title: Targeted next-generation sequencing panels for monogenetic disorders in clinical diagnostics: the opportunities and challenges.
abstract: Next-generation sequencing (NGS) will soon be used for clinically heterogeneous, inherited disorders and the increasing number of disease-causing genes reported. Diagnostic laboratories therefore need to decide which NGS methods they are going to invest in and how to implement them. We discuss here the challenges and opportunities of using targeted resequencing (TRS) panels for diagnosing monogenetic disorders. Of the different NGS approaches available, TRS panels offer the opportunity to sequence and analyze a limited set of predetermined target genes. At present, TRS panels offer better base-pair coverage, running times, costs and dataset handling than other NGS applications such as whole genome sequencing and whole exome sequencing. However, working with TRS panels also poses new challenges in variant interpretation, data handling and bioinformatic analyses. To optimize the analyses, TRS panel testing should be performed by bioinformaticians, clinicians and laboratory staff in close collaboration.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, CB 50, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: de Koning
authors.forename: Jan D H
authors.initials: JD
authors.lastname: Jongbloed
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sinke
mesh_terms: D030541:Databases, Genetic; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics; D005820:Genetic Testing / Q000191:economics* / Q000941:ethics; D059014:High-Throughput Nucleotide Sequencing / Q000191:economics* / Q000941:ethics; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000191:economics / Q000941:ethics; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000191:economics / Q000941:ethics
keywords: DNA diagnostics; coverage; incidental finding; next-generation sequencing; sequence depth; targeted resequencing panel; variant interpretation