Search

Your search keyword '"PORCHET, Nathalie"' showing total 5 results
Start Over Author "PORCHET, Nathalie"
5 results on '"PORCHET, Nathalie"'

1. Detection of copy-number variations from NGS data using read depth information: a diagnostic performance evaluation

Author

Anne-Claire Richard, Anne Rovelet-Lecrux, Dominique Campion, Sophie Coutant, Kilan Le Guennec, Jean-François Deleuze, Gaëlle Bougeard, Mathieu Castelain, Nathalie Drouot, Pascal Chambon, Stéphanie Vasseur, Thierry Frebourg, Jacqueline Bou, François Lecoquierre, Anne Boland, Géraldine Joly-Helas, Kévin Cassinari, Gaël Nicolas, Stéphane Rousseau, Steeve Fourneaux, Gwendoline Lienard, Edwige Kasper, Myriam Vezain, Pascale Saugier-Veber, Isabelle Tournier, Nathalie Le Meur, Olivier Quenez, Françoise Charbonnier, Emilie Bouvignies, Virginie N'Guyen-Viet, Stéphanie Baert-Desurmont, Sandrine Manase, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier du Rouvray, PORCHET, Nathalie, Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
DNA Copy Number Variations, Computer science, [SDV]Life Sciences [q-bio], Read depth, Computational biology, Sensitivity and Specificity, Article, Workflow, 03 medical and health sciences, 0302 clinical medicine, Gene panel, Exome Sequencing, Multiplex polymerase chain reaction, Genetics, Humans, Genetic Testing, Copy-number variation, Exome, Genetics (clinical), 030304 developmental biology, Comparative Genomic Hybridization, 0303 health sciences, High-Throughput Nucleotide Sequencing, Predictive value, [SDV] Life Sciences [q-bio], Multiplex Polymerase Chain Reaction, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract

International audience; The detection of copy-number variations (CNVs) from NGS data is underexploited as chip-based or targeted techniques are still commonly used. We assessed the performances of a workflow centered on CANOES, a bioinformatics tool based on read depth information. We applied our workflow to gene panel (GP) and whole-exome sequencing (WES) data, and compared CNV calls to quantitative multiplex PCR of short fluorescent fragments (QMSPF) or array comparative genomic hybridization (aCGH) results. From GP data of 3776 samples, we reached an overall positive predictive value (PPV) of 87.8%. This dataset included a complete comprehensive QMPSF comparison of four genes (60 exons) on which we obtained 100% sensitivity and specificity. From WES data, we first compared 137 samples with aCGH and filtered comparable events (exonic CNVs encompassing enough aCGH probes) and obtained an 87.25% sensitivity. The overall PPV was 86.4% following the targeted confirmation of candidate CNVs from 1056 additional WES. In addition, our CANOES-centered workflow on WES data allowed the detection of CNVs with a resolution of single exons, allowing the detection of CNVs that were missed by aCGH. Overall, switching to an NGS-only approach should be cost-effective as it allows a reduction in overall costs together with likely stable diagnostic yields. Our bioinformatics pipeline is available at: https://gitlab.bioinfo-diag.fr/nc4gpm/canoes-centered-workflow.

Published
2020
Full Text
View/download PDF

2. Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use

Author

Husson, Thomas, Lecoquierre, François, Cassinari, Kevin, Charbonnier, Camille, Quenez, Olivier, Goldenberg, Alice, Guerrot, Anne-Marie, Richard, Anne-Claire, Drouin-Garraud, Valérie, Brehin, Anne-Claire, Soleimani, Maryam, Taton, Romain, Rotharmel, Maud, Rosier, Antoine, Chambon, Pascal, Le Meur, Nathalie, Joly-Helas, Géraldine, Saugier-Veber, Pascale, Boland, Anne, Deleuze, Jean-François, Olaso, Robert, Frebourg, Thierry, Nicolas, Gael, Guillin, Olivier, Campion, Dominique, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de Psychopathologie et Processus de Santé (LPPS - EA 4057), Université Paris Descartes - Paris 5 (UPD5), Centre de Ressources Autisme de Haute Normandie (CRAHN), Centre de Ressources Autisme de Haute Normandie, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurologie [Rouen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and PORCHET, Nathalie

Subjects
DNA Copy Number Variations, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], High-Throughput Nucleotide Sequencing, Autism spectrum disorders, Article, lcsh:RC321-571, [SDV] Life Sciences [q-bio], Exome Sequencing, mental disorders, Humans, Genetic Predisposition to Disease, Clinical genetics, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Abstract

International audience; Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component whose knowledge evolves quickly. Next-generation sequencing is the only effective technology to deal with the high genetic heterogeneity of ASD in a clinical setting. However, rigorous criteria to classify rare genetic variants conferring ASD susceptibility are currently lacking. We have performed whole-exome sequencing to identify both nucleotide variants and copy number variants (CNVs) in 253 ASD patients, including 68 patients with intellectual disability (ID) and 90 diagnosed as Asperger syndrome. Using explicit criteria to classify both susceptibility genes and susceptibility variants we prioritized 217 genes belonging to the following categories: syndromic genes, genes with an excess of de novo protein truncating variants and genes targeted by rare CNVs. We obtained a susceptibility variant detection rate of 19.7% (95% CI: [15–25.2%]). The rate for CNVs was 7.1% (95% CI: [4.3–11%]) and 12.6% (95% CI: [8.8–17.4%]) for nucleotide variants. The highest rate (30.1%, 95% CI: [20.2–43.2%]) was obtained in the ASD + ID subgroup. A strong contributor for at risk nucleotide variants was the recently identified set of genes (n = 81) harboring an excess of de novo protein truncating variants. Since there is currently no evidence that the genes targeted here are necessary and sufficient to cause ASD, we recommend to avoid the term “causative of ASD” when delivering the information about a variant to a family and to use instead the term “genetic susceptibility factor contributing to ASD”.

Published
2020
Full Text
View/download PDF

3. Searching for secondary findings: considering actionability and preserving the right not to know

Author

Delphine Dupin-Deguine, Jean-Paul Bonnefont, Catherine Bourgain, Bertrand Isidor, Paul-Loup Weil-Dubuc, Julie Plaisancié, Franck Bourdeaut, Eric Bieth, Laurent Pasquier, Nicolas Chassaing, Kym M. Boycott, Sophie Julia, Benjamin Cogné, Nadège Corradini, Pascale Saugier-Veber, Delphine Héron, Arnold Munnich, Damien Haye, Marie Vincent, Mathilde Nizon, Mauro Turrini, Sylvie Manouvrier, Stéphane Bézieau, Patrick Calvas, Cyril Mignot, Danya F. Vears, PORCHET, Nathalie, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Excellence Laboratory LabEx DISTALZ, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Pédiatrique [CHU Nantes], Hôpital Mère-Enfant, CHU de Nantes, Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], University of Ottawa [Ottawa], Université Paris 1 Panthéon-Sorbonne - UFR Philosophie (UP1 UFR10), Université Paris 1 Panthéon-Sorbonne (UP1), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Melbourne, Murdoch Children's Research Institute (MCRI), Laboratoire de Génétique Moléculaire, CHU Toulouse [Toulouse], Département de Génétique (CHU Necker - Enfants Malades [AP-HP] ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service de génétique médicale, Service de génétique clinique, hôpital Sud, Groupe de recherche clinique 'déficience intellectuelle et autisme', and Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Genetics, Medical, [SDV]Life Sciences [q-bio], MEDLINE, Truth Disclosure, 03 medical and health sciences, Viewpoint, Genetics, Humans, Genetic Predisposition to Disease, Genetic Testing, Genetics (clinical), Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Information retrieval, Genome, Human, 030305 genetics & heredity, Genomics, 16. Peace & justice, Europe, [SDV] Life Sciences [q-bio], Practice Guidelines as Topic, Psychology, Medical ethics
Abstract

International audience; No abstract available

Published
2019
Full Text
View/download PDF

4. Identification of potential genetic risk factors for bipolar disorder by whole-exome sequencing

Author

Husson, Thomas, Duboc, Jean-Baptiste, Quenez, Olivier, Charbonnier, Camille, Rotharmel, Maud, Cuenca, Macarena, Jegouzo, Xavier, Richard, Anne-Claire, Frebourg, Thierry, Deleuze, Jean-François, Boland, Anne, Genin, Emmanuelle, Debette, Stéphanie, Tzourio, Christophe, Campion, Dominique, Nicolas, Gaël, Guillin, Olivier, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Research, Centre hospitalier du Rouvray, Sotteville-lès-Rouen, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and PORCHET, Nathalie

Subjects
Adult, Aged, 80 and over, Male, Bipolar Disorder, Adolescent, [SDV]Life Sciences [q-bio], Mutation, Missense, Middle Aged, Article, White People, [SDV] Life Sciences [q-bio], Young Adult, Gene Frequency, Risk Factors, Exome Sequencing, Humans, Female, Genetic Predisposition to Disease, France, Aged
Abstract

International audience; This study aims at assessing the burden of rare (minor allele frequency

Published
2018
Full Text
View/download PDF

5. Somatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer's disease

Author

Dominique Campion, Colin Smith, Manon S. Oud, Safa Al Sarraj, Stefan H. Lelieveld, Gaël Nicolas, Anne-Claire Richard, Florent Marguet, Christian Gilissen, Thierry Frebourg, Alexander Hoischen, Joris A. Veltman, Rocio Acuna-Hidalgo, Didier Hannequin, Stéphane Rousseau, Patrick F. Chinnery, Olivier Quenez, Olaf Ansorge, Christopher Morris, Annie Laquerrière, Michael J. Keogh, Johannes Attems, David Wallon, Marloes Steehouwer, Chinnery, Patrick [0000-0002-7065-6617], Apollo - University of Cambridge Repository, PORCHET, Nathalie, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radboud University Medical Center [Nijmegen], Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), Department of Human Genetics [Nijmegen], Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Building Research Establishment (BRE/Edinburgh), University of Edinburgh, John Radcliffe Hospital [Oxford University Hospital], King‘s College London, Department of Research, Centre hospitalier du Rouvray, Sotteville-lès-Rouen, France, Service de neurologie [Rouen], Mitochondrial Research Group, University of Northumbria at Newcastle [United Kingdom], and Department of Pathology, Rouen University Hospital

Subjects
0301 basic medicine, Post‐zygotic, Adult, Male, Epidemiology, Somatic cell, [SDV]Life Sciences [q-bio], SORL1, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Biology, medicine.disease_cause, Deep sequencing, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Developmental Neuroscience, Alzheimer Disease, PSEN2, medicine, PSEN1, Humans, Genetic Predisposition to Disease, Prion‐like, Allele, Prion-like, Aged, Genes, Dominant, Genetics, Mutation, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Mosaicism, Post-zygotic, Health Policy, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Amplicon, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, 030104 developmental biology, Alzheimer, Female, Neurology (clinical), Geriatrics and Gerontology, 030217 neurology & neurosurgery
Abstract

Introduction A minority of patients with sporadic early-onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP , PSEN1 , or PSEN2 . We hypothesized that negatively screened patients may harbor somatic variants in these genes. Methods We applied an ultrasensitive approach based on single-molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic patients with AD (>80% exhibited an early onset, Results We identified and confirmed nine somatic variants (allele fractions: 0.2%–10.8%): two APP , five SORL1 , one NCSTN , and one MARK4 variant by independent amplicon-based deep sequencing. Discussion Two of the SORL1 variant might have contributed to the disease, the two APP variants were interpreted as likely benign and the other variants remained of unknown significance. Somatic variants in the autosomal dominant AD genes may not be a common cause of sporadic AD, including early onset cases.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results