Development and Validation of Clinical Whole-Exome and Whole-Genome Sequencing for Detection of Germline Variants in Inherited Disease.

Context.--With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing--based whole-exome and whole-genome sequencing. B...

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Publicado en:Archives of Pathology & Laboratory Medicine Vol. 141; no. 6; pp. 798 - 806
Autores principales: Hegde, Madhuri, Santani, Avni, Mao, Rong, Ferreira-Gonzalez, Andrea, Weck, Karen E., Voelkerding, Karl V.
Formato: tables/charts Journal Article
Publicado: College of American Pathologists Jun2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2017
      vid: 141
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      pub: College of American Pathologists
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        atl: Development and Validation of Clinical Whole-Exome and Whole-Genome Sequencing for Detection of Germline Variants in Inherited Disease.
      aug:
        au:
          Hegde, Madhuri
          Santani, Avni
          Mao, Rong
          Ferreira-Gonzalez, Andrea
          Weck, Karen E.
          Voelkerding, Karl V.
        affil: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia
      sug:
        subj:
          Genome
          Sequence Analysis
          Hereditary Diseases Physiopathology
          Human
          Validation Studies
          Molecular Biology
          Clinical Laboratories
          Phenotype
          Biological Assay
          Reports
          Bioinformatics
          Quality Assurance
          Pedigree
          Genetic Screening
      ab: Context.--With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing--based whole-exome and whole-genome sequencing. Because a large number of targets are covered by whole-exome and whole-genome sequencing, it is critical that a laboratory perform appropriate validation studies, develop a quality assurance and quality control program, and participate in proficiency testing. Objective.--To provide recommendations for wholeexome and whole-genome sequencing assay design, validation, and implementation for the detection of germline variants associated in inherited disorders. Data Sources.--An example of trio sequencing, filtration and annotation of variants, and phenotypic consideration to arrive at clinical diagnosis is discussed. Conclusions.--It is critical that clinical laboratories planning to implement whole-exome and whole-genome sequencing design and validate the assay to specifications and ensure adequate performance prior to implementation. Test design specifications, including variant filtering and annotation, phenotypic consideration, guidance on consenting options, and reporting of incidental findings, are provided. These are important steps a laboratory must take to validate and implement whole-exome and wholegenome sequencing in a clinical setting for germline variants in inherited disorders.
      pubtype: Academic Journal
      doctype:
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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