title: The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists.
abstract: OBJECTIVE
  The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals.
  Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada.
  
  
  CONCLUSIONS
  Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally.
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Kym
authors.initials: K
authors.lastname: Boycott
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Taila
authors.initials: T
authors.lastname: Hartley
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shelin
authors.initials: S
authors.lastname: Adam
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Bernier
authors.affiliation: The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Chong
authors.affiliation: Disciplines of Genetics and Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Fernandez
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Friedman
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Geraghty
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Stacey
authors.initials: S
authors.lastname: Hume
authors.affiliation: McGill University and Centre of Genomics and Policy, Montréal, Québec, Canada.
authors.forename: Bartha M
authors.initials: BM
authors.lastname: Knoppers
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine and Departments of Pediatrics and Neurosciences, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Laberge
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Québec, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.affiliation: The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada The Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: M Stephen
authors.initials: MS
authors.lastname: Meyn
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine and Departments of Pediatrics and Neurosciences, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Nelson
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Richer
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
authors.forename: Bekim
authors.initials: B
authors.lastname: Sadikovic
authors.affiliation: Maritime Medical Genetics Program, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Skidmore
authors.affiliation: Division of Molecular Genetics, Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Tracy
authors.initials: T
authors.lastname: Stockley
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sherry
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Clara
authors.initials: C
authors.lastname: van Karnebeek
authors.affiliation: McGill University and Centre of Genomics and Policy, Montréal, Québec, Canada.
authors.forename: Ma'n H
authors.initials: MH
authors.lastname: Zawati
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Lauzon
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Armour
mesh_terms: D002170:Canada; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics; D005826:Genetics, Medical / Q000379:methods* / Q000639:trends; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods* / Q000639:trends; D057170:Translational Research, Biomedical / Q000379:methods* / Q000639:trends
keywords: Canadian Healthcare System; Genome-Wide Sequencing; Position Statement; Return of Results