Abstract
In recent years, new sequencing technologies known as next generation sequencing (NGS) have provided scientists the ability to rapidly sequence all known coding as well as non-coding sequences in the human genome. As the two emerging approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to be integrated in the clinical arena, we sought to survey health care professionals who are likely to be involved in the implementation process now and/or in the future (e.g., genetic counselors, geneticists and nurse practitioners). Two hundred twenty-one genetic counselors— one third of whom currently offer WES/WGS—participated in an anonymous online survey. The aims of the survey were first, to identify barriers to the implementation of WES/WGS, as perceived by survey participants; second, to provide the first systematic report of current practices regarding the integration of WES/WGS in clinic and/or research across the US and Canada and to illuminate the roles and challenges of genetic counselors participating in this process; and third to evaluate the impact of WES/WGS on patient care. Our results showed that genetic counseling practices with respect to WES/WGS are consistent with the criteria set forth in the ACMG 2012 policy statement, which highlights indications for testing, reporting, and pre/post test considerations. Our respondents described challenges related to offering WES/WGS, which included billing issues, the duration and content of the consent process, result interpretation and disclosure of incidental findings and variants of unknown significance. In addition, respondents indicated that specialty area (i.e., prenatal and cancer), lack of clinical utility of WES/WGS and concerns about interpretation of test results were factors that prevented them from offering this technology to patients. Finally, study participants identified the aspects of their professional training which have been most beneficial in aiding with the integration of WES/WGS into the clinical setting (molecular/clinical genetics, counseling and bioethics) and suggested that counseling aids (to assist them when explaining aspects of these tests to patients) and webinars focused on WES/WGS (for genetic counselors and other health care professionals) would be useful educational tools. Future research should permit us to further enhance our knowledge of pitfalls and benefits associated with the introduction of these powerful technologies in patient care and to further explore the roles and opportunities for genetic counselors in this rapidly evolving field.
Similar content being viewed by others
References
American College of Medical Genetics and Genomics. (2012). Points to consider in the clinical application of genomic sequencing. Genetics in Medicine, 14, 759–761.
Ashley, E. A., Butte, A. J., Wheeler, M. T., Chen, R., Klein, T. E., Dewey, F. E., et al. (2010). Clinical assessment incorporating a personal genome. Lancet, 375(9725), 1525–1535.
Bras, J., Guerreiro, R., & Hardy, J. (2012). Use of next-generation sequencing and other whole-genome strategies to dissect neurological disease. Nature Reviews Neuroscience, 13(7), 453–464.
Brunham, L. R., & Hayden, M. R. (2012). Medicine. Whole-genome sequencing: the new standard of care? Science, 336(6085), 1112–1113.
Burniat, A., Pirson, I., Vilain, C., Kulik, W., Afink, G., Moreno-Reyes, R., et al. (2012). Iodotyrosine deiodinase defect identified via genome-wide approach. The Journal of Clinical Endocrinology and Metabolism, 97(7), 1276–1283.
Casals, F., & Bertranpetit, J. (2012). Genetics. Human genetic variation, shared and private. Science, 337(6090), 39–40.
Dixon-Salazar, T. J., Silhavy, J. L., Udpa, N., Schroth, J., Bielas, S., Schaffer, A. E., et al. (2012). Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine, 4(138), 138ra178.
Gonzaga-Jauregui, C., Lupski, J. R., & Gibbs, R. A. (2012). Human genome sequencing in health and disease. Annual Review of Medicine, 63, 35–61.
Green, R. C., Berg, J. S., Grody, W. W., Kalia, S. S., Korf, B. R., Martin, C. L., et al. (2013). ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in Medicine, 15(7), 565–574.
Gymrek, M., McGuire, A. L., Golan, D., Halperin, E., & Erlich, Y. (2013). Identifying personal genomes by surname inference. Science, 339(6117), 321–324.
Hastings, R., de Wert, G., Fowler, B., Krawczak, M., Vermeulen, E., Bakker, E., et al. (2012). The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe. European Journal of Human Genetics, 20, 911–916.
Krier, J. B., & Green, R. C. (2013). Management of incidental findings in clinical genomic sequencing. Current protocols in human genetics/editorial board, Jonathan L. Haines … [et al.], Chapter 9, Unit9 23.
Lam, H. Y., Clark, M. J., Chen, R., Natsoulis, G., O’Huallachain, M., Dewey, F. E., et al. (2012). Performance comparison of whole-genome sequencing platforms. Nature Biotechnology, 30(1), 78–82.
Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6822), 860–921.
Lerner-Ellis, J. P. (2012). The clinical implementation of whole genome sequencing: a conversation with seven scientific experts. Journal of Inherited Metabolic Disease, 35(4), 689–693.
McGuire, A. L., Joffe, S., Koenig, B. A., Biesecker, B. B., McCullough, L. B., Blumenthal-Barby, J. S., et al. (2013). Point-counterpoint. Ethics and genomic incidental findings. Science, 340(6136), 1047–1048.
Metzker, M. L. (2005). Emerging technologies in DNA sequencing. Genome Research, 15(12), 1767–1776.
Metzker, M. L. (2010). Sequencing technologies - the next generation. Nature Reviews Genetics, 11(1), 31–46.
Need, A. C., Shashi, V., Hitomi, Y., Schoch, K., Shianna, K. V., McDonald, M. T., et al. (2012). Clinical application of exome sequencing in undiagnosed genetic conditions. Journal of Medical Genetics, 49(6), 353–361.
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., et al. (2010). Exome sequencing identifies the cause of a mendelian disorder. Nature Genetics, 42(1), 30–35.
O’Daniel, J. M., & Lee, K. (2012). Whole-genome and whole-exome sequencing in hereditary cancer: impact on genetic testing and counseling. Cancer Journal, 18(4), 287–292.
Ormond, K. E., Wheeler, M. T., Hudgins, L., Klein, T. E., Butte, A. J., Altman, R. B., et al. (2010). Challenges in the clinical application of whole-genome sequencing. Lancet, 375(9727), 1749–1751.
Rabbani, B., Mahdieh, N., Hosomichi, K., Nakaoka, H., & Inoue, I. (2012). Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. Journal of Human Genetics, 57, 621–632.
Robinson, P. N., Krawitz, P., & Mundlos, S. (2011). Strategies for exome and genome sequence data analysis in disease-gene discovery projects. Clinical Genetics, 80(2), 127–132.
Ropers, H. H. (2012). On the future of genetic risk assessment. Journal of Community Genetics, 3(3), 229–236.
Stavrou, E. F., & Goriely, A. (2012). Santorini mutation detection meeting 2011: rapid advance in sequencing technology poses challenges for interpretation of genetic variations. Human Mutation, 33(10), 1497–1500.
Stenson, P. D., Ball, E. V., Howells, K., Phillips, A. D., Mort, M., & Cooper, D. N. (2009). The Human Gene Mutation Database: providing a comprehensive central mutation database for molecular diagnostics and personalized genomics. Human Genomics, 4(2), 69–72.
Tabor, H. K., Berkman, B. E., Hull, S. C., & Bamshad, M. J. (2011). Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. American Journal of Medical Genetics Part A, 155A(12), 2916–2924.
Tabor, H. K., Stock, J., Brazg, T., McMillin, M. J., Dent, K. M., Yu, J. H., et al. (2012). Informed consent for whole genome sequencing: a qualitative analysis of participant expectations and perceptions of risks, benefits, and harms. American Journal of Medical Genetics Part A, 158A(6), 1310–1319.
Townsend, A., Adam, S., Birch, P. H., Lohn, Z., Rousseau, F., & Friedman, J. M. (2012). “I want to know what’s in Pandora’s Box”: comparing stakeholder perspectives on incidental findings in clinical whole genomic sequencing. American Journal of Medical Genetics Part A, 158A(10), 2519–2525.
Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., et al. (2011). Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 13(3), 255–262.
Acknowledgments
We would like to thank survey participants for completing our on-line questionnaire. We are thankful to Ted Cross for providing advice on statistical methodology for the analysis of data and for reviewing statistical analysis presented in this paper. We would also like to thank Rimma Shakhbatyan for assistance with statistical analysis, Gretchen Schneider and Beth Sheidley of the Brandeis Genetic Counseling Program for their helpful discussions and valuable insight as well as Melissa Goldberg for administrative assistance. This project has received support from the Brandeis University Graduate School of Arts and Sciences Master’s Research Fund.
Disclosure of conflict of interest
Kalotina Machini, Jessica Douglas, Judith Tsipis and Kate Kramer declare that they have no conflict of interest. Alicia Braxton works for the Baylor College of Medicine Medical Genetics Laboratory, which derives revenue from clinical whole exome sequencing.
Informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants for being included in the study.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOCX 336 kb)
Rights and permissions
About this article
Cite this article
Machini, K., Douglas, J., Braxton, A. et al. Genetic Counselors’ Views and Experiences with the Clinical Integration of Genome Sequencing. J Genet Counsel 23, 496–505 (2014). https://doi.org/10.1007/s10897-014-9709-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10897-014-9709-4