Search

Your search keyword '"SDV:GEN"' showing total 7 results
Start Over Descriptor "SDV:GEN" Topic medicine
7 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. 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

3. 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

4. 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

5. 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

6. 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

7. 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