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1. Functionally conserved enhancers with divergent sequences in distant vertebrates

Author: Boffelli, Dario [Children's Hospital Oakland Research Institute, Oakland, CA (United States)]
Published: 2015
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2. Genetic susceptibilities in the association between maternal exposure to tobacco smoke and the risk of nonsyndromic oral cleft

Author: Agnès Nelva, Christine Francannet, Sylvaine Cordier, Elisabeth Robert-Gnansia, Claire Perret, Christine Herman, Marie-Paule Vazquez, David M. Iovannisci, Michel Bahuau, Cécile Chevrier, Edward J. Lammer, Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Children's Hospital Oakland Research, Registre des Malformations Rhône-Alpes, REMERA, Centre d'Etude des Malformations Congénitales (CEMC), Centre d'Etude des Malformations Congénitales, Unité de Génétique Médicale, Hôtel-Dieu-CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Children's Hospital Oakland Research Institute, hildren's Hospital Oakland Research Institute, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de stomatologie et chirurgie maxillo-faciale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Forgeron, Christine
Subjects: Male, Passive smoking, Physiology, MESH: Logistic Models, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Tobacco smoke, MESH: Genotype, MESH: Pregnancy, Pregnancy, Risk Factors, MESH: Risk Factors, Smoke, Medicine, MESH: Maternal Exposure, MESH: Tobacco, Genetics (clinical), Glutathione Transferase, Genetics, 0303 health sciences, education.field_of_study, Smoking, 030305 genetics & heredity, MESH: Genetic Predisposition to Disease, MESH: Smoke, MESH: Case-Control Studies, MESH: Infant, 3. Good health, Cleft Palate, Maternal Exposure, Female, France, MESH: Pregnancy Trimester, First, MESH: Smoking, Genotype, Cleft Lip, Population, Genetic determinism, 03 medical and health sciences, Tobacco, MESH: Polymorphism, Genetic, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allele, Risk factor, education, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, MESH: Glutathione Transferase, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, MESH: Humans, business.industry, MESH: Cleft Lip, Infant, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, medicine.disease, MESH: Male, MESH: France, Pregnancy Trimester, First, Logistic Models, MESH: Cleft Palate, Case-Control Studies, Relative risk, business, MESH: Female
Abstract: International audience; Maternal tobacco consumption is considered as a risk factor for nonsyndromic oral clefts. However, this risk is moderate and may be modulated by genetic susceptibilities, including variants of the TGFA, TGFB3 and MSX1 developmental genes and polymorphisms of genes of the CYP (1A1, 2E1) and GST (M1, T1) families involved in metabolic pathways of tobacco smoke compounds. This French case-control study (1998-2001; 240 nonsyndromic cases, 236 controls) included a case-parent design (175 triad-families) that made it possible to distinguish the direct effect of the child's genotype and maternally mediated effects. Maternal smoking during the first trimester of pregnancy was not associated with the oral cleft risk in this population, but we observed statistically significant increased risks associated with maternal exposure to environmental tobacco smoke (ETS). No variant of any of the three developmental genes was significantly associated with oral cleft. The fetal CYP1A1*2C variant allele was associated with a statistically significant decreased risk, compared with the homozygous wild-type: relative risk = 0.48, 95% confidence interval: 0.2, 1.0. Suggestive reduced risks were also observed for the maternal CYP1A1*2C allele and the fetal CYP2E1*5 allele. The GSTM1 and GSTT1 deletions appeared to play no role. Our findings suggest some interactions, with the strongest between ETS and CYP1A1 or MSX1 and between maternal smoking and CYP2E1. We did not confirm the maternal smoking-infant GSTT1 null interaction previously reported by other investigators.
Published: 2008

3. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel

Author: Mat J.A.P. Daemen, Lale Tokgozoglu, Luis Masana, Brian A. Ference, Alberico L. Catapano, Ronald M. Krauss, Frederick J. Raal, Ulrich Laufs, Heribert Schunkert, Jan Borén, Chris J. Packard, Gerard Pasterkamp, Ulf Landmesser, Børge G. Nordestgaard, Jay D. Horton, Eric Bruckert, Olov Wiklund, Christoph J. Binder, Marja-Riitta Taskinen, Bart van de Sluis, Kausik K. Ray, Sergio Fazio, Robert A. Hegele, Ian D. Graham, M. John Chapman, Stephen J. Nicholls, Gerald F. Watts, Linda L. Demer, Henry N. Ginsberg, Jacob F. Bentzon, Gestionnaire, Hal Sorbonne Université, Sahlgrenska Academy at University of Gothenburg [Göteborg], Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], 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), Children's Hospital Oakland Research Institute (CHORI), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Glasgow, Aarhus University [Aarhus], Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), Medizinische Universität Wien = Medical University of Vienna, Amsterdam UMC - Amsterdam University Medical Center, Schulich School of Medicine and Dentistry, University of Western Ontario (UWO), Monash University [Melbourne], Copenhagen University Hospital, The University of Western Australia (UWA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Oregon Health and Science University [Portland] (OHSU), University of Cambridge [UK] (CAM), University of Bristol [Bristol], Trinity College Dublin, University of Texas Southwestern Medical Center, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Universität Leipzig [Leipzig], Universitat Rovira i Virgili, University Medical Center [Utrecht], University of the Witwatersrand [Johannesburg] (WITS), Imperial College London, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Center for Cardiovascular Research (DZHK), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University Medical Center Groningen [Groningen] (UMCG), Hacettepe University = Hacettepe Üniversitesi, Università degli Studi di Milano = University of Milan (UNIMI), Columbia University [New York], European Atherosclerosis Society, Center for Liver, Digestive and Metabolic Diseases (CLDM), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], University of California [San Francisco] (UCSF), University of California, Amsterdam UMC, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Technische Universität München [München] (TUM), University of Helsinki, Università degli Studi di Milano [Milano] (UNIMI), HUS Heart and Lung Center, Clinicum, CAMM - Research Program for Clinical and Molecular Metabolism, Research Programs Unit, and Faculty of Medicine
Subjects: 0301 basic medicine, Heart disease, Statement (logic), SMOOTH-MUSCLE-CELLS, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Bioinformatics, MESH: Atherosclerosis, Coronary artery disease, 0302 clinical medicine, Low density, 1102 Cardiorespiratory Medicine and Haematology, ComputingMilieux_MISCELLANEOUS, Atherosclerotic cardiovascular disease, APOPTOTIC CELL ACCUMULATION, Pathophysiology, ddc, 3. Good health, [SDV] Life Sciences [q-bio], Cardiovascular Diseases, Current Opinion, CORONARY-ARTERY-DISEASE, Cardiology and Cardiovascular Medicine, Translational Medicine, MESH: Cholesterol, LDL, Consensus, MONOCYTE-DERIVED MACROPHAGES, education, HEART-DISEASE, LIPID-LOWERING THERAPY, Lipid-lowering therapy, 03 medical and health sciences, ESTER TRANSFER PROTEIN, HIGH-INTENSITY STATIN, medicine, Humans, CHOLESTEROL-FED RABBITS, MESH: Consensus, MESH: Humans, business.industry, MESH: Cardiovascular Diseases, 1103 Clinical Sciences, Cholesterol, LDL, medicine.disease, Atherosclerosis, 030104 developmental biology, Cardiovascular System & Hematology, 3121 General medicine, internal medicine and other clinical medicine, European atherosclerosis society, business, TRIGLYCERIDE-RICH LIPOPROTEINS
Published: 2020

4. Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest

Author: Derek J. Pappas, Jarek Meller, Pierre-Antoine Gourraud, Vanja Paunic, Antoine Lizee, Steven J. Mack, Jill A. Hollenbach, Damjan Vukcevic, Karl R. Beutner, Lue Ping Zhao, Jacek Biesiada, Xiuwen Zheng, Martin Maiers, Stephen Leslie, Allan Motyer, Kent D. Taylor, Center for Genetics [Oakland, CA, USA], Children's Hospital Oakland Research Institute, Department of Neurology [San Francisco, CA, USA], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Bioinformatics Research [Minneapolis, MN, USA] (National Marrow Donor Program), National Marrow Donor Program [Minneapolis], Centre for Systems Genomics [Melbourne, Australia] (Schools of Mathematics and Statistics, and BioSciences), University of Melbourne-Schools of Mathematics and Statistics, and BioSciences [Melbourne, Australia], Murdoch Children’s Research Institute [Melbourne, Australia], Department of Biomedical Informatics [Cincinnati, OH, USA], University of Cincinnati (UC)-Cincinnati Children's Hospital Medical Center, Los Angeles Biomedical Research Institute (LA BioMed), Department of Biostatistics [Seattle, WA, USA], University of Washington [Seattle], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Département de Santé Publique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), ONR grant N00014-08-1-1207 (KB, DP, PAG, JAH, AL, SJM, MM and VP), NIH grants U01AI067068 (JAH and SJM) and U19AI067152 (ARRA administrative supplement) (PAG) awarded by the NIAID, R01GM109030 (JAH, SJM and DJP) and P01GM099568 (XZ) awarded by the NIGMS, RO1NS076492 (PAG), RO1NS046297 (PAG) and R01NS049477 (PAG) awarded by the NINDS, NMSS grant RG 2899-D11 (PAG), the Australian National Health and Medical Research Council (NHMRC) Career Development Fellowship ID 1053756 (SL), and by the Victorian Life Sciences Computation Initiative (VLSCI) grant number VR0240 on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government, Australia (SL). Research at the Murdoch Childrens Research Institute was supported by the Victorian Government’s Operational Infrastructure Support Program. PAG is a recipient of the Race to Erase MS Junior Investigator Award and the European Federation for Immunogenetics Julia Bodmer Award., Le Bihan, Sylvie, University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: 0301 basic medicine, Linkage disequilibrium, Genotype, Genome-wide association study, Human leukocyte antigen, HLA-C Antigens, Biology, Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, HLA Antigens, Genetics, HLA-B Antigens, SNP, Humans, Pharmacology & Pharmacy, Imputation (statistics), Polymorphism, 1000 Genomes Project, HLA Complex, Alleles, Pharmacology, Genome, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, HLA-A Antigens, Genome, Human, Human Genome, Genetic Variation, Single Nucleotide, Pharmacology and Pharmaceutical Sciences, 030104 developmental biology, Haplotypes, Molecular Medicine, Generic health relevance, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Human, Genome-Wide Association Study, HLA-DRB1 Chains
Abstract: International audience; Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall
Published: 2018

5. Prevalence of sexual dimorphism in mammalian phenotypic traits

Author: Damian Smedley, Colin McKerlie, Xiang Gao, Henrik Westerberg, Simon Greenaway, Monica J. Justice, Hiroshi Masuya, Elissa J. Chesler, Robert E. Braun, Mary E. Dickinson, Shay Yaacoby, Stephen A. Murray, Karen L. Svenson, Jeremy Mason, Martin Hrabé de Angelis, Luis Santos, Tania Sorg, Christopher J. Lelliott, Sara Wells, Ann M. Flenniken, Ruth Heller, Ann-Marie Mallon, Lynette Bower, Karen P. Steel, Helen Parkinson, Judith E. Mank, Arthur L. Beaudet, Kevin C K Lloyd, Richard Mott, Yann Herault, Yoav Benjamini, Jacqueline K. White, Steve D.M. Brown, Shiying Guo, John R. Seavitt, Helmut Fuchs, Natalja Kurbatova, Anneliese O. Speak, Natasha A. Karp, Ramiro Ramirez-Solis, Terrence F. Meehan, David B. West, Shigeharu Wakana, The Wellcome Trust Sanger Institute [Cambridge], AstraZeneca [Cambridge, UK], European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Baylor College of Medicine (BCM), Baylor University, Tel Aviv University (TAU), University of California [Davis] (UC Davis), University of California (UC), The Jackson Laboratory [Bar Harbor] (JAX), MRC Harwell Institute [UK], Helmholtz Zentrum München = German Research Center for Environmental Health, Technische Universität München = Technical University of Munich (TUM), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), Nanjing University (NJU), 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), French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Institut Clinique de la Souris (ICS), The Hospital for sick children [Toronto] (SickKids), University College of London [London] (UCL), RIKEN BioResource Research Center [Tsukuba, Japan] (RIKEN BRC), Queen Mary University of London (QMUL), King‘s College London, Children's Hospital Oakland Research Institute (CHORI), International Mouse Phenotyping Consortium: Yuichi Obata, Tomohiro Suzuki, Masaru Tamura, Hideki Kaneda, Tamio Furuse, Kimio Kobayashi, Ikuo Miura, Ikuko Yamada, Nobuhiko Tanaka, Atsushi Yoshiki, Shinya Ayabe, David A Clary, Heather A Tolentino, Michael A Schuchbauer, Todd Tolentino, Joseph Anthony Aprile, Sheryl M Pedroia, Lois Kelsey, Igor Vukobradovic, Zorana Berberovic, Celeste Owen, Dawei Qu, Ruolin Guo, Susan Newbigging, Lily Morikawa, Napoleon Law, Xueyuan Shang, Patricia Feugas, Yanchun Wang, Mohammad Eskandarian, Yingchun Zhu, Lauryl M J Nutter, Patricia Penton, Valerie Laurin, Shannon Clarke, Qing Lan, Khondoker Sohel, David Miller, Greg Clark, Jane Hunter, Jorge Cabezas, Mohammed Bubshait, Tracy Carroll, Sandra Tondat, Suzanne MacMaster, Monica Pereira, Marina Gertsenstein, Ozge Danisment, Elsa Jacob, Amie Creighton, Gillian Sleep, James Clark, Lydia Teboul, Martin Fray, Adam Caulder, Jorik Loeffler, Gemma Codner, James Cleak, Sara Johnson, Zsombor Szoke-Kovacs, Adam Radage, Marina Maritati, Joffrey Mianne, Wendy Gardiner, Susan Allen, Heather Cater, Michelle Stewart, Piia Keskivali-Bond, Caroline Sinclair, Ellen Brown, Brendan Doe, Hannah Wardle-Jones, Evelyn Grau, Nicola Griggs, Mike Woods, Helen Kundi, Mark N D Griffiths, Christian Kipp, David G Melvin, Navis P S Raj, Simon A Holroyd, David J Gannon, Rafael Alcantara, Antonella Galli, Yvette E Hooks, Catherine L Tudor, Angela L Green, Fiona L Kussy, Elizabeth J Tuck, Emma J Siragher, Simon A Maguire, David T Lafont, Valerie E Vancollie, Selina A Pearson, Amy S Gates, Mark Sanderson, Carl Shannon, Lauren F E Anthony, Maksymilian T Sumowski, Robbie S B McLaren, Agnieszka Swiatkowska, Christopher M Isherwood, Emma L Cambridge, Heather M Wilson, Susana S Caetano, Cecilia Icoresi Mazzeo, Monika H Dabrowska, Charlotte Lillistone, Jeanne Estabel, Anna Karin B Maguire, Laura-Anne Roberson, Guillaume Pavlovic, Marie-Christine Birling, Wattenhofer-Donze Marie, Sylvie Jacquot, Abdel Ayadi, Dalila Ali-Hadji, Philippe Charles, Philippe André, Elise Le Marchand, Amal El Amri, Laurent Vasseur, Antonio Aguilar-Pimentel, Lore Becker, Irina Treise, Kristin Moreth, Tobias Stoeger, Oana V Amarie, Frauke Neff, Wolfgang Wurst, Raffi Bekeredjian, Markus Ollert, Thomas Klopstock, Julia Calzada-Wack, Susan Marschall, Robert Brommage, Ralph Steinkamp, Christoph Lengger, Manuela A Östereicher, Holger Maier, Claudia Stoeger, Stefanie Leuchtenberger, AliÖ Yildrim, Lillian Garrett, Sabine M Hölter, Annemarie Zimprich, Claudia Seisenberger, Antje Bürger, Jochen Graw, Oliver Eickelberg, Andreas Zimmer, Eckhard Wolf, Dirk H Busch, Martin Klingenspor, Carsten Schmidt-Weber, Valérie Gailus-Durner, Johannes Beckers, Birgit Rathkolb, Jan Rozman, univOAK, Archive ouverte, Mason, Jeremy [0000-0002-2796-5123], Chesler, Elissa J [0000-0002-5642-5062], Angelis, Martin Hrabe de [0000-0002-7898-2353], Herault, Yann [0000-0001-7049-6900], Lelliott, Christopher J [0000-0001-8087-4530], McKerlie, Colin [0000-0002-2232-0967], Wakana, Shigeharu [0000-0001-8532-0924], Yaacoby, Shay [0000-0002-2583-4170], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Genotype, Science, Mutant, General Physics and Astronomy, [SDV.GEN] Life Sciences [q-bio]/Genetics, Quantitative trait locus, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Mice, Quantitative Trait, Quantitative Trait, Heritable, Genetics, Animals, Modifier, Gene, Heritable, Mammals, Sex Characteristics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, Genes, Modifier, Body Weight, General Chemistry, Phenotypic trait, Phenotype, Sexual dimorphism, 030104 developmental biology, Genes, Evolutionary biology, Female, International Mouse Phenotyping Consortium, Sex characteristics
Abstract: The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans., Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.
Published: 2017

