 64, 355–360 (2003).

    Article  CAS  Google Scholar 

  11. Wideroff, L. et al. Physician use of genetic testing for cancer susceptibility: results of a national survey. Cancer Epidemiol. Biomarkers Prev. 12, 295–303 (2003).

    PubMed  Google Scholar 

  12. Scheuner, M. et al. Are electronic health records ready for genomic medicine? Genet. Med. 11, 510–517 (2009).

    Article  Google Scholar 

  13. Tversky, A. & Kahneman, D. Judgment under uncertainty: heuristics and biases. Science 185, 1124–1131 (1974).

    Article  CAS  Google Scholar 

  14. Szolovits, P. & Pauker, S. G. Categorical and probabilistic reasoning in medical diagnosis. Artif. Intelligence Med. 11, 115–144 (1978).

    Article  Google Scholar 

  15. Lin, Z., Altman, R. B. & Owen, A. B. Confidentiality in genome research. Science 313, 441–442 (2006).

    Article  CAS  Google Scholar 

  16. Potter, N. T., Spector, E. B. & Prior, T. W. Technical standards and guidelines for Huntington disease testing. Genet. Med. 6, 61–65 (2004).

    Article  Google Scholar 

  17. Johnston, J. J. et al. Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Am. J. Hum. Genet. 91, 97–108 (2012).

    Article  CAS  Google Scholar 

  18. Riley, B. D. et al. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J. Genet. Couns. 21, 151–161 (2012).

    Article  Google Scholar 

  19. Plon, S. E. et al. Genetic testing and cancer risk management recommendations by physicians for at-risk relatives. Genet. Med. 13, 148–154 (2011).

    Article  Google Scholar 

  20. Goldgar, D. E., Easton, D. F., Cannon-Albright, L. A. & Skolnick, M. H. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J. Natl Cancer Inst. 86, 1600–1608 (1994).

    Article  CAS  Google Scholar 

  21. Biesecker, L. G. et al. The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicine. Genome Res. 19, 1665–1674 (2009).

    Article  CAS  Google Scholar 

  22. Lesser, C. S., Lucey, C. R., Egener, B., Braddock, C. H., Linas, S. L. & Levinson, W. A behavioral and systems view of professionalism. JAMA 304, 2732–2737 (2010).

    Article  CAS  Google Scholar 

  23. Kohane, I. S., Masys, D. R. & Altman, R. B. The incidentalome: a threat to genomic medicine. JAMA 296, 212–215 (2006).

    Article  CAS  Google Scholar 

  24. Roberts, N. J. et al. The predictive capacity of personal genome sequencing. Sci. Transl. Med. 4, 133ra58 (2012).

    Article  Google Scholar 

  25. Gahl, W. A. et al. The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases. Genet. Med. 14, 51–59 (2012).

    Article  CAS  Google Scholar 

  26. Maxmen, A. Exome sequencing deciphers rare diseases. Cell 144, 635–637 (2011).

    Article  CAS  Google Scholar 

  27. Mayer, A. N. et al. A timely arrival for genomic medicine. Genet. Med. 13, 195–196 (2011).

    Article  Google Scholar 

  28. Berg, J. S. et al. An informatics approach to analyzing the incidentalome. Genet. Med. 27 Jul 2012 (doi:10.1038/gim.2012.112).

  29. Hicks, J. K. et al. A clinician-driven automated system for integration of pharmacogenetic interpretations into an electronic medical record. Clin. Pharmacol. Ther. 19 Sep 2012 (doi:10.1038/clpt.2012.140).

  30. Overby, C. L., Tarczy-Hornoch, P., Hoath, J. I., Kalet, I. J. & Veenstra, D. L. Feasibility of incorporating genomic knowledge into electronic medical records for pharmacogenomic clinical decision support. BMC Bioinformatics 11 (Suppl. 9), S10 (2010).

    Article  Google Scholar 

  31. Guttmacher, A. E., Jenkins, J. & Uhlmann, W. R. Genomic medicine: who will practice it? A call to open arms. Am. J. Med. Genet. 106, 216–222 (2001).

    Article  CAS  Google Scholar 

  32. Millot, G. A. et al. A guide for functional analysis of BRCA1 variants of uncertain significance. Hum. Mutat. 16 Jul 2012 (doi:10.1002/humu.22150).

  33. Wright, C. et al. Next steps in the sequence: the implications of whole genome sequencing for health in the UK Ch. 12 153–160 (PHG Foundation, 2011).

    Google Scholar 

  34. Wright, C. et al. Next steps in the sequence: the implications of whole genome sequencing for health in the UK Ch. 4 33–44 (PHG Foundation, 2011).

    Google Scholar 

  35. Farley, T. A. Reforming health care or reforming health? Am. J. Public Health. 99, 588–590 (2009).

    Article  Google Scholar 

  36. Committee on a Framework for Development a New Taxonomy of Disease; National Research Council. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease (National Academies Press, 2011).

  37. Qi, Q. et al. Sugar-sweetened beverages and genetic risk of obesity. N. Engl. J. Med. 21 Sep 2012 (doi:10.1056/NEJMoa1203039).

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L.G.B. and the ClinSeq program are supported by the Intramural Research Program of the US National Human Genome Research Institute. S.E.P. acknowledges grant 1 U01 HG006485. R.Z. would like to thank M. Kroese and A. Hall, both of the PHG Foundation, for helpful discussion. The opinions expressed are the authors' own and do not necessarily reflect the views of the institutions with which they are affiliated.

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Correspondence to Leslie G. Biesecker, Wylie Burke, Isaac Kohane, Sharon E. Plon or Ron Zimmern.

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Leslie G. Biesecker is an uncompensated consultant to and collaborator with the Illumina Corporation. Wylie Burke, Isaac Kohane, Sharon E. Plon and Ron Zimmern declare no competing financial insterests.

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Biesecker, L., Burke, W., Kohane, I. et al. Next-generation sequencing in the clinic: are we ready?. Nat Rev Genet 13, 818–824 (2012).

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