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Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples.
Wijngaard, Robin; Demidov, German; O'Gorman, Luke; Corominas-Galbany, Jordi; Yaldiz, Burcu; Steyaert, Wouter; de Boer, Elke; Vissers, Lisenka E L M; Kamsteeg, Erik-Jan; Pfundt, Rolph; Swinkels, Hilde; den Ouden, Amber; Te Paske, Iris B A W; de Voer, Richarda M; Faivre, Laurence; Denommé-Pichon, Anne-Sophie; Duffourd, Yannis; Vitobello, Antonio; Chevarin, Martin; Straub, Volker; Töpf, Ana; van der Kooi, Anneke J; Magrinelli, Francesca; Rocca, Clarissa; Hanna, Michael G; Vandrovcova, Jana; Ossowski, Stephan; Laurie, Steven; Gilissen, Christian.
Afiliación
  • Wijngaard R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Demidov G; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
  • O'Gorman L; Universitätsklinikum Tübingen - Institut für Medizinische Genetik und angewandte Genomik, Tübingen, Germany.
  • Corominas-Galbany J; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Yaldiz B; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Steyaert W; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • de Boer E; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Vissers LELM; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Kamsteeg EJ; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Pfundt R; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
  • Swinkels H; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • den Ouden A; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
  • Te Paske IBAW; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • de Voer RM; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
  • Faivre L; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Denommé-Pichon AS; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Duffourd Y; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Vitobello A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Chevarin M; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Straub V; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Töpf A; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
  • van der Kooi AJ; Centre de Référence Maladies Rares "Anomalies du développement et syndromes malformatifs", Centre de Génétique, FHU-TRANSLAD et Institut GIMI, CHU Dijon Bourgogne, Dijon, France.
  • Magrinelli F; UMR1231-Inserm, Génétique des Anomalies du développement, Université de Bourgogne Franche-Comté, Dijon, France.
  • Rocca C; Laboratoire de Génétique chromosomique et moléculaire, UF6254 Innovation en diagnostic génomique des maladies rares, Centre Hospitalier Universitaire de Dijon, Dijon, France.
  • Hanna MG; UMR1231-Inserm, Génétique des Anomalies du développement, Université de Bourgogne Franche-Comté, Dijon, France.
  • Vandrovcova J; Laboratoire de Génétique chromosomique et moléculaire, UF6254 Innovation en diagnostic génomique des maladies rares, Centre Hospitalier Universitaire de Dijon, Dijon, France.
  • Ossowski S; Laboratoire de Génétique chromosomique et moléculaire, UF6254 Innovation en diagnostic génomique des maladies rares, Centre Hospitalier Universitaire de Dijon, Dijon, France.
  • Laurie S; UMR1231-Inserm, Génétique des Anomalies du développement, Université de Bourgogne Franche-Comté, Dijon, France.
  • Gilissen C; Laboratoire de Génétique chromosomique et moléculaire, UF6254 Innovation en diagnostic génomique des maladies rares, Centre Hospitalier Universitaire de Dijon, Dijon, France.
Eur J Hum Genet ; 32(2): 200-208, 2024 Feb.
Article en En | MEDLINE | ID: mdl-37853102
Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations of genetic testing methods. Various bioinformatic tools have been developed to identify MEIs in Next Generation Sequencing data. However, most tools have been developed specifically for genome sequencing (GS) data rather than exome sequencing (ES) data, which remains more widely used for routine diagnostic testing. In this study, we benchmarked six MEI detection tools (ERVcaller, MELT, Mobster, SCRAMble, TEMP2 and xTea) on ES data and on GS data from publicly available genomic samples (HG002, NA12878). For all the tools we evaluated sensitivity and precision of different filtering strategies. Results show that there were substantial differences in tool performance between ES and GS data. MELT performed best with ES data and its combination with SCRAMble increased substantially the detection rate of MEIs. By applying both tools to 10,890 ES samples from Solve-RD and 52,624 samples from Radboudumc we were able to diagnose 10 patients who had remained undiagnosed by conventional ES analysis until now. Our study shows that MELT and SCRAMble can be used reliably to identify clinically relevant MEIs in ES data. This may lead to an additional diagnosis for 1 in 3000 to 4000 patients in routine clinical ES.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Raras / Exoma Límite: Humans Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Raras / Exoma Límite: Humans Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos