Descriptor: "SDV:GEN" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"SDV:GEN"' showing total 16 results

Start Over Descriptor "SDV:GEN"

16 results on '"SDV:GEN"'

1. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments

Author: Anne Claude Tabet, Françoise Devillard, Christelle M. Durand, Dominique Bonneau, Caroline Schluth-Bolard, Hugo Peyre, Frédérique Amsellem, Jennifer L. Howe, Brigitte Assouline, Laurence Perrin, Patrick Edery, Gudrun A. Rappold, Alexis Brice, Tobias M. Boeckers, Kevin Mouzat, Mary Coleman, Diana Zelenika, Guy A. Rouleau, Christel Depienne, Alexandra Afenjar, Pilar Galan, Peter Szatmari, Coline Stordeur, Fabienne Giuliano, Thomas Bourgeron, Delphine Héron, Anthony P. Monaco, Aurélia Jacquette, Marion Leboyer, Elena Maestrini, Roberto Toro, Anne Polge, Serge Lumbroso, Richard Delorme, Maria Råstam, François Rivier, Richard Holt, Stephen W. Scherer, Jessica Guibert, Elodie Ey, Dalila Pinto, Christopher Gillberg, Béatrice Regnault, Fanny Laffargue, Claire S. Leblond, Julie Gauthier, Nathalie Lemière, James Lespinasse, Alexandre Mathieu, Michael J. Schmeisser, Jean Chiesa, Agnès Rastetter, Marc Delepine, Catalina Betancur, I. Carina Gillberg, Daisuke Sato, Mark Lathrop, Caroline Nava, Damien Sanlaville, Guillaume Huguet, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratoire de diagnotic moléculaire, CHU Sainte Justine [Montréal], Service de génétique médicale, Hôpital l'Archet, Service de Psychiatrie de l'Enfant et de l'Adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Department of Clinical Sciences, Lund University [Lund], Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Department of Molecular Human Genetics, Universität Heidelberg [Heidelberg] = Heidelberg University, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-Hôpital Couple-Enfant, Unité Pédopsychiatrique et Neuropédiatrique de Diagnostic et d'Evaluation des Troubles Envahissants du Développement, Centre Alpin de DIagnostic Précoce de l'Autisme - CADIPA-Centre Hospitalier Alpes Isère, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, Laboratoire de Cytogénétique, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Génotypage des Eucaryotes (Plate-Forme), Institut Pasteur [Paris] (IP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut for Anatomy and Cell Biology, Universität Ulm - Ulm University [Ulm, Allemagne], Foundation for Autism Research, Center of Excellence in Neuroscience, CHU de Montréal, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institute of Child Health, University College of London [London] (UCL), This work was funded by the Institut Pasteur, CNRS, INSERM, AP-HP, University Paris Diderot, the Bettencourt-Schueller foundation, the Orange foundation, the FondaMental foundation, the Conny-Maeva foundation, the Cognacq-Jay foundation, the ANR (ANR-08-MNPS-037-01 - SynGen), Neuron- ERANET (EUHF-AUTISM), the DFG (BO1718/3-1, 4-1) and Baustein L.SBN.0081., Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, Stordeur C, Depienne C, Mouzat K, Pinto D, Howe J, Lemière N, Durand CM, Guibert J, Ey E, Toro R, Peyre H, Mathieu A, Amsellem F, Rastam M, Gillberg IC, Rappold GA, Holt R, Monaco AP, Maestrini E, Galan P, Heron D, Jacquette A, Afenjar A, Rastetter A, Brice A, Devillard F, Assouline B, Laffargue F, Lespinasse J, Chiesa J, Rivier F, Bonneau D, Regnault B, Zelenika D, Delepine M, Lathrop M, Sanlaville D, Schluth-Bolard C, Edery P, Perrin L, Tabet AC, Schmeisser MJ, Boeckers TM, Coleman M, Sato D, Szatmari P, Scherer SW, Rouleau GA, Betancur C, Leboyer M, Gillberg C, Delorme R, Bourgeron T, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg], University of Oxford [Oxford], Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), and Betancur, Catalina
Subjects: Male, Cancer Research, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, GENE DELETION, 0302 clinical medicine, Cognition, Intellectual disability, Child, Genetics (clinical), Genetics, Psychiatry, Neurons, 0303 health sciences, Mutation, SDV:GEN, META-ANALYSIS, Penetrance, Hypotonia, 3. Good health, SHANK2, Autism spectrum disorder, Female, medicine.symptom, Research Article, lcsh:QH426-470, DNA Copy Number Variations, Nerve Tissue Proteins, Biology, 03 medical and health sciences, Intellectual Disability, mental disorders, medicine, Humans, Clinical significance, AUTISM, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Biology and Life Sciences, Human Genetics, medicine.disease, lcsh:Genetics, Child Development Disorders, Pervasive, Case-Control Studies, Synapses, Autism, Cognition Disorders, 030217 neurology & neurosurgery
Abstract: SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability—more than 1 in 50—warrant its consideration for mutation screening in clinical practice., Author Summary Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Mutations altering genes involved in the junction between brain cells have been repeatedly associated in ASD. For example, SHANK1, SHANK2 and SHANK3 emerged as one family of genes that are associated with ASD. However, little was known about the number of patients carrying these mutations and the clinical outcome. Here, we performed a new genetic screen of SHANK mutations and these results were analyzed in combination with those of the literature. In summary, SHANK mutations account for ∼1% of patients with ASD and were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. Given the high frequency and impact of SHANK3 mutations in individuals with ASD and intellectual disability—more than 1 in 50—this gene should be screened for mutations in clinical practice.
Published: 2014
Full Text: View/download PDF

2. The Past, Present, and Future of Immune Repertoire Biology - The Rise of Next-Generation Repertoire Analysis

Author: Adrien eSix, Encarnita eMariotti-Ferrandiz, Wahiba eChaara, Susana eMagadan, Hang-Phuong ePham, Marie-Paule eLefranc, Thierry eMora, Véronique eThomas-Vaslin, Aleksandra M. Walczak, Pierre eBoudinot, Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique de l'ENS [École Normale Supérieure] (LPTENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, Centre d’Investigation Clinique en Biothérapies [CHU Pitié-Salpêtrière] (CIC-BT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [APHP], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique de l'ENS (LPTENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: lcsh:Immunologic diseases. Allergy, [SDV.IMM] Life Sciences [q-bio]/Immunology, Sequence analysis, Immunology, Review Article, Computational biology, Biology, CDR3 Spectratyping, diversity analysis, DNA sequencing, modelling, 03 medical and health sciences, 0302 clinical medicine, Repertoire analysis, Immunologie, Immunology and Allergy, gene nomenclature, immune receptors, 030304 developmental biology, Genetics, 0303 health sciences, B cell repertoire, Repertoire, modeling, SDV:GEN, Gene nomenclature, Diversity analysis, statistics, Complementarity (molecular biology), [SDV.IMM]Life Sciences [q-bio]/Immunology, next-generation sequencing, lcsh:RC581-607, T cell repertoire, 030215 immunology
Abstract: International audience; T and B cell repertoires are collections of lymphocytes, each characterized by its antigen-specific receptor. We review here classical technologies and analysis strategies developed to assess immunoglobulin (IG) and T cell receptor (TR) repertoire diversity, and describe recent advances in the field. First, we describe the broad range of available methodolog-ical tools developed in the past decades, each of which answering different questions and showing complementarity for progressive identification of the level of repertoire alterations: global overview of the diversity by flow cytometry, IG repertoire descriptions at the protein level for the identification of IG reactivities, IG/TR CDR3 spectratyping strategies, and related molecular quantification or dynamics of T/B cell differentiation. Additionally, we introduce the recent technological advances in molecular biology tools allowing deeper analysis of IG/TR diversity by next-generation sequencing (NGS), offering systematic and comprehensive sequencing of IG/TR transcripts in a short amount of time. NGS provides several angles of analysis such as clonotype frequency, CDR3 diversity, CDR3 sequence analysis, V allele identification with a quantitative dimension, therefore requiring high-throughput analysis tools development. In this line, we discuss the recent efforts made for nomenclature standardization and ontology development. We then present the variety of available statistical analysis and modeling approaches developed with regards to the various levels of diversity analysis, and reveal the increasing sophistication of those modeling approaches. To conclude, we provide some examples of recent mathematical modeling strategies and perspectives that illustrate the active rise of a " next-generation " of repertoire analysis.
Published: 2013
Full Text: View/download PDF

3. Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Author: Nancy Uhrchammer, Eliane Chouery, André Mégarbané, Dominique Stoppa-Lyonnet, Jinane Nassar-Slaba, Lisa Golmard, Nadine Jalkh, Nabiha Salem, Yves-Jean Bignon, 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 ), Département d'Oncogénétique, Institut National de la Recherche Agronomique ( INRA ) -Réseau National Alimentation Cancer Recherche (réseau NACRe)-Centre Jean Perrin (CJP-EA 4233), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Génétique Médicale, Université Saint-Joseph de Beyrouth ( USJ ) -Faculté de Médecine, 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 Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER-Institut National de la Recherche Agronomique (INRA)-Réseau National Alimentation Cancer Recherche (réseau NACRe), 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), Université Saint-Joseph de Beyrouth (USJ)-Faculté de Médecine, Institut National de la Recherche Agronomique (INRA)-Réseau National Alimentation Cancer Recherche (réseau NACRe)-Centre Jean Perrin (CJP-EA 4233), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Réseau National Alimentation Cancer Recherche (réseau NACRe)-Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, and BMC, Ed.
Subjects: Oncology, endocrine system diseases, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Gene, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Breast cancer, Familial, Family history, Lebanon, skin and connective tissue diseases, Genetics (clinical), Cancer, Genetics, 0303 health sciences, Mutation, education.field_of_study, Mutation Spectra, Family aggregation, SDV:GEN, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030220 oncology & carcinogenesis, medicine.medical_specialty, lcsh:QH426-470, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Malignancy, lcsh:RC254-282, 03 medical and health sciences, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, BRCA1, BRCA2, education, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, medicine.disease, lcsh:Genetics, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: Breast cancer is the most prevalent malignancy in women in Western countries, currently accounting for one third of all female cancers. Familial aggregation is thought to account for 5–10 % of all BC cases, and germline mutations in BRCA1 and BRCA2 account for less of the half of these inherited cases. In Lebanon, breast cancer represents the principal death-causing malignancy among women, with 50 % of the cases diagnosed before the age of 50 years. In order to study BRCA1/2 mutation spectra in the Lebanese population, 72 unrelated patients with a reported family history of breast and/or ovarian cancers or with an early onset breast cancer were tested. Fluorescent direct sequencing of the entire coding region and intronic sequences flanking each exon was performed. A total of 38 BRCA1 and 40 BRCA2 sequence variants were found. Seventeen of them were novel. Seven confirmed deleterious mutations were identified in 9 subjects providing a frequency of mutations of 12.5 %. Fifteen variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases. In conclusion, this study represents the first evaluation of the deleterious and unclassified genetic variants in the BRCA1/2 genes found in a Lebanese population with a relatively high risk of breast cancer.
Published: 2012
Full Text: View/download PDF

4. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut

Author: Nadine Cerf-Bensussan, Dominique Rainteau, François Taddei, Sabine Rakotobe, Marianne De Paepe, Valérie Gaboriau-Routhiau, Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Inflammation intestinale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Robustesse et évolvabilité de la vie (U1001), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), MDP was supported by the Fondation pour la Recherche Médicale (http://www.frm.org/)., Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Recherche Agronomique (INRA), Interactions de l'épithelium intestinal et du système immunitaire ( UMR_S 793 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Recherche Agronomique ( INRA ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Robustesse et évolvabilité de la vie ( U1001 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Autard, Delphine
Subjects: Operon, Mutant, Genetic Fitness, MESH: Escherichia coli Proteins, Mice, MESH : Selection, Genetic, MESH: Animals, 0303 health sciences, MESH : Trans-Activators, MESH: Escherichia coli, Escherichia coli Proteins, Microbiology and Parasitology, Bacterial, SDV:GEN, MESH: Transcription Factors, MESH : Multienzyme Complexes, Microbiologie et Parasitologie, MESH : Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Animals, Bacterial Outer Membrane Proteins, Bile Acids and Salts, Biodiversity, DNA-Binding Proteins, Escherichia coli, Flagella, Gastrointestinal Tract, Gene Expression Regulation, Immunity, Innate, Multienzyme Complexes, Mutation, Nutritional Physiological Phenomena, Phenotype, Selection, Genetic, Trans-Activators, Transcription Factors, MESH : DNA-Binding Proteins, MESH : Gene Expression Regulation, Bacterial, MESH: Phenotype, Microbiology, MESH: Flagella, MESH: Biodiversity, 03 medical and health sciences, Genetics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, Biology, Ecology, Evolution, Behavior and Systematics, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH : Genetic Fitness, 030306 microbiology, MESH: Bacterial Outer Membrane Proteins, Immunity, Innate, Colonisation, Regulon, MESH : Nutritional Physiological Phenomena, MESH: Gastrointestinal Tract, MESH : Gastrointestinal Tract, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Cancer Research, MESH : Escherichia coli, MESH : Transcription Factors, MESH: Selection, Genetic, [SDV.GEN] Life Sciences [q-bio]/Genetics, Gut flora, medicine.disease_cause, MESH: Multienzyme Complexes, MESH: Genetic Fitness, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Biodiversity, Genetics (clinical), 2. Zero hunger, Experimental evolution, MESH: Gene Expression Regulation, Bacterial, biology, MESH : Escherichia coli Proteins, MESH : Immunity, Innate, MESH: Immunity, Innate, MESH : Mutation, Research Article, MESH: Mutation, lcsh:QH426-470, MESH: Trans-Activators, MESH: Bile Acids and Salts, Model Organisms, MESH : Mice, medicine, Selection, Genetic, MESH: Nutritional Physiological Phenomena, MESH : Bacterial Outer Membrane Proteins, MESH: Mice, 030304 developmental biology, Evolutionary Biology, Gene Expression Regulation, Bacterial, biology.organism_classification, MESH : Bile Acids and Salts, lcsh:Genetics, bacteria, MESH : Animals, MESH : Flagella, MESH: DNA-Binding Proteins
Abstract: Bacterial diversification is often observed, but underlying mechanisms are difficult to disentangle and remain generally unknown. Moreover, controlled diversification experiments in ecologically relevant environments are lacking. We studied bacterial diversification in the mammalian gut, one of the most complex bacterial environments, where usually hundreds of species and thousands of bacterial strains stably coexist. Herein we show rapid genetic diversification of an Escherichia coli strain upon colonisation of previously germ-free mice. In addition to the previously described mutations in the EnvZ/OmpR operon, we describe the rapid and systematic selection of mutations in the flagellar flhDC operon and in malT, the transcriptional activator of the maltose regulon. Moreover, within each mouse, the three mutant types coexisted at different levels after one month of colonisation. By combining in vivo studies and determination of the fitness advantages of the selected mutations in controlled in vitro experiments, we provide evidence that the selective forces that drive E. coli diversification in the mouse gut are the presence of bile salts and competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence generates sympatric diversification of the gut microbiota. These results illustrate how experimental evolution in natural environments enables identification of both the selective pressures that organisms face in their natural environment and the diversification mechanisms., Author Summary The mechanisms generating the huge biodiversity on earth are not entirely understood. Bacterial populations are powerful models to explore the mechanisms of evolution, owing to their big population size, rapid growth, and high mutation rate. One of the more complex bacterial community is the mammalian gut microbiota, and Escherichia coli is one of the first colonizers of the newborn intestine. Herein we studied diversification of an Escherichia coli strain in germ-free mice, a simplified though ecologically relevant system. We show rapid genetic diversification upon colonization, characterized by the systematic selection of mutations in three different pathways: in the global regulator EnvZ/OmpR controlling outer membrane permeability, in the flagellar operon, and in the maltose regulon. By combining in vivo and in vitro experiments, we show that the selective forces that drive E. coli diversification are the presence of bile salts and the competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence is sufficient to mediate diversification of bacteria. These results illustrate how experimental evolution in natural environments allows the identification of the selective pressures that organisms face in their natural environment, as well as the diversification mechanisms.
Published: 2011
Full Text: View/download PDF

5. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

Author: John M. Cullen, Jérôme Abadie, Catherine André, Matthew Breen, B. Hedan, Rachael Thomas, Alison A. Motsinger-Reif, Department of Molecular Biomedical Sciences, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC)-College of Veterinary Medicine Raleigh, Center for Comparative Medicine and Translational Research, University of North Carolina System (UNC)-University of North Carolina System (UNC), Bioinformatics Research Center, Department of Statistics, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Department of Population Health and Pathobiology, Lineberger Comprehensive Cancer Center, University of North Carolina [Chapel Hill] (UNC), This study was supported by funds from the American Kennel Club Canine Health Foundation (award numbers 2667 and 760 [MB and JC] and 336b/ 337 [CA])., Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Lineberger Comprehensive Cancer Center (UNC Lineberger), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and De Villemeur, Hervé
Subjects: Male, Cancer Research, Penetrance, [SDV.GEN] Life Sciences [q-bio]/Genetics, Histiocytic sarcoma, 0403 veterinary science, Loss of heterozygosity, CDKN2A, Immunologie, Genes, Tumor Suppressor, Cancer, Genetics, 0303 health sciences, education.field_of_study, Comparative Genomic Hybridization, medicine.diagnostic_test, SDV:GEN, 04 agricultural and veterinary sciences, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, Cytogenetic Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, DNA Copy Number Variations, 040301 veterinary sciences, Immunology, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, lcsh:RC254-282, 03 medical and health sciences, Dogs, [SDV.CAN] Life Sciences [q-bio]/Cancer, Canine Histiocytic Sarcoma, medicine, PTEN, Animals, Genetic Predisposition to Disease, education, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genes, p16, PTEN Phosphohydrolase, medicine.disease, Disease Models, Animal, Cancer research, biology.protein, Histiocytic Sarcoma, Gene Deletion, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract: Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model for the human counterpart, providing additional evidence towards elucidation of the pathophysiological and genetic mechanisms associated with histiocytic malignancies. Extrapolation of data derived from canine histiocytic disorders to human histiocytic proliferation may help to further our understanding of the propagation and cancerization of histiocytic cells, contributing to development of new and effective therapeutic modalities for both species.
Published: 2011
Full Text: View/download PDF

6. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers

Author: G. Diane Shelton, Susan M. Taylor, Alan H. Beggs, Johann Böhm, Katie M. Minor, Laurent Tiret, Marie Maurer, Andrew P. Mizisin, Ling T. Guo, Elizabeth C R Snead, Jocelyn Laporte, James R. Mickelson, M. Kozlowski, Martin K. Childers, Christophe Hitte, Anna Buj-Bello, Manton Center for Orphan Disease Research, Harvard Medical School [Boston] (HMS)-Boston Children's Hospital, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Western College of Veterinary Medicine, University of Saskatchewan [Saskatoon] (U of S), Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), School of Veterinary Medicine, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Wake Forest University, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Généthon, University of Minnesota [Twin Cities], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Genethon, Boston Children's Hospital-Harvard Medical School [Boston] (HMS), De Villemeur, Hervé, École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology [Univ California San Diego] (UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), and University of California (UC)-University of California (UC)
Subjects: Male, Pathology, Myotubularin, necklace fibers, canine myopathy, [SDV.GEN] Life Sciences [q-bio]/Genetics, Exon, Mice, 0302 clinical medicine, congenital myopathy, Chlorocebus aethiops, Missense mutation, Dog Diseases, Fluorescent Antibody Technique, Indirect, Genetics, Mice, Knockout, 0303 health sciences, Multidisciplinary, Genetic Diseases, X-Linked, SDV:GEN, Biological Sciences, myotubularin, animal model, Protein Tyrosine Phosphatases, Non-Receptor, X-linked myotubular myopathy, Muscle atrophy, Pedigree, COS Cells, Female, medicine.symptom, Myopathies, Structural, Congenital, medicine.medical_specialty, Genotype, Green Fluorescent Proteins, Molecular Sequence Data, Biology, 03 medical and health sciences, Dogs, Genetic model, medicine, Animals, Humans, Amino Acid Sequence, Centronuclear myopathy, Muscle, Skeletal, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Base Sequence, Sequence Homology, Amino Acid, medicine.disease, Congenital myopathy, Microscopy, Electron, Haplotypes, Mutation, 030217 neurology & neurosurgery
Abstract: Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy. Seven male Labrador Retrievers, age 14–26 wk, were clinically evaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size, centrally placed nuclei resembling fetal myotubes, and subsarcolemmal ringed and central dense areas highlighted with mitochondrial specific reactions. Ultrastructural studies confirmed the centrally located nuclei, abnormal perinuclear structure, and mitochondrial accumulations. Wild-type triads were infrequent, with most exhibiting an abnormal orientation of T tubules. MTM1 gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population. Analysis of a worldwide panel of 237 unaffected Labrador Retrievers and 59 additional control dogs from 25 other breeds failed to identify this variant, supporting it as the pathogenic mutation. Myotubularin protein levels and localization were abnormal in muscles from affected dogs, and expression of GFP-MTM1 p.N155K in COS-1 cells showed that the mutant protein was sequestered in proteasomes, where it was presumably misfolded and prematurely degraded. These data demonstrate that XLMTM in Labrador Retrievers is a faithful genetic model of the human condition.
Published: 2010
Full Text: View/download PDF

7. Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers

Author: Alain Lachaux, Emile Levy, Lise Bouthillier, Agnès Sassolas, Sylvie Labarge, Mathilde Charcosset, Philippe Moulin, Noël Peretti, Colette Deslandres, Justine Castagnetti, Claude C. Roy, Laurence Pugnet-Chardon, Department of Nutrition, CHU Sainte-Justine Research Center, Service de nutrition-hépato gastroentérologie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UF Dyslipidemia Laboratory, Hospices Civils de Lyon (HCL)-Hôpital Neurologique et Cardilogique, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Pediatrics, This study was supported by the Canadian Institutes of Health Research (EL, MOP 10584) and the J.A. de Sève Research Chair in Nutrition (EL). Dr. Peretti's fellowship was supported by a Lavoisier grant from the French Ministry of Foreign Affairs., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal]-Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Pediatrics, MESH: Vitamin E Deficiency, Lipid Metabolism Disorders, lcsh:Medicine, Review, [SDV.GEN] Life Sciences [q-bio]/Genetics, Cohort Studies, MESH: Lipid Metabolism Disorders, 0302 clinical medicine, MESH: Child, Chylomicrons, Genetics(clinical), Pharmacology (medical), Vitamin E Deficiency, Child, MESH: Cohort Studies, Genetics (clinical), Growth Disorders, 2. Zero hunger, Medicine(all), 0303 health sciences, biology, Anthropometry, Fatty Acids, General Medicine, SAR1B, SDV:GEN, MESH: Growth Disorders, MESH: Infant, 3. Good health, MESH: Chylomicrons, MESH: Fatty Acids, MESH: Malabsorption Syndromes, MESH: Diarrhea, Child, Preschool, Failure to thrive, Female, Vitamin E deficiency, medicine.symptom, MESH: Malnutrition, Chylomicron retention disease, Adult, Diarrhea, medicine.medical_specialty, MESH: Mutation, MESH: Monomeric GTP-Binding Proteins, MESH: Nervous System Diseases, 03 medical and health sciences, Malabsorption Syndromes, MESH: Anthropometry, Internal medicine, medicine, Humans, Preschool, 030304 developmental biology, Monomeric GTP-Binding Proteins, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, business.industry, Infant, Malnutrition, Mutation, Nervous System Diseases, lcsh:R, MESH: Child, Preschool, Abetalipoproteinemia, MESH: Adult, medicine.disease, MESH: Male, Hypocholesterolemia, Endocrinology, biology.protein, Hypobetalipoproteinemia, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined. The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience. The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation. Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications.
Published: 2010
Full Text: View/download PDF

8. Small variable segments constitute a major type of diversity of bacterial genomes at the species level

Author: Erick Denamur, Valérie Barbe, Marie-Agnès Petit, Meriem El Karoui, Claudine Médigue, Fabrice Touzain, BMC, Ed., MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Ecologie et Evolution des Microorganismes (EEM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: DNA, Bacterial, Staphylococcus aureus, Amino Acid Sequence, Base Sequence, DNA, Bacterial, Escherichia coli, Genetic Variation, Genome, Molecular Sequence Data, Species Specificity, Streptococcus pyogenes, Locus (genetics), Bacterial genome size, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Amino Acid Sequence, Biology, MESH: Base Sequence, MESH: Genome, Bacterial, 03 medical and health sciences, Genomic island, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetic variation, MESH: Staphylococcus aureus, MESH: Species Specificity, MESH: Genetic Variation, Gene, 030304 developmental biology, Genetics, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Molecular Sequence Data, MESH: Escherichia coli, Research, 030302 biochemistry & molecular biology, SDV:GEN, SDV:BBM:GTP, respiratory system, Phenotype, Pathogenicity island, MESH: DNA, Bacterial, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], human activities, MESH: Streptococcus pyogenes, Genome, Bacterial
Abstract: Comparison of all available genomes of three bacterial species suggests that a large part of genome diversity is contributed by short regions., Background Analysis of large scale diversity in bacterial genomes has mainly focused on elements such as pathogenicity islands, or more generally, genomic islands. These comprise numerous genes and confer important phenotypes, which are present or absent depending on strains. We report that despite this widely accepted notion, most diversity at the species level is composed of much smaller DNA segments, 20 to 500 bp in size, which we call microdiversity. Results We performed a systematic analysis of the variable segments detected by multiple whole genome alignments at the DNA level on three species for which the greatest number of genomes have been sequenced: Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes. Among the numerous sites of variability, 62 to 73% were loci of microdiversity, many of which were located within genes. They contribute to phenotypic variations, as 3 to 6% of all genes harbor microdiversity, and 1 to 9% of total genes are located downstream from a microdiversity locus. Microdiversity loci are particularly abundant in genes encoding membrane proteins. In-depth analysis of the E. coli alignments shows that most of the diversity does not correspond to known mobile or repeated elements, and it is likely that they were generated by illegitimate recombination. An intriguing class of microdiversity includes small blocks of highly diverged sequences, whose origin is discussed. Conclusions This analysis uncovers the importance of this small-sized genome diversity, which we expect to be present in a wide range of bacteria, and possibly also in many eukaryotic genomes.
Published: 2010
Full Text: View/download PDF

9. Identification of Amazonian trees with DNA barcodes

Author: Christopher Baraloto, Jérôme Chave, Julien Engel, Christophe Thébaud, Scott A. Mori, Mailyn Gonzalez, Aurélien Roger, Bernard Riera, Pascal Petronelli, Evolution et Diversité Biologique (EDB), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Ecologie des forêts de Guyane (ECOFOG), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université des Antilles et de la Guyane (UAG)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), New York Botanical Garden, New York Botanical Garden (NYBG), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genetic Markers, 0106 biological sciences, Ecology/Community Ecology and Biodiversity, DNA, Plant, [SDV]Life Sciences [q-bio], Biodiversity, lcsh:Medicine, Sciences du Vivant, Biology, 010603 evolutionary biology, 01 natural sciences, DNA barcoding, DNA sequencing, Trees, Plant identification, 03 medical and health sciences, Ecology/Conservation and Restoration Ecology, Ecology/Evolutionary Ecology, Cluster Analysis, lcsh:Science, Clade, Phylogeny, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Electronic Data Processing, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Models, Statistical, Multidisciplinary, Ecology, lcsh:R, Life Sciences, Sequence Analysis, DNA, SDV:GEN, 15. Life on land, Plant taxonomy, French Guiana, Taxon, lcsh:Q, Identification (biology), Seasons, Research Article
Abstract: Background Large-scale plant diversity inventories are critical to develop informed conservation strategies. However, the workload required for classic taxonomic surveys remains high and is particularly problematic for megadiverse tropical forests. Methodology/Principal Findings Based on a comprehensive census of all trees in two hectares of a tropical forest in French Guiana, we examined whether plant DNA barcoding could contribute to increasing the quality and the pace of tropical plant biodiversity surveys. Of the eight plant DNA markers we tested (rbcLa, rpoC1, rpoB, matK, ycf5, trnL, psbA-trnH, ITS), matK and ITS had a low rate of sequencing success. More critically, none of the plastid markers achieved a rate of correct plant identification greater than 70%, either alone or combined. The performance of all barcoding markers was noticeably low in few species-rich clades, such as the Laureae, and the Sapotaceae. A field test of the approach enabled us to detect 130 molecular operational taxonomic units in a sample of 252 juvenile trees. Including molecular markers increased the identification rate of juveniles from 72% (morphology alone) to 96% (morphology and molecular) of the individuals assigned to a known tree taxon. Conclusion/Significance We conclude that while DNA barcoding is an invaluable tool for detecting errors in identifications and for identifying plants at juvenile stages, its limited ability to identify collections will constrain the practical implementation of DNA-based tropical plant biodiversity programs.
Published: 2009
Full Text: View/download PDF

10. Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays

Author: Elodie Manié, Emmanuel Barillot, Marc-Henri Stern, Tatiana Popova, Dominique Stoppa-Lyonnet, Guillem Rigaill, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Biologie des Tumeurs, INSTITUT CURIE, Mathématiques et Informatique Appliquées ( MIA-Paris ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Département de recherche translationnelle, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, This work is part of the 'Cancéropôle Ile-de-France-Région Ile-de-France-Hereditary Breast Cancer' program coordinated by DSL and MHS. This work also was supported by the INSERM, the Institut Curie, and its Translational Research Department. TP is supported by a grant from the Cancéropôle Ile-de-France-Région Ile-de-France. GR is supported by a grant from the Institut National du Cancer (INCa)., Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie, Mathématiques et Informatique Appliquées (MIA-Paris), AgroParisTech-Institut National de la Recherche Agronomique (INRA), MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Département de Recherche Translationnelle, Mines Paris - PSL (École nationale supérieure des mines de Paris), and BMC, Ed.
Subjects: Method, Loss of Heterozygosity, MESH : Models, Genetic, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, Allelic Imbalance, MESH : Breast Neoplasms, Genome, Loss of heterozygosity, MESH: Genotype, Automation, MESH: Ploidies, 0302 clinical medicine, Models, MESH: Automation, Genotype, MESH: Models, Genetic, MESH : Karyotyping, Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genomics, Homozygote, MESH : Polymorphism, Single Nucleotide, Single Nucleotide, Genomics, MESH: Gene Expression Regulation, Neoplastic, SDV:GEN, Gene Expression Regulation, Neoplastic, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, MESH : Ploidies, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Homozygote, MESH : Gene Expression Regulation, Neoplastic, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Homozygote, Genetic, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], SNP, Humans, MESH: Genome, Polymorphism, MESH : Allelic Imbalance, 030304 developmental biology, MESH: Loss of Heterozygosity, Neoplastic, [SDV.GEN]Life Sciences [q-bio]/Genetics, Ploidies, MESH: Humans, Models, Genetic, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Genomics, MESH : Humans, MESH: Allelic Imbalance, Gene Expression Regulation, Karyotyping, SDV:BBM:GTP, Human genetics, MESH : Automation, Gene expression profiling, MESH: Karyotyping, MESH : Genome, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Breast Neoplasms, MESH : Loss of Heterozygosity
Abstract: GAP, a method for analyzing complex cancer genome profiles from SNP arrays, performs well even with poor quality data and rearranged genomes, We describe a method for automatic detection of absolute segmental copy numbers and genotype status in complex cancer genome profiles measured with single-nucleotide polymorphism (SNP) arrays. The method is based on pattern recognition of segmented and smoothed copy number and allelic imbalance profiles. Assignments were verified by DNA indexes of primary tumors and karyotypes of cell lines. The method performs well even for poor-quality data, low tumor content, and highly rearranged tumor genomes.
Published: 2009
Full Text: View/download PDF

11. Cell-to-cell stochastic variation in gene expression is a complex genetic trait

Author: Hélène Bottin, Christelle Damon, Juliet Ansel, Muniyandi Nagarajan, Camilo Rodriguez-Beltran, Steffen Fehrmann, Gaël Yvert, Jean Marie François, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Quantitative trait locus, Cancer Research, Transcription, Genetic, lcsh:QH426-470, Quantitative Trait Loci, Genomics, Locus (genetics), Saccharomyces cerevisiae, Biology, Genetics and Genomics/Complex Traits, Stochasticity, Genetics, Incomplete penetrance, Gene expression, Yeast, Transcriptional elongation, 03 medical and health sciences, 0302 clinical medicine, Gene mapping, Genetic variation, Uracil, Molecular Biology, Gene, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, DNA Primers, 0303 health sciences, Stochastic Processes, [SDV.GEN]Life Sciences [q-bio]/Genetics, Base Sequence, Models, Genetic, Molecular Biology/Transcription Elongation, Robustness (evolution), Genetic Variation, RNA, Fungal, Genetics and Genomics/Gene Expression, SDV:GEN, Genetics and Genomics/Bioinformatics, Genetics and Genomics/Microbial Evolution and Genomics, Genetic architecture, lcsh:Genetics, Phenotype, Genome, Fungal, 030217 neurology & neurosurgery, Research Article
Abstract: The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or ‘noise’). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits., Author Summary Although most inter-individual phenotypic variabilities are largely attributable to DNA differences, a wealth of examples illustrate how a single biological system can vary stochastically over time and between individuals. Identical twins are not identical, and similarly, clonal microbial cells differ in many aspects even when grown simultaneously in a common environment. Using yeast as a model system, we show that a population of isogenic cells all carrying genotype A showed higher cell-to-cell heterogeneity in gene expression than a population of isogenic cells of genotype B. We considered this level of intra-clonal heterogeneity as a quantitative trait and performed genetic linkage (on AxB) to search for regulators of it. This led to the demonstration that transcriptional elongation impairment increases stochastic variation in gene expression in vivo. Our results show that the two levels of inter-individual diversity, genetic and stochastic, are connected by a complex control of the former on the latter. We invite the community to revisit the interpretation of incomplete penetrance, which defines cases where a mutation does not cause the associated phenotype in all its carriers. We propose that, in the case of cancer or other diseases triggered by single cells, such mutations might increase stochastic molecular fluctuations and thereby the fraction of deviant cellular phenotypes in a human body.
Published: 2008
Full Text: View/download PDF

12. Architecture of Burkholderia cepacia complex σ70 gene family: evidence of alternative primary and clade-specific factors, and genomic instability

Author: Benoit Cournoyer, Paulina Estrada-de los Santos, Arnault Graindorge, Aymeric Menard, Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL)
Subjects: Burkholderia cenocepacia, lcsh:QH426-470, lcsh:Biotechnology, Biodiversité et Ecologie, Sigma Factor, Burkholderia cepacia, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Genomic Instability, Biodiversity and Ecology, Evolution, Molecular, 03 medical and health sciences, Species Specificity, Sigma factor, lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene duplication, Genetics, Gene family, Gene, Phylogeny, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, biology, 030306 microbiology, SDV:MP:BAC, fungi, SDV:GEN, DNA-Directed RNA Polymerases, SDV:BBM:GTP, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Burkholderia cepacia complex, lcsh:Genetics, Burkholderia, Genes, Bacterial, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, rpoS, Biotechnology, Research Article
Abstract: Background The Burkholderia cepacia complex (Bcc) groups bacterial species with beneficial properties that can improve crop yields or remediate polluted sites but can also lead to dramatic human clinical outcomes among cystic fibrosis (CF) or immuno-compromised individuals. Genome-wide regulatory processes of gene expression could explain parts of this bacterial duality. Transcriptional σ70 factors are components of these processes. They allow the reversible binding of the DNA-dependent RNA polymerase to form the holoenzyme that will lead to mRNA synthesis from a DNA promoter region. Bcc genome-wide analyses were performed to investigate the major evolutionary trends taking place in the σ70 family of these bacteria. Results Twenty σ70 paralogous genes were detected in the Burkholderia cenocepacia strain J2315 (Bcen-J2315) genome, of which 14 were of the ECF (extracytoplasmic function) group. Non-ECF paralogs were related to primary (rpoD), alternative primary, stationary phase (rpoS), flagellin biosynthesis (fliA), and heat shock (rpoH) factors. The number of σ70 genetic determinants among this genome was of 2,86 per Mb. This number is lower than the one of Pseudomonas aeruginosa, a species found in similar habitats including CF lungs. These two bacterial groups showed strikingly different σ70 family architectures, with only three ECF paralogs in common (fecI-like, pvdS and algU). Bcen-J2315 σ70 paralogs showed clade-specific distributions. Some paralogs appeared limited to the ET12 epidemic clone (ecfA2), particular Bcc species (sigI), the Burkholderia genus (ecfJ, ecfF, and sigJ), certain proteobacterial groups (ecfA1, ecfC, ecfD, ecfE, ecfG, ecfL, ecfM and rpoS), or were broadly distributed in the eubacteria (ecfI, ecfK, ecfH, ecfB, and rpoD-, rpoH-, fliA-like genes). Genomic instability of this gene family was driven by chromosomal inversion (ecfA2), recent duplication events (ecfA and RpoD), localized (ecfG) and large scale deletions (sigI, sigJ, ecfC, ecfH, and ecfK), and a phage integration event (ecfE). Conclusion The Bcc σ70 gene family was found to be under strong selective pressures that could lead to acquisition/deletion, and duplication events modifying its architecture. Comparative analysis of Bcc and Pseudomonas aeruginosa σ70 gene families revealed distinct evolutionary strategies, with the Bcc having selected several alternative primary factors, something not recorded among P. aeruginosa and only previously reported to occur among the actinobacteria.
Published: 2007
Full Text: View/download PDF

13. A two-step multiple-marker strategy for genome-wide association studies

Author: Guedj, Mickaël, Demenais, Florence, and Aschard, Hugues
Subjects: SDV:GEN
Abstract: Genome-wide association studies raise study-design and analytical issues that are still being debated. Among them, stands the issue of reducing the number of markers to be genotyped without loss of efficiency in identifying trait loci, which can reduce the cost of studies and minimize the multiple testing problem. With this aim, we proposed a two-step strategy based on two analytical methods suited to examine sets of markers rather than single markers: the local score, which screens the genome to select candidate regions in Step 1, and FBAT-LC, a multiple-marker family-based association test used to obtain significance levels of regions at step 2. The performance of this strategy was evaluated on all replicates of Genetic Analysis Workshop 15 Problem 3 simulated data, using the answers to that problem. Overall, seven of the nine generated trait loci were detected in at least 87% of the replicates using a framework designed to handle either association with the disease or association with the severity of disease. This multiple-marker strategy was compared to the single-marker approach. By considering regions instead of single markers, this strategy minimizes the multiple testing problem and the number of false-positive results.
Published: 2007

14. Genetic complexity and quantitative trait loci mapping of yeast morphological traits

Author: Gaël Yvert, Yoshikazu Ohya, Satoru Nogami, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo (UTokyo), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Cancer Research, Quantitative genetics, 0302 clinical medicine, Genetics (clinical), Genetics, 0303 health sciences, Cellular morphology, Chromosome Mapping, SDV:GEN, GTP-Binding Protein alpha Subunits, Functional genomics, Quantitative Trait Locus, Research Article, Saccharomyces cerevisiae Proteins, lcsh:QH426-470, Quantitative Trait Loci, Saccharomyces cerevisiae, Biology, Quantitative trait locus, Models, Biological, Polymorphism, Single Nucleotide, Microbiology, Transgressive segregation, 03 medical and health sciences, Saccharomyces, Quantitative Trait, Heritable, Gene mapping, Genetic variation, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Cell Size, Genetic diversity, [SDV.GEN]Life Sciences [q-bio]/Genetics, Complex Traits, Yeast, transcriptome, Genetic Variation, Computational Biology, Genetics and Genomics, Genetic architecture, lcsh:Genetics, Gene Expression Regulation, Evolutionary biology, Epistasis, GTP-Binding Protein alpha Subunits, Gq-G11, 030217 neurology & neurosurgery, Gene Deletion, Mathematics
Abstract: Functional genomics relies on two essential parameters: the sensitivity of phenotypic measures and the power to detect genomic perturbations that cause phenotypic variations. In model organisms, two types of perturbations are widely used. Artificial mutations can be introduced in virtually any gene and allow the systematic analysis of gene function via mutants fitness. Alternatively, natural genetic variations can be associated to particular phenotypes via genetic mapping. However, the access to genome manipulation and breeding provided by model organisms is sometimes counterbalanced by phenotyping limitations. Here we investigated the natural genetic diversity of Saccharomyces cerevisiae cellular morphology using a very sensitive high-throughput imaging platform. We quantified 501 morphological parameters in over 50,000 yeast cells from a cross between two wild-type divergent backgrounds. Extensive morphological differences were found between these backgrounds. The genetic architecture of the traits was complex, with evidence of both epistasis and transgressive segregation. We mapped quantitative trait loci (QTL) for 67 traits and discovered 364 correlations between traits segregation and inheritance of gene expression levels. We validated one QTL by the replacement of a single base in the genome. This study illustrates the natural diversity and complexity of cellular traits among natural yeast strains and provides an ideal framework for a genetical genomics dissection of multiple traits. Our results did not overlap with results previously obtained from systematic deletion strains, showing that both approaches are necessary for the functional exploration of genomes., Author Summary A familiar face or a dog breed is easily recognized because morphology of individuals differs according to their genetic backgrounds. For single-cell organisms, morphology reduces to the shape and size of cellular features. Microbiologists noticed that the shape of S. cerevisiae cells (baker's yeast) differs from one strain to another, but these differences were usually described qualitatively. We used a high-throughput imaging platform to study the morphology of yeast cells when they divide. Cells were stained with three fluorescent dyes so that their periphery, their DNA, and their actin could be recognized, and their images were analysed by a specialized software program. Numerous morphological differences were found between two distant strains of S. cerevisiae. By crossing these two strains, we performed quantitative genetics: several loci controlling morphological variations were found on the genome, and correlations were made between gene expression and morphology changes. Using bioinformatics, we showed that the results obtained do not overlap with previous results obtained from yeast cells in which specific genes are deleted. The study, therefore, illustrates how mutagenesis and the use of natural genetic variations provide complementary knowledge.
Published: 2006
Full Text: View/download PDF

15. Analysis of sequence variability in the CART gene in relation to obesity in a Caucasian population

Author: Guérardel, Audrey, Barat-Houari, Mouna, Vasseur, Francis, Dina, Christian, Vatin, Vincent, Clément, Karine, Eberlé, Delphine, Vasseur-Delannoy, Valérie, Bell, Christopher, Galan, Pilar, Hercberg, Serge, Helbecque, Nicole, Potoczna, Natascha, Horber, Fritz, Boutin, Philippe, Froguel, Philippe, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Déterminants Biologiques et Comportementaux des Obésités, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-EA3502, Genome Centre, Imperial College London-Hammersmith campus, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Dr. Horber Adipositas Stiftung, This research was supported in part by Pasteur Institute Lille and Region Nord-Pas de Calais with regards Audrey Guérardel and in part by the European Community Project NUGENOB (QLRTCT- 2000-00618, http://www.nugenob.com). The recruitment of French morbidly obese subjects was supported by the Direction de la Recherche Clinique/Assistance Publique-Hopitaux de Paris, the Programme Hospitalier de Recherche Clinique (AOM 96088)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Maylin, Françoise, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu-EA3502, and Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: lcsh:QH426-470, Genotype, European Continental Ancestry Group, Nerve Tissue Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Base Sequence, Research Support, MESH: Research Support, Non-U.S. Gov't, Polymorphism, Single Nucleotide, White People, MESH: Genotype, Genetic, Risk Factors, MESH: Risk Factors, MESH: Polymorphism, Genetic, Food and Nutrition, Humans, MESH: Obesity, Obesity, MESH: Nerve Tissue Proteins, Polymorphism, Non-U.S. Gov't, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, MESH: Humans, Base Sequence, MESH: Polymorphism, Single Nucleotide, SDV:GEN, Case-Control Studies, Single Nucleotide, MESH: European Continental Ancestry Group, MESH: Case-Control Studies, lcsh:Genetics, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Alimentation et Nutrition, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Research Article
Abstract: Background Cocaine and amphetamine regulated transcript (CART) is an anorectic neuropeptide located principally in hypothalamus. CART has been shown to be involved in control of feeding behavior, but a direct relationship with obesity has not been established. The aim of this study was to evaluate the effect of polymorphisms within the CART gene with regards to a possible association with obesity in a Caucasian population. Results Screening of the entire gene as well as a 3.7 kb region of 5' upstream sequence revealed 31 SNPs and 3 rare variants ; 14 of which were subsequently genotyped in 292 French morbidly obese subjects and 368 controls. Haplotype analysis suggested an association with obesity which was found to be mainly due to SNP-3608T>C (rs7379701) (p = 0.009). Genotyping additional cases and controls also of European Caucasian origin supported further this possible association between the CART SNP -3608T>C T allele and obesity (global p-value = 0.0005). Functional studies also suggested that the SNP -3608T>C could modulate nuclear protein binding. Conclusion CART SNP -3608T>C may possibly contribute to the genetic risk for obesity in the Caucasian population. However confirmation of the importance of the role of the CART gene in energy homeostasis and obesity will require investigation and replication in further populations.
Published: 2005
Full Text: View/download PDF

16. Genetic Evidence for a Link Between Glycolysis and DNA Replication

Author: Laurent Jannière, Danielle Canceill, Catherine Suski, Sophie Kanga, Bérengère Dalmais, Roxane Lestini, Anne-Françoise Monnier, Jérôme Chapuis, Alexander Bolotin, Marina Titok, Emmanuelle Le Chatelier, S. Dusko Ehrlich, 1Génétique Microbienne, INRA, Domaine de Vilvert, 78352 Jouy en Josas Cedex, Institut National de la Recherche Agronomique (INRA), Régulation de l'expression génétique chez les microorganismes (REGCM), Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), laboratoire de Virologie Immunologie Moléculaire, INRA, Jouy, and Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892))
Subjects: DNA Replication, dnaE, Science, Biology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, SDV:BBM, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Viability assay, Gene, Molecular Biology/DNA Replication, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Mutation, Multidisciplinary, DNA synthesis, 030306 microbiology, Microbiology and Parasitology, DNA replication, SDV:GEN, Microbiologie et Parasitologie, Genetics and Genomics/Chromosome Biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Biochemistry, Genes, Bacterial, Medicine, Microbiology/Microbial Physiology and Metabolism, Primase, Glycolysis, DNA, Research Article, Bacillus subtilis
Abstract: BackgroundA challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions.Methodology/principal findingsWe report here a tight link between glycolysis and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of glycolysis. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses.Conclusions/significanceOur findings provide the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous.
Published: 2007
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

16 results on '"SDV:GEN"'

1. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments

2. The Past, Present, and Future of Immune Repertoire Biology - The Rise of Next-Generation Repertoire Analysis

3. Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

4. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut

5. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

6. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers

7. Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers

8. Small variable segments constitute a major type of diversity of bacterial genomes at the species level

9. Identification of Amazonian trees with DNA barcodes

10. Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays

11. Cell-to-cell stochastic variation in gene expression is a complex genetic trait

12. Architecture of Burkholderia cepacia complex σ70 gene family: evidence of alternative primary and clade-specific factors, and genomic instability

13. A two-step multiple-marker strategy for genome-wide association studies

14. Genetic complexity and quantitative trait loci mapping of yeast morphological traits

15. Analysis of sequence variability in the CART gene in relation to obesity in a Caucasian population

16. Genetic Evidence for a Link Between Glycolysis and DNA Replication

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

16 results on '"SDV:GEN"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources