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Evaluating the Clinical Validity of Gene-Disease Associations: An Evidence-Based Framework Developed by the Clinical Genome Resource.
Strande, Natasha T; Riggs, Erin Rooney; Buchanan, Adam H; Ceyhan-Birsoy, Ozge; DiStefano, Marina; Dwight, Selina S; Goldstein, Jenny; Ghosh, Rajarshi; Seifert, Bryce A; Sneddon, Tam P; Wright, Matt W; Milko, Laura V; Cherry, J Michael; Giovanni, Monica A; Murray, Michael F; O'Daniel, Julianne M; Ramos, Erin M; Santani, Avni B; Scott, Alan F; Plon, Sharon E; Rehm, Heidi L; Martin, Christa L; Berg, Jonathan S.
Afiliación
  • Strande NT; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Riggs ER; Autism & Developmental Medicine Institute, Geisinger Health System, Danville, PA 17837, USA.
  • Buchanan AH; Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA.
  • Ceyhan-Birsoy O; Laboratory for Molecular Medicine, Partners Personalized Medicine, Boston, MA 02139, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA.
  • DiStefano M; Laboratory for Molecular Medicine, Partners Personalized Medicine, Boston, MA 02139, USA.
  • Dwight SS; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Goldstein J; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Ghosh R; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Seifert BA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Sneddon TP; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Wright MW; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Milko LV; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Cherry JM; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Giovanni MA; Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA.
  • Murray MF; Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA.
  • O'Daniel JM; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Ramos EM; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Santani AB; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Scott AF; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Plon SE; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Rehm HL; Laboratory for Molecular Medicine, Partners Personalized Medicine, Boston, MA 02139, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA.
  • Martin CL; Autism & Developmental Medicine Institute, Geisinger Health System, Danville, PA 17837, USA; Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA. Electronic address: clmartin1@geisinger.edu.
  • Berg JS; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA. Electronic address: jonathan_berg@med.unc.edu.
Am J Hum Genet ; 100(6): 895-906, 2017 Jun 01.
Article en En | MEDLINE | ID: mdl-28552198
With advances in genomic sequencing technology, the number of reported gene-disease relationships has rapidly expanded. However, the evidence supporting these claims varies widely, confounding accurate evaluation of genomic variation in a clinical setting. Despite the critical need to differentiate clinically valid relationships from less well-substantiated relationships, standard guidelines for such evaluation do not currently exist. The NIH-funded Clinical Genome Resource (ClinGen) has developed a framework to define and evaluate the clinical validity of gene-disease pairs across a variety of Mendelian disorders. In this manuscript we describe a proposed framework to evaluate relevant genetic and experimental evidence supporting or contradicting a gene-disease relationship and the subsequent validation of this framework using a set of representative gene-disease pairs. The framework provides a semiquantitative measurement for the strength of evidence of a gene-disease relationship that correlates to a qualitative classification: "Definitive," "Strong," "Moderate," "Limited," "No Reported Evidence," or "Conflicting Evidence." Within the ClinGen structure, classifications derived with this framework are reviewed and confirmed or adjusted based on clinical expertise of appropriate disease experts. Detailed guidance for utilizing this framework and access to the curation interface is available on our website. This evidence-based, systematic method to assess the strength of gene-disease relationships will facilitate more knowledgeable utilization of genomic variants in clinical and research settings.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Genómica / Estudios de Asociación Genética Tipo de estudio: Guideline / Prognostic_studies / Qualitative_research / Risk_factors_studies Límite: Humans Idioma: En Revista: Am J Hum Genet Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Genómica / Estudios de Asociación Genética Tipo de estudio: Guideline / Prognostic_studies / Qualitative_research / Risk_factors_studies Límite: Humans Idioma: En Revista: Am J Hum Genet Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos