Actionable Genes, Core Databases, and Locus-Specific Databases

Autor: Arnaud Blanchard, Sylviane Olschwang, Christophe Béroud, Catherine Boileau, Martin Krahn, Aurélie Fabre, Jean-Pierre Desvignes, Morgane Miltgen, Pauline Arnaud, Amélie Pinard, David Salgado, Philippe Grandval, Stéphane Zaffran, Gwenaëlle Collod-Béroud, Laura Barre, Hélène Mathieu
Přispěvatelé: Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de reference national pour le syndrome de Marfan et apparentés, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Oncologie [Hôpital Clairval - Marseille], Hôpital Privé Clairval [Marseille], Hôpital Européen [Fondation Ambroise Paré - Marseille], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), APHP Service de Génétique, Hôpital Bichat, Université Paris Diderot - Paris 7 (UPD7), Gall, Valérie
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Human Mutation
Human Mutation, Wiley, 2016, 37 (12, SI), pp.1299-1307. ⟨10.1002/humu.23112⟩
Human Mutation, 2016, 37 (12, SI), pp.1299-1307. ⟨10.1002/humu.23112⟩
ISSN: 1059-7794
1098-1004
DOI: 10.1002/humu.23112⟩
Popis: International audience; Adoption of next-generation sequencing (NGS) in a diagnostic context raises numerous questions with regard to identification and reports of secondary variants (SVs) in actionable genes. To better understand the whys and wherefores of these questioning, it is necessary to understand how they are selected during the filtering process and how their proportion can be estimated. It is likely that SVs are underestimated and that our capacity to label all true SVs can be improved. In this context, Locus-specific databases (LSDBs) can be key by providing a wealth of information and enabling classifying variants. We illustrate this issue by analyzing 318 SVs in 23 actionable genes involved in cancer susceptibility syndromes identified through sequencing of 572 participants selected for a range of atherosclerosis phenotypes. Among these 318 SVs, only 43.4% are reported in Human Gene Mutation Database (HGMD) Professional versus 71.4% in LSDB. In addition, 23.9% of HGMD Professional variants are reported as pathogenic versus 4.8% for LSDB. These data underline the benefits of LSDBs to annotate SVs and minimize overinterpretation of mutations thanks to their efficient curation process and collection of unpublished data. (C) 2016 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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