6. Odd chain fatty acids:new insights of the relationship between the gut microbiota, dietary intake, biosynthesis and glucose intolerance

Author: Kaija J. Autio, Kalervo Hiltunen, Kevin Seyssel, Stéphane Hazebrouck, Ronald M. Krauss, Mary Courtney Moore, Pin-Ho Pan, Keith Summerhill, Renata Stepankova, Zsuzsanna Ament, Shih-Yi Lin, James A. West, Evelyn de Schryver, Julian L. Griffin, Walter Vetter, Albert Koulman, Sally Chiu, Martine Laville, Benjamin Jenkins, Sarah King, Martin J. J. Ronis, Alan D. Cherrington, Elizabeth Stanley, Chun-Jung Chen, Maud Alligier, Paul P. Van Veldhoven, Guillaume Kraft, Medical Research Council Human Nutrition Research, University of Cambridge, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Oakland Research Institute, All Children’s Hospital, Department Pediatric, Tungs' Taichung Metroharbor Hospital, Center Geriatric and Gerontology, Division Endocrinology and Metabolic, Taichung Veterans General Hospital, Institute Food Chemistry, University of Hohenheim, Biocenter Oulu, Faculty Biochemistry and Molecular Medicine, University of Oulu, Laboratoire d'Etudes et de Recherches en Immunoanalyses (LERI), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), 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)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institute Microbiology, Laboratory of Gnotobiology, Czech Academy of Sciences [Prague] (ASCR), Department of Medical Research, School Medicine, Department Molecular Physiology and Biophysics, Vanderbilt University [Nashville], Laboratory Lipid Biochemistry and Protein Interaction LIPIT, Université Catholique de Louvain, NIHR BRC Core Metabolic aand Lipid Laboratory, Cambridge University Hospitals (CUH), Medical Research Council for core funding UD99999906, Cambridge Lipidomics Biomarker Research Initiative G0800783, MRC Human Nutrition Research, GACR GA15-09518S, Czech Science Foundation, GACR 16-06326S, USDA ( ACNC-USDA-CRIS) 6251-51000- 005-03S, Hospices Civils de Lyon, Programme Hospitalier de Recherche Clinique Interregional, Agence Nationale de la Recherche (Programme de Recherche en Nutrition Humaine and the Programme National de Recherche en Alimentation), Innovation Strategique Industrielle program of the Agence pour l' Innovation OSEO, Academy of Finland 138690, Sigrid Juselius Foundation and NordForsk under the Nordic Centres of Excellence Programme in Food, Nutrition and Health 070010, NIH R01-DK-18243, Flemish 'Fonds Wetenschappelijk Onderzoek' G.0721.10N, KU Leuven OT/14/100, Ministere de l' Enseignement Superieur et de la Recherche (France), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Czech Academy of Sciences [Prague] (CAS), Université Catholique de Louvain = Catholic University of Louvain (UCL), 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), West, James [0000-0002-1535-7737], Griffin, Julian [0000-0003-1336-7744], Koulman, Albert [0000-0001-9998-051X], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Gerontology, Dietary Sugars, [SDV]Life Sciences [q-bio], microbiote digestif, Gut flora, 0601 Biochemistry and Cell Biology, biosynthèse, Oral and gastrointestinal, Mice, Medicine, Lipid profiling, Animal study, glucose, 2. Zero hunger, Multidisciplinary, biology, acide gras, Dietary intake, Fatty Acids, 3. Good health, endocrine system, 0299 Other Physical Sciences, Library science, Human study, Research initiative, Article, 03 medical and health sciences, Glucose Intolerance, Animals, Humans, Metabolic and endocrine, Nutrition, Extramural, business.industry, Prevention, predictive markers, Glucose Tolerance Test, biology.organism_classification, Dietary Fats, Biosynthetic Pathways, Diet, Gastrointestinal Microbiome, Rats, stomatognathic diseases, 030104 developmental biology, Dietary Supplements, lipidomics, Fat supplementation, fatty acid, biosynthesis, business, Digestive Diseases, apport alimentaire, intolérance
Abstract: Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1−/− mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1−/− only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.
Published: 2017

7. Comparative Analysis of piggyBac, CRISPR/Cas9 and TALEN Mediated BAC Transgenesis in the Zygote for the Generation of Humanized SIRPA Rats

Author: Laurent Tesson, Vanessa Chenouard, Lucas Brusselle, Laure-Hélène Ouisse, Claire Usal, Nicolas Poirier, Ignacio Anegon, Séverine Ménoret, Bernard Vanhove, Séverine Remy, Chris J. Jung, Pieter J. de Jong, Center for Genetics [Oakland, CA, USA], Children's Hospital Oakland Research Institute, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Plateforme 'Production de protéines recombinantes' (P2R - INSERM UMS016/CNRS UMS3556/UN FED4203), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), OSE Immunotherapeutics [Nantes, France], The 'TEFOR' project. The IHUCesti project is also supported by Nantes Métropole and Région Pays de la Loire., ANR-11-INBS-0014,TEFOR,Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles(2011), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Le Bihan, Sylvie, Infrastructures - Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles - - TEFOR2011 - ANR-11-INBS-0014 - INBS - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, ANR: ANRII-INSB-0014, ANR: ANR-11-LABX-0016-01, and ANR: ANR-10-IBHU005
Subjects: 0301 basic medicine, Chromosomes, Artificial, Bacterial, Zygote, Transgene, Mice, Transgenic, Computational biology, Biology, Article, Germline, Genome engineering, Mice, 03 medical and health sciences, Animals, Humans, CRISPR, Transgenes, Receptors, Immunologic, Gene, Genetics, Transcription activator-like effector nuclease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Cas9, Antigens, Differentiation, Rats, Transgenesis, 030104 developmental biology, CRISPR-Cas Systems, Rats, Transgenic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BAC transgenic mammalian systems offer an important platform for recapitulating human gene expression and disease modeling. While the larger body mass, and greater genetic and physiologic similarity to humans render rats well suited for reproducing human immune diseases and evaluating therapeutic strategies, difficulties of generating BAC transgenic rats have hindered progress. Thus, an efficient method for BAC transgenesis in rats would be valuable. Immunodeficient mice carrying a human SIRPA transgene have previously been shown to support improved human cell hematopoiesis. Here, we have generated for the first time, human SIRPA BAC transgenic rats, for which the gene is faithfully expressed, functionally active, and germline transmissible. To do this, human SIRPA BAC was modified with elements to work in coordination with genome engineering technologies-piggyBac, CRISPR/Cas9 or TALEN. Our findings show that piggyBac transposition is a more efficient approach than the classical BAC transgenesis, resulting in complete BAC integration with predictable end sequences, thereby permitting precise assessment of the integration site. Neither CRISPR/Cas9 nor TALEN increased BAC transgenesis. Therefore, an efficient generation of human SIRPA transgenic rats using piggyBac opens opportunities for expansion of humanized transgenic rat models in the future to advance biomedical research and therapeutic applications.
Published: 2016

8. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Timo A. Lakka, Kathleen Stirrups, Jean Ferrières, Ying Wu, Gulum Kosova, Toby Johnson, Heather M. Stringham, Bruce M. Psaty, Bruna Gigante, Göran Hallmans, Cornelia M. van Duijn, Kae Woei Liang, Niclas Eriksson, N. William Rayner, Lynda M. Rose, Stavroula Kanoni, Xueling Sim, Evangelos Evangelou, Philippe Froguel, Michel Burnier, Andrew P. Morris, Olle Melander, Martin Farrall, Albert V. Smith, Brendan J. Keating, Thomas Illig, Johan Sundström, Dorret I. Boomsma, Kate Witkowska, Ellen M. Schmidt, Aki S. Havulinna, Ann-Kristin Petersen, Paul F. O'Reilly, Young Jin Kim, Kari Kuulasmaa, Tom Wilsgaard, John D. Eicher, Marcus E. Kleber, Francis S. Collins, Rona J. Strawbridge, Ronald M. Krauss, Fotios Drenos, Stuart K. Kim, Ken K. Ong, Pascal Bovet, Danish Saleheen, Jaspal S. Kooner, Karl-Heinz Herzig, Tien Yin Wong, Benjamin F. Voight, Stefania Bandinelli, Stéphane Lobbens, Colin A. McKenzie, Jing Hua Zhao, Terrence Forrester, Louise A. Donnelly, Alice Stanton, Jean Dallongeville, Kirill V. Tarasov, Narisu Narisu, Jürgen Gräßler, Luigi Ferrucci, Peter S. Sever, Paul Elliott, Tune H. Pers, Andrew J. Smith, Tomas Axelsson, Young Ah Shin, Nora Franceschini, James F. Wilson, Vilmundur Gudnason, Kati Kristiansson, Andrew A. Hicks, Kent D. Taylor, Genovefa Kolovou, Andrew D. Morris, André G. Uitterlinden, Serena Sanna, Xiuqing Guo, Honghuang Lin, Aravinda Chakravarti, Wayne Huey-Herng Sheu, Panos Deloukas, Linda S. Adair, Diana Kuh, Murielle Bochud, Eric Boerwinkle, Inger Njølstad, Meena Kumari, Norman Klopp, Leo-Pekka Lyytikäinen, Steven C. Hunt, Weihua Zhang, Tõnu Esko, Pierre Meneton, Markus Perola, Erik P A Van Iperen, Georg Ehret, Veikko Salomaa, Lars Lind, Zoltán Kutalik, Cristiano Fava, Caroline Hayward, Hugh S. Markus, Teresa Ferreira, Stefan R. Bornstein, Vasyl Pihur, Patricia B. Munroe, Anne U. Jackson, Eirini Marouli, Gabriele Müller, Damiano Baldassarre, Jacques E. Rossouw, Dan E. Arking, Maija Hassinen, Nicholas J. Wareham, Robert Roberts, Daniel I. Chasman, I. Shou Chang, Sylvain Sebert, Tove Fall, Roby Joehanes, Patrik K. E. Magnusson, John C. Chambers, Peter Vollenweider, Wen Jane Lee, Dmitry Shungin, Mathias Gorski, Christopher Newton-Cheh, Anders Franco-Cereceda, Ching-Yu Cheng, Yun Kyoung Kim, Ruth J. F. Loos, Lude Franke, Karen L. Mohlke, Yii-Der Ida Chen, Carlos Iribarren, Martina Müller-Nurasyid, Alexander Teumer, Andrew D. Johnson, Antonella Mulas, Ulf Gyllensten, Martin D. Tobin, George Dedoussis, Rainford J. Wilks, Joshua C. Bis, Beverley Balkau, Jie Yao, Frida Renström, Themistocles L. Assimes, Morris Brown, Inês Barroso, Hyun Min Kang, Loic Yengo, Mika Kähönen, Christopher J. Groves, Kirsti Kvaløy, Rainer Rauramaa, Heribert Schunkert, Satu Männistö, Marjo-Riitta Järvelin, Nancy L. Pedersen, Karl Gertow, Rick Jansen, Thomas Quertermous, Jarmo Virtamo, Lazaros Lataniotis, Serge Hercberg, Paul M. Ridker, Osorio Meirelles, Jostein Holmen, Phil Howard, G. Kees Hovingh, Jeanette Erdmann, Jong-Young Lee, Peter Schwarz, Ramaiah Nagaraja, Elizabeth Theusch, Wei Zhao, Sonia Shah, Chao A. Hsiung, Santhi K. Ganesh, Richard S. Cooper, John M. C. Connell, Jian'an Luan, Graciela E. Delgado, Eric Kim, Daniel Levy, Li Lin, Jerome I. Rotter, Andres Metspalu, Nabila Bouatia-Naji, Christopher J. O'Donnell, Roberto Elosua, Andrew Wong, Alanna C. Morrison, Juha Saltevo, Michael R. Barnes, Alan B. Weder, Kay-Tee Khaw, Leena Moilanen, Peter S. Chines, Claudia Langenberg, Marika Kaakinen, Asif Rasheed, Annette Peters, Angela Döring, Alena Stančáková, Richard A. Jensen, Jaana Lindström, Alison H. Goodall, Toshiko Tanaka, Loukianos S. Rallidis, Dabeeru C. Rao, Ann-Christine Syvänen, Alun Evans, Brenda W.J.H. Penninx, Sarah Edkins, Xiaohui Li, Neil Poulter, Jouko Saramies, Ulf de Faire, Walter Palmas, Jaakko Tuomilehto, Louise V. Wain, Cristina Menni, Stephen Bevan, Maria X. Sosa, Nanette R. Lee, Anuj Goel, Germaine C. Verwoert, Kjell Nikus, Helen R. Warren, May E. Montasser, Ren-Hua Chung, Francesco Gianfagna, Kristian Hveem, Rainer Rettig, Unnur Thorsteinsdottir, Lori L. Bonnycastle, Tim D. Spector, Paul W. Franks, Bamidele O. Tayo, Ilja M. Nolte, John Danesh, E. Shyong Tai, Mika Kivimäki, Devin Absher, Oddgeir L. Holmen, Per Eriksson, Pirjo Komulainen, Peter P. Pramstaller, Cameron D. Palmer, He Gao, Elena Tremoli, H.-Erich Wichmann, Myriam Fornage, Gyda Bjornsdottir, Afshin Parsa, Anders Hamsten, Terho Lehtimäki, Lasse Folkersen, Janine F. Felix, Anna F. Dominiczak, Hinco J. Gierman, Edward G. Lakatta, Alex S. F. Doney, Erik Ingelsson, Colin N. A. Palmer, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Vladan Mijatovic, Mark I. McCarthy, Joel N. Hirschhorn, Winfried März, Nilesh J. Samani, Stefan Enroth, Mark J. Caulfield, Gudmar Thorleifsson, Tsun-Po Yang, François Mach, Cristen J. Willer, Claudia P. Cabrera, Aline Wagner, Michael Boehnke, Elias Salfati, Sekar Kathiresan, Ramachandran S. Vasan, Franco Giulianini, Harm-Jan Westra, Harold Snieder, Mark O. Goodarzi, M. Arfan Ikram, Fred Paccaud, Johannes H. Smit, Anna-Liisa Hartikainen, Xiaofeng Zhu, Markku Laakso, Ahmad Vaez, Albert Hofman, Amy J. Swift, Maria Hughes, I. Te Lee, Aroon D. Hingorani, Matti Uusitupa, Oscar H. Franco, Kenneth Rice, Veronique Vitart, Ross M. Fraser, Jouke-Jan Hottenga, Kari Stefansson, Dhananjay Vaidya, Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Saw Swee Hock School of Public Health, National University of Singapore (NUS), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Michigan System, Department of Computational Medicine and Bioinformatics (DCM&B), Queen Mary University of London (QMUL), GlaxoSmithKline, Glaxo Smith Kline, deCODE genetics [Reykjavik], University of Cambridge [UK] (CAM), University of Dundee, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Karolinska University Hospital [Stockholm], Umea University Hospital, Lund University [Lund], Queen's University [Belfast] (QUB), National Institutes of Health, Department of Genomics of Common Disease, Imperial College London, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), National Institute of Health and Welfare, Institute for Molecular Medicine Finland (FIMM), University College London Hospitals (UCLH), University Hospital of Heidelberg, Harbor UCLA Medical Center [Torrance, Ca.], University of Tampere, University of Verona (UNIVR), Uppsala University Hospital, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Stanford University School of Medicine [CA, USA], Medical School University of Athens, Partenaires INRAE, Children's Hospital Oakland Research Institute, Boston Children's Hospital, Broad Institute of Harvard and MIT, University of Copenhagen = Københavns Universitet (KU), Statens Serum Institut [Copenhagen], Framingham Heart Dis Epidemiol Study, Department of Psychiatry, VU University Medical Center [Amsterdam], National Heart, Lung and Blood Institute, Osong Health Technology Administration Complex, University of Pennsylvania, Department of Genetics, University of North Carolina at Chapel Hill (UNC), Loyola University [Chicago], Centre Hospitalier Universitaire Vaudois (CHUV), Hudson Alpha Institute for Biotechnology, Erasmus University Rotterdam, Department of Medical Sciences, Uppsala University, Università degli Studi di Milano [Milano] (UNIMI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], University of Lincoln, University of Washington [Seattle], Amgen Inc., The University of Texas Health Science Center at Houston (UTHealth), VU University Amsterdam, University of Dresden Medical School, Université de Lausanne (UNIL), Healthcare NHS Trust, National Health Research Institutes, National University Health System [Singapore] (NUHS), Duke-NUS Medical School [Singapore], Singapore Eye Research Institute [Singapore] (SERI), National Human Genome Research Institute (NHGRI), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Radiology and nuclear medicine, EMGO - Mental health, Lin, Li, Mach, François, ProdInra, Migration, University of Oxford, Università degli studi di Verona = University of Verona (UNIVR), University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano = University of Milan (UNIMI), Vrije Universiteit Amsterdam [Amsterdam] (VU), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), EMGO+ - Lifestyle, Overweight and Diabetes, Biological Psychology, APH - Amsterdam Public Health, Epidemiology and Data Science, Graduate School, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Danesh, John [0000-0003-1158-6791], Khaw, Kay-Tee [0000-0002-8802-2903], Markus, Hugh [0000-0002-9794-5996], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Zhao, Jing Hua [0000-0003-4930-3582], Langenberg, Claudia [0000-0002-5017-7344], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium, Medical Microbiology & Infectious Diseases, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Clinical Genetics, Biochemistry, National Institute for Health Research, and Medical Research Council (MRC)
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), CHROMATIN, [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Blood Pressure, SUSCEPTIBILITY, Bioinformatics, Cardiovascular, Genome-wide association studies, Medical and Health Sciences, single nucleotide polymorphism, CHARGE-EchoGen consortium, GWAS, 2.1 Biological and endogenous factors, Aetiology, Cells, Cultured, African Continental Ancestry Group, Genetics & Heredity, Genetics, ddc:616, Kidney, Framingham Risk Score, Cultured, COMMON VARIANTS, 11 Medical And Health Sciences, Single Nucleotide, Biological Sciences, African Continental Ancestry Group/genetics, Asian Continental Ancestry Group/genetics, Blood Pressure/genetics, Genome-Wide Association Study, Humans, Hypertension/genetics, Hypertension/pathology, Microarray Analysis, Polymorphism, Single Nucleotide, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Hypertension/genetics/pathology, Hypertension, Medical genetics, Wellcome Trust Case Control Consortium, Life Sciences & Biomedicine, TRAITS, Biotechnology, Asian Continental Ancestry Group, medicine.medical_specialty, CHARGE-EchoGen Consortium, Cells, Black People, BIOLOGY, Single-nucleotide polymorphism, Biology, Blood pressure, hypertension, genetics, single nucleotide polymorphism, GWAS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Asian People, medicine, Polymorphism, GENOME-WIDE ASSOCIATION, CELL-TYPES, METAANALYSIS, Genetic association, Science & Technology, CHARGE-HF consortium, 06 Biological Sciences, Genetic architecture, 030104 developmental biology, Blood pressure, CHARGE-HF Consortium, ARTERIAL-HYPERTENSION, Developmental Biology
Abstract: To dissect the genetic architecture of blood pressure (BP) and assess how its elevation promotes downstream cardiovascular diseases, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry. Genotypes from an additional 140,886 individuals of European ancestry were used as validation for loci reaching genome-wide significance but without prior support in the literature. We identified 66 BP loci, of which 17 were novel and 15 harbored multiple distinct association signals, and which together explain up to 3.5% of BP variation. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in BP control through modulating blood vessel tone and fluid filtration across multiple tissues, not solely the kidney. Importantly, the 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent (South-Asian, East-Asian and African), confirming that these are ancestral physiological effects that arose prior to human migration out of Africa. The 66-SNP BP risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our data expand current knowledge of BP pathways, and also, highlight that BP regulation and its effects may occur in multiple organs and tissues beyond the classic renal system.
Published: 2016

9. Diagnosis and management of ophthalmological features in patients with mucopolysaccharidosis

Author: C. Gail Summers, Paul Harmatz, Jane Ashworth, Diego Ponzin, Maurizio Scarpa, Stefano Ferrari, Kristina Teär Fahnehjelm, The Veneto Eye Bank Foundation, Venice, Manchester Royal Eye Hospital, Manchester, St. Erik Eye Hospital, Karolinska University Hospital, Huddinge, Departments of Ophthalmology and Pediatrics, University of Minnesota, Minneapolis, MN, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Children's Hospital & Research Center Oakland, Oakland, CA, Children's Hospital Oakland Research Institute (CHORI), and Universita degli Studi di Padova
Subjects: Male, medicine.medical_specialty, Pediatrics, Eye Diseases, genetic structures, Mucopolysaccharidosis, Ocular Pathology, Ocular hypertension, Glaucoma, Disease, Severity of Illness Index, Imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, Corneal Opacity, 0302 clinical medicine, Severity of illness, Pathology, medicine, Humans, business.industry, Enzyme replacement therapy, Mucopolysaccharidoses, medicine.disease, eye diseases, Sensory Systems, 3. Good health, Surgery, Transplantation, Ophthalmology, Phenotype, 030221 ophthalmology & optometry, Female, Ocular Hypertension, Diagnostic tests/Investigation, Treatment Medical, sense organs, Child health (paediatrics), business, 030217 neurology & neurosurgery
Abstract: International audience; Ocular pathology is common in patients with mucopolysaccharidosis (MPS), an hereditary lysosomal storage disorder, where the eye as well as other tissues accumulate excessive amounts of glycosaminoglycans. Despite genetic and phenotypic heterogeneity within and between different types of MPS, the disease symptoms and clinical signs often manifest during the first six months of life with increasing head size, recurrent infections, umbilical hernia, growth retardation and skeletal problems. Typical ocular features include corneal clouding, ocular hypertension/glaucoma, retinal degeneration and optic nerve atrophy. Visual deterioration and sensitivity to light may substantially reduce the quality of life in MPS patients, particularly when left untreated. As an early intervention, haematopoietic stem cell transplantation and/or enzyme replacement therapy are likely to improve patients' symptoms and survival, as well as visual outcome. Thus, it is of utmost importance to ensure proper detection and accurate diagnosis of MPS at an early age. Fundamental herein is to increase awareness and knowledge among ophthalmologists of the ocular problems affecting MPS patients and to highlight potential diagnostic pitfalls and difficulties in patient care. This review provides insight into the prevalence and severity of ocular features in patients with MPS and gives guidance for early diagnosis and follow-up of MPS patients. MPS poses therapeutic challenges in ocular management, which places ophthalmologists next to paediatricians at the forefront of interventions to prevent long-term sequelae of this rare but serious disease.
Published: 2010

10. Evolutionary movement of centromeres in horse, donkey, and zebra

Author: Maria Francesca Piras, Doriana Misceo, Carmen Attolini, Lucia Carbone, Solomon G. Nergadze, Gérard Guérin, Elisa Magnani, Mariano Rocchi, Pieter J. de Jong, Livia Bertoni, Nicoletta Archidiacono, Bhanu P. Chowdhary, Elena Giulotto, Terje Raudsepp, Maria Francesca Cardone, Roberta Roberto, Department of Genetics and Microbiology, Università degli studi di Bari Aldo Moro (UNIBA), Università degli Studi di Pavia, Partenaires INRAE, Children's Hospital Oakland Research Institute, Department of Veterinary Anatomy and Public Health, Texas A&M University System, Unité de recherche Génétique Biochimique et Cytogénétique (LGBC), and Institut National de la Recherche Agronomique (INRA)
Subjects: Genetic Markers, Chromosomes, Artificial, Bacterial, Time Factors, Evolution, [SDV]Life Sciences [q-bio], Centromere, Population, Zoology, Horse, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, Molecular evolution, Donkey, Genetics, Animals, Horses, education, ComputingMilieux_MISCELLANEOUS, In Situ Hybridization, Fluorescence, 030304 developmental biology, 0303 health sciences, education.field_of_study, Genus Equus, biology, Chromosome, Karyotype, Equidae, Centromere repositioning, biology.organism_classification, Biological Evolution, Equus, Equus asinus, CENTROMERE REPOSITIONING, CENTROMERE, DONKEY, HORSE, EVOLUTION, 030217 neurology & neurosurgery
Abstract: Centromere repositioning (CR) is a recently discovered biological phenomenon consisting of the emergence of a new centromere along a chromosome and the inactivation of the old one. After a CR, the primary constriction and the centromeric function are localized in a new position while the order of physical markers on the chromosome remains unchanged. These events profoundly affect chromosomal architecture. Since horses, asses, and zebras, whose evolutionary divergence is relatively recent, show remarkable morphological similarity and capacity to interbreed despite their chromosomes differing considerably, we investigated the role of CR in the karyotype evolution of the genus Equus. Using appropriate panels of BAC clones in FISH experiments, we compared the centromere position and marker order arrangement among orthologous chromosomes of Burchelli’s zebra (Equus burchelli), donkey (Equus asinus), and horse (Equus caballus). Surprisingly, at least eight CRs took place during the evolution of this genus. Even more surprisingly, five cases of CR have occurred in the donkey after its divergence from zebra, that is, in a very short evolutionary time (approximately 1 million years).These findings suggest that in some species the CR phenomenon could have played an important role in karyotype shaping, with potential consequences on population dynamics and speciation. D 2005 Elsevier Inc. All rights reserved.
Published: 2006

11. Comparison between a Camera and a Four Quadrant Detector, in the Measurement of Red Blood Cell Deformability as a Function of Osmolality

Author: Finkelstein, Arie, Talbot, Hugues, Topsu, Suat, Cynober, Thérèse, Garçon, Loïc, Havkin, Gregor, Kuypers, Frans, ISYS (ISYS), ESIEE Paris, Laboratoire d'Informatique Gaspard-Monge (LIGM), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), Laboratoire d'Ingénierie des Systèmes de Versailles (LISV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire d'hématologie, Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cold Spring Harbor Laboratory, Children's Hospital Oakland Research Institute, Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), and Talbot, Hugues
Subjects: ektacytometry, [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, diffraction, Ektacytometer, red blood cell, [SPI.TRON] Engineering Sciences [physics]/Electronics, shear stress, [SPI.TRON]Engineering Sciences [physics]/Electronics, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, deformability, osmolality, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: 4 pages; International audience; The ability of red blood cells (RBC) to deform under vascular conditions is essential for circulation. RBC deformability, measured at different shear rates and osmolalities, provides a useful way to evaluate RBC function and is used to diagnose several hereditary blood disorders. In clinical practice, ektacytometry has been used as a routine automated technique for measuring RBC deformability under shear stress at known osmolalities. RBC suspension is exposed to laser light and the resulting diffraction pattern is recorded. The mean deformability of the cells is characterized by the diffraction pattern. Our study is the first to compare the correspondence between two methods that measure diffraction simultaneously, on the same apparatus. Additionally, while others conducted studies under varying shear we used varying osmolalities. A laser beam splitter produced two identical diffraction patterns, evaluated by synchronous data acquisition and analysis: One pattern was acquired by a digital camera and analyzed by image processing software. The other was analyzed using photodiode measurement at four fixed points and a microcontroller interface. Data analysis resulted in two deformability vs. osmolality curves. Comparing these curves shows excellent overlap in shape with a clear difference in amplitude. Since routine Manuscript received Jan 15, 2013; revised March 1, 2013. patient curves are always compared to a normal control curve, the amplitue difference is not significant. Our results indicate that either method may be used for clinically-usable interpretation of RBC deformability, but also that additional studies are required in order to compare repeatability for both methods, and to demonstrate that the two curves overlap for a variety of pathologies.
Published: 2013

12. The Transcription Factor Encyclopedia

Author: Yusuf, Dimas, Butland, Stefanie L., Swanson, Magdalena I., Bolotin, Eugene, Ticoll, Amy, Cheung, Warren A., Zhang, Xiao Yu Cindy, Dickman, Christopher T. D., Fulton, Debra L., Lim, Jonathan S., Schnabl, Jake M., Ramos, Oscar H. P., Vasseur-Cognet, Mireille, de Leeuw, Charles N., Simpson, Elizabeth M., Ryffel, Gerhart U., Lam, Eric W.-F., Kist, Ralf, Wilson, Miranda S. C., Marco-Ferreres, Raquel, Brosens, Jan J., Beccari, Leonardo L., Bovolenta, Paola, Benayoun, Bérénice A., Monteiro, Lara J, Schwenen, Helma D C, Grontved, Lars, Wederell, Elizabeth, Mandrup, Susanne, Veitia, Reiner A, Chakravarthy, Harini, Hoodless, Pamela A., Mancarelli, M Michela, Torbett, Bruce E, Banham, Alison H, Reddy, Sekhar P, Cullum, Rebecca L, Liedtke, Michaela, Tschan, Mario P, Vaz, Michelle, Rizzino, Angie, Zannini, Mariastella, Frietze, Seth, Farnham, Peggy J, Eijkelenboom, Astrid, Brown, Philip J, Laperrière, David, Leprince, Dominique, de Cristofaro, Tiziana, Prince, Kelly L, Putker, Marrit, del Peso, Luis, Camenisch, Gieri, Wenger, Roland H, Mikula, Michal, Rozendaal, Marieke, Mader, Sylvie, Ostrowski, Jerzy, Rhodes, Simon J, Van Rechem, Capucine, Boulay, Gaylor, Olechnowicz, Sam W Z, Breslin, Mary B, Lan, Michael S, Nanan, Kyster K, Wegner, Michael, Hou, Juan, Mullen, Rachel D, Colvin, Stephanie C, Noy, Peter John, Webb, Carol F, Witek, Matthew E, Ferrell, Scott, Daniel, Juliet M, Park, Jason, Waldman, Scott A, Peet, Daniel J, Taggart, Michael, Jayaraman, Padma-Sheela, Karrich, Julien J, Blom, Bianca, Vesuna, Farhad, O'Geen, Henriette, Sun, Yunfu, Gronostajski, Richard M, Woodcroft, Mark W, Hough, Margaret R, Chen, Edwin, Europe-Finner, G Nicholas, Karolczak-Bayatti, Magdalena, Bailey, Jarrod, Hankinson, Oliver, Raman, Venu, LeBrun, David P, Biswal, Shyam, Harvey, Christopher J, DeBruyne, Jason P, Hogenesch, John B, Hevner, Robert F, Héligon, Christophe, Luo, Xin M, Blank, Marissa Cathleen, Millen, Kathleen Joyce, Sharlin, David S, Forrest, Douglas, Dahlman-Wright, Karin, Zhao, Chunyan, Mishima, Yuriko, Sinha, Satrajit, Chakrabarti, Rumela, Portales-Casamar, Elodie, Sladek, Frances M, Bradley, Philip H, Wasserman, Wyeth W, Cindy Zhang, Xiao, Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Evaluation and Research Services, Fraser Health Authority, Children's Hospital Oakland, Oakland Research Institute, Computational Biology Program, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Department of Bioinformatics, Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Department of Biology, University of Western Ontario (UWO), Genetics Program, Department of Cell Biology and Neuroscience [Riverside] (CBNS), University of California [Riverside] (UC Riverside), University of California (UC)-University of California (UC), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut für Zellbiologie, Universität Duisburg-Essen [Essen]-Universitätsklinikum Essen, Department of Surgery and Cancer, Imperial College London-Division of Cancer, Centre for Oral Health Research, Newcastle University [Newcastle]-Medical School-School of Dental Sciences, Department of Development and Differentiation, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-CIBER de Enfermedades Raras (CIBERER), Division of Reproductive Health, University of Warwick [Coventry]-Warwick Medical School, University of Warwick [Coventry], Neurobiologia Molecular Celular y del desarrollo, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-Provincial Health Services Authority, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, Department of Molecular Experimental Medicine, The Scripps Research Institute [La Jolla, San Diego], Departments of Molecular and Experimental Medicine and Immunology and Microbial Sciences (MEM 131), Nuffield Department of Clinical Laboratory Sciences, University of Oxford- John Radcliffe Hospital [Oxford University Hospital]-Oxford NIHR Biomedical Research Centre, Department of Pediatrics, College of Medicine-Department of pediatrics-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Division of Hematology [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Medicine, University of Bern, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine, Institute of Experimental Endocrinology and Oncology (IEOS), Consiglio Nazionale delle Ricerche (CNR), University of Southern California (USC)-Norris Comprehensive Cancer Center, Department of Molecular Cancer Research, University Medical Center [Utrecht]-Utrecht University [Utrecht], University of Oxford- John Radcliffe Hospital [Oxford University Hospital]-Medical Sciences Division, Molecular Targeting in Breast Cancer research unit, Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Physiological Chemistry, Department of Biochemistry, Universidad Autónoma de Madrid (UAM)-School of Medicine, Institute of Physiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, Department of Oncological Genetics, Institute of Oncology-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC)-Medical Center of Postgraduate Education [Warsaw] (MCPE), Indiana University [Bloomington], Indiana University System-Indiana University System-School of Science, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston]-Cancer Center, University of Adelaide-School of Molecular and Biomedical Science, Department of Pediatrics and Biochemistry and Molecular Biology, Louisiana State University (LSU)-Research Institute for Children-Children's Hospital at New Orleans, Departments of Pediatrics and Genetics, Department of Pathology and Molecular Medicine, Queen's University [Kingston, Canada]-Queen's Cancer Research Institute, School of Medicine [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Institut fuer Biochemie-Emil-Fischer-Zentrum, Department of Molecular Biology and Biochemistry, University Indianapolis-Indiana University School of Medicine, Department of Immunity and Infection, School of Medical and Dental Sciences-University of Birmingham [Birmingham], Immunobiology and Cancer Program, Oklahoma Medical Research Foundation (OMRF), Radiation Oncology, Department of Pharmacology and Experimental Therapeutics-Jefferson University Hospitals, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), McMaster University [Hamilton, Ontario], School of Medicine, Johns Hopkins University (JHU), Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University-Jefferson Medical College, Discipline of Biochemistry, Institute of Cellular Medicine, Newcastle University [Newcastle]-Faculty of Medicine-Medical School, Department of Immunity and Immunology, Department of Cell Biology and Histology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Immunology Amsterdam, Division of Cancer Imaging Research, Johns Hopkins University (JHU)-School of Medicine-Department of Radiology, Genome Center [UC Davis], University of California [Davis] (UC Davis), School of Biological Sciences [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), Department of Biochemistry and Developmental Genomics Group, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY)-State University of New York (SUNY)-Center of Excellence in Bioinformatics and Life Sciences, Department of Molecular and Cellular Biology, University of Toronto-Sunnybrook Health Sciences Centre-Department of Laboratory Medicine and Pathobiology, Faculty of Medical Sciences, Newcastle University [Newcastle]-Medical School-Institute of Cellular Medicine, Department of Pathology and Laboratory Medicine, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Radiology and Oncology, Johns Hopkins University (JHU)-School of Medicine, Department of Environmental Health Sciences, Johns Hopkins University (JHU)-Johns Hopkins Bloomberg School of Public Health [Baltimore], Department of Pharmacology and Toxicology, Neuroscience Institute-Morehouse School of Medicine, Department of Pharmacology, University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Department of Neurological Surgery, University of Washington [Seattle]-Seattle Children's Research Institute, Faculty of Biology and Medicine, Université de Lausanne = University of Lausanne (UNIL)-Center for Integrated Genomics, Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University [Blacksburg]-Virginia-Maryland College of Veterinary Medicine, Department of Molecular Genetics and Cell Biology, University of Illinois [Chicago] (UIC), Center for Integrative Brain Research, University of Washington [Seattle], Clinical Endocrinology Branch, National Institutes of Health (NIH)-National Institute of Diabetes, Digestive, and Kidney Disorders, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], State University of New York (SUNY)-State University of New York (SUNY), BMC, Ed., Universität Duisburg-Essen = University of Duisburg-Essen [Essen]-Universitätsklinikum Essen, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), UAM. Departamento de Bioquímica, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia ( UBC ), Fred Hutchinson Cancer Research Center [Seattle] ( FHCRC ) -Public Health Sciences Division, Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia ( UBC ), University of Western Ontario ( UWO ), Department of Cell Biology and Neuroscience [Riverside] ( CBNS ), University of California [Riverside] ( UCR ), Service d'Ingénierie Moléculaire des Protéines ( SIMOPRO ), Département Médicaments et Technologies pour la Santé ( DMTS ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-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 ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CIBER de Enfermedades Raras (CIBERER)-Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Centro de Biologia Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Centro de Biologia Molecular Severo Ochoa (CBMSO)-CIBER de Enfermedades Raras (CIBERER), Service de Pathologies moléculaire et cellulaire, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), UNIVERSITY OF SOUTHERN DENMARK, BC Cancer Agency ( BCCRC ) -Provincial Health Services Authority, Scripps Research Institute, Departments of Molecular and Experimental Medicine and Immunology and Microbial Sciences ( MEM 131 ), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-Oxford NIHR Biomedical Research Centre, College of Medicine-Department of pediatrics-University of Illinois at Chicago ( UIC ), Department of Medicine/Hematology, Stanford University School of Medicine, Institute of Experimental Endocrinology and Oncology ( IEOS ), CNR - National Research Council, University of Southern California ( USC ) -Norris Comprehensive Cancer Center, Utrecht University [Utrecht]-University Medical Center Utrecht, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-Medical Sciences Division, Université de Montréal-Institute for Research in Immunology and Cancer, Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Lille, Droit et Santé, Utrecht University [Utrecht]-University Medical Centre Utrecht, Universidad Autonoma de Madrid ( UAM ) -School of Medicine, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Institute of Oncology-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC ) -Medical Center of Postgraduate Education [Warsaw] ( MCPE ), Indiana University [Bloomington]-School of Science, Harvard Medical School [Boston] ( HMS ) -Cancer Center-Massachusetts General Hospital, Louisiana State University Health Sciences Center-Research Institute for Children-Children's Hospital at New Orleans, Queen's University [Kingston]-Queen's Cancer Research Institute, Institut fuer Biochemie-Emil-Fischer-Zentrum-Friedrich-Alexander Universitaet Erlangen-Nuernberg, Indiana University School of Medicine-University Indianapolis, Oklahoma Medical Research Foundation, Department of Pharmacology and Experimental Therapeutics-Jefferson University Hospital, University of Oklahoma Health Sciences Center ( OUHSC ), Johns Hopkins University ( JHU ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ) -Center for Immunology Amsterdam, Johns Hopkins University ( JHU ) -School of Medicine-Department of Radiology, University of California at Davis, Division of Biological Sciences [San Diego], University of California [San Diego] ( UC San Diego ), State University of New York at Buffalo ( SUNY Buffalo ) -Center of Excellence in Bioinformatics and Life Sciences, University of California at Los Angeles [Los Angeles] ( UCLA ) -David Geffen School of Medicine, Johns Hopkins University ( JHU ) -School of Medicine, Johns Hopkins University ( JHU ) -Johns Hopkins Bloomberg School of Public Health, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Lausanne-Center for Integrated Genomics, Virginia Polytechnic Institute and State University [Blacksburg]-VA-MD Regional College of Veterinary Medicine, University of Illinois at Chicago ( UIC ), State University of New York at Buffalo ( SUNY Buffalo ) -University of Buffalo School of Medicine and Biomedical Sciences, University of California [Riverside] (UCR), University of California-University of California, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-CIBER de Enfermedades Raras (CIBERER), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Johns Hopkins University School of Medicine-The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore], Utrecht University [Utrecht]-University Medical Center [Utrecht], Universidad Autonoma de Madrid (UAM)-School of Medicine, Cancer Center-Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Emil-Fischer-Zentrum-Institut fuer Biochemie, School of Molecular and Biomedical Science-University of Adelaide, School of Medicine-Department of Radiology-Johns Hopkins University (JHU), University of California-University of California-David Geffen School of Medicine [Los Angeles], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), University of Pennsylvania [Philadelphia], Université de Lausanne (UNIL)-Center for Integrated Genomics, AII - Amsterdam institute for Infection and Immunity, and Cell Biology and Histology
Subjects: Encyclopedias as Topic, INFORMATION, WIKI, Transcription, Genetic, 05 Environmental Sciences, Medizin, [SDV.GEN] Life Sciences [q-bio]/Genetics, Automate Content, Web API, ANNOTATION, Mini review, Mice, 0302 clinical medicine, Portable Document Format, GENETICS & HEREDITY, Databases, Protein, Informática, 0303 health sciences, PROTEIN DATA-BANK, Application programming interface, BIOTECHNOLOGY & APPLIED MICROBIOLOGY, MENDELIAN-INHERITANCE, ddc:57, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, Application Programming Interface, Encyclopedia, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], The Internet, Transcription (software), Transcription, Life Sciences & Biomedicine, KNOWLEDGEBASE, Medicina, DATABASE, Bioinformatics, Biology, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Zellbiologie (Tumorforschung), World Wide Web, Access to Information, 03 medical and health sciences, Databases, Genetic, Protein Data Bank, ddc:570, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:61, Animals, Humans, ddc:610, MeSH Term, Transcription factor, 030304 developmental biology, Internet, 08 Information And Computing Sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, GENE-REGULATION, business.industry, Protein, Computational Biology, 06 Biological Sciences, Compendium, EVOLUTION, Rats, Evolutionary biology, UPDATE, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Software, Transcription Factors
Abstract: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.
Published: 2012

13. SECIS-binding protein 2, a key player in selenoprotein synthesis, is an intrinsically disordered protein

Author: Catherine Birck, Vincent Olieric, Philippe Dumas, Guillaume Bec, Akiko Takeuchi, A. D. Beniaminov, Alain Krol, Bruno Kieffer, Christine Allmang, Marc Vitorino, Giorgio Cavigiolio, Philippe Wolff, Elizabeth C. Theil, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Engelhardt Institute of Molecular Biology (ISTC), Russian Academy of Sciences [Moscow] (RAS), Children's Hospital Oakland Research Institute (CHORI), CHORI, Department of Nutritional Sciences and Toxicology [Berkeley] (NST ), University of California [Berkeley], University of California-University of California, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Peney, Maité, University of California [Berkeley] (UC Berkeley), and University of California (UC)-University of California (UC)
Subjects: Untranslated region, Protein Denaturation, Molecular Sequence Data, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Selenoproteins, Peptide sequence, SECIS element, 030304 developmental biology, Genetics, chemistry.chemical_classification, 0303 health sciences, Selenocysteine, biology, 030302 biochemistry & molecular biology, RNA-Binding Proteins, RNA, Sequence Analysis, DNA, General Medicine, Rats, Cell biology, chemistry, Chaperone (protein), biology.protein, Selenoprotein, Binding domain
Abstract: International audience; Selenocysteine (Sec) is co-translationally incorporated into selenoproteins at a reprogrammed UGA codon. In mammals, this requires a dedicated machinery comprising a stem-loop structure in the 3' UTR RNA (the SECIS element) and the specific SECIS Binding Protein 2. In this report, disorder-prediction methods and several biophysical techniques showed that ca. 70% of the SBP2 sequence is disordered, whereas the RNA binding domain appears to be folded and functional. These results are consistent with a recent report on the role of the Hsp90 chaperone for the folding of SBP2 and other functionally unrelated proteins bearing an RNA binding domain homologous to SBP2.
Published: 2009

14. The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Author: Kazutoyo Osoegawa, Finn Hallböