1. Development of a new expanded next‐generation sequencing panel for genetic diseases involved in dyslipidemia
- Author
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Philippe Moulin, Igor Tauveron, Mathilde Di Filippo, Christophe Marçais, Chantal Jacobs, Alexandre Janin, Anne-Sophie Wozny, O. Marmontel, X. Vanhoye, Sabrina Dumont, Pierre Poinsot, Thomas Simonet, Cyrielle Caussy, Gilles Millat, Muriel Mahl, Nicolas Chatron, Sybil Charrière, Delphine Collin-Chavagnac, Noël Peretti, Claire Bardel, Pierre Antoine Rollat-Farnier, Séverine Nony, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Hospices Civils de Lyon
- Subjects
Male ,0301 basic medicine ,Candidate gene ,DNA Copy Number Variations ,Computational biology ,030105 genetics & heredity ,Biology ,genetic risk score ,DNA sequencing ,03 medical and health sciences ,Exon ,molecular diagnosis ,Genetics ,medicine ,Humans ,copy number variant ,Genetic Testing ,Copy-number variation ,Genetic risk ,Gene ,Genetics (clinical) ,Dyslipidemias ,hypercholesterolemia ,dyslipidemia ,Genetic Diseases, Inborn ,High-Throughput Nucleotide Sequencing ,hypobetalipoproteinemia ,Sequence Analysis, DNA ,medicine.disease ,030104 developmental biology ,targeted next generation sequencing ,Female ,Dyslipidemia ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; The aim of this study was to provide an efficient tool: reliable, able to increase the molecular diagnosis performance, to facilitate the detection of copy number variants (CNV), to assess genetic risk scores (wGRS) and to offer the opportunity to explore candidate genes. Custom SeqCap EZ libraries, NextSeq500 sequencing and a homemade pipeline enable the analysis of 311 dyslipidemia-related genes. In the training group (48 DNA from patients with a well-established molecular diagnosis), this next-generation sequencing (NGS) workflow showed an analytical sensitivity >99% (n = 532 variants) without any false negative including a partial deletion of one exon. In the prospective group, from 25 DNA from patients without prior molecular analyses, 18 rare variants were identified in the first intention panel genes, allowing the diagnosis of monogenic dyslipidemia in 11 patients. In six other patients, the analysis of minor genes and wGRS determination provided a hypothesis to explain the dyslipidemia. Remaining data from the whole NGS workflow identified four patients with potentially deleterious variants. This NGS process gives a major opportunity to accede to an enhanced understanding of the genetic of dyslipidemia by simultaneous assessment of multiple genetic determinants.
- Published
- 2020