Recommendations for the integration of genomics into clinical practice

Sarah Bowdin^{1

2}, Adel Gilbert¹, Emma Bedoukian^{3

4}, Christopher Carew¹, Margaret P Adam⁵, John Belmont⁶, Barbara Bernhardt⁷, Leslie Biesecker⁸, Hans T Bjornsson^{9

10}, Miriam Blitzer¹¹, Lisa C A D'Alessandro¹², Matthew A Deardorff^{3

4

13}, Laurie Demmer¹⁴, Alison Elliott¹⁵, Gerald L Feldman¹⁶, Ian A Glass⁵, Gail Herman¹⁷, Lucia Hindorff¹⁸, Fuki Hisama¹⁹, Louanne Hudgins²⁰, A Micheil Innes²¹, Laird Jackson²², Gail Jarvik¹⁸, Raymond Kim²², Bruce Korf²³, David H Ledbetter²⁴, Mindy Li²⁵, Eriskay Liston²², Christian Marshall²⁶, Livija Medne^{2

3}, M Stephen Meyn^{1

22}, Nasim Monfared²², Cynthia Morton²⁷, John J Mulvihill²⁸, Sharon E Plon²⁹, Heidi Rehm²⁷, Amy Roberts³⁰, Cheryl Shuman^{1

22}, Nancy B Spinner²⁵, D James Stavropoulos²⁶, Kathleen Valverde³¹, Darrel J Waggoner³², Alisha Wilkens^{3

4}, Ronald D Cohn^{1

22}, Ian D Krantz^{3

13}

Affiliations

¹ Centre for Genetic Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
² Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
³ Individualized Medical Genetics Center, Division of Human Genetics, Department of Pediatrics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁴ Individualized Medical Genetics Center, Division of Human Genetics, Department of Pathology, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵ Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington, USA.
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
⁷ Division of Translational Medicine and Human Genetics, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁹ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ Division of Human Genetics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹² Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
¹³ Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁴ Department of Pediatrics, Carolinas Medical Center, Charlotte, North Carolina, USA.
¹⁵ Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁶ Center for Molecular Medicine and Genetics and Department of Pediatrics and Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA.
¹⁷ Center for Molecular and Human Genetics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
¹⁸ Division of Genomic Medicine, National Human Genome Research Institute, National institutes of Health, Bethesda, Maryland, USA.
¹⁹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.
²⁰ Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
²¹ Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²² Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
²³ Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁴ Geisinger Health System, Danville, Pennsylvania, USA.
²⁵ Division of Genomic Diagnostics, Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁶ Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
²⁷ Department of Obstetrics, Gynecology and Reproductive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁸ Department of Pediatrics, University of Oklahoma, Oklahoma City, Oklahoma, USA.
²⁹ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
³⁰ Department of Cardiology and Division of Genetics, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³¹ College of Health Sciences, Arcadia University, Glenside, Pennsylvania, USA.
³² Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.

PMID: 27171546
PMCID: PMC5557020
DOI: 10.1038/gim.2016.17

Review

Recommendations for the integration of genomics into clinical practice

Sarah Bowdin et al. Genet Med. 2016 Nov.

. 2016 Nov;18(11):1075-1084.

doi: 10.1038/gim.2016.17. Epub 2016 May 12.

Authors

Affiliations

¹ Centre for Genetic Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
² Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
³ Individualized Medical Genetics Center, Division of Human Genetics, Department of Pediatrics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁴ Individualized Medical Genetics Center, Division of Human Genetics, Department of Pathology, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵ Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington, USA.
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
⁷ Division of Translational Medicine and Human Genetics, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁹ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹¹ Division of Human Genetics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹² Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
¹³ Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁴ Department of Pediatrics, Carolinas Medical Center, Charlotte, North Carolina, USA.
¹⁵ Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁶ Center for Molecular Medicine and Genetics and Department of Pediatrics and Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA.
¹⁷ Center for Molecular and Human Genetics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
¹⁸ Division of Genomic Medicine, National Human Genome Research Institute, National institutes of Health, Bethesda, Maryland, USA.
¹⁹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.
²⁰ Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
²¹ Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²² Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
²³ Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁴ Geisinger Health System, Danville, Pennsylvania, USA.
²⁵ Division of Genomic Diagnostics, Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁶ Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
²⁷ Department of Obstetrics, Gynecology and Reproductive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁸ Department of Pediatrics, University of Oklahoma, Oklahoma City, Oklahoma, USA.
²⁹ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
³⁰ Department of Cardiology and Division of Genetics, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³¹ College of Health Sciences, Arcadia University, Glenside, Pennsylvania, USA.
³² Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.

PMID: 27171546
PMCID: PMC5557020
DOI: 10.1038/gim.2016.17

Abstract

The introduction of diagnostic clinical genome and exome sequencing (CGES) is changing the scope of practice for clinical geneticists. Many large institutions are making a significant investment in infrastructure and technology, allowing clinicians to access CGES, especially as health-care coverage begins to extend to clinically indicated genomic sequencing-based tests. Translating and realizing the comprehensive clinical benefits of genomic medicine remain a key challenge for the current and future care of patients. With the increasing application of CGES, it is necessary for geneticists and other health-care providers to understand its benefits and limitations in order to interpret the clinical relevance of genomic variants identified in the context of health and disease. New, collaborative working relationships with specialists across diverse disciplines (e.g., clinicians, laboratorians, bioinformaticians) will undoubtedly be key attributes of the future practice of clinical genetics and may serve as an example for other specialties in medicine. These new skills and relationships will also inform the development of the future model of clinical genetics training curricula. To address the evolving role of the clinical geneticist in the rapidly changing climate of genomic medicine, two Clinical Genetics Think Tank meetings were held that brought together physicians, laboratorians, scientists, genetic counselors, trainees, and patients with experience in clinical genetics, genetic diagnostics, and genetics education. This article provides recommendations that will guide the integration of genomics into clinical practice.Genet Med 18 11, 1075-1084.

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Conflict of interest statement

Conflict of Interest

The authors of this manuscript declare no conflict of interest.

Figures

**Figure 1. Algorithm to help identify patients most likely to benefit from clinical genome and exome sequencing (CGES)**
Genetic testing should be a phenotype-driven process, taking into account the most current knowledge of the genetic basis of the condition(s) undergoing investigation. The decision to order CGES versus a targeted panel will be informed by the genetic heterogeneity of the condition, depth of coverage for genes of interest, and the cost of each test. *Consider CGES as a first-line test when there is parental consanguinity. FISH, fluorescent in situ hybridization.

**Figure 2**
Suggested post-clinical genome and exome sequencing patient-care algorithm.

See this image and copyright information in PMC

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Recommendations for the integration of genomics into clinical practice

Affiliations

Recommendations for the integration of genomics into clinical practice

Authors

Affiliations

Abstract

Conflict of interest statement

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Grants and funding

LinkOut - more resources

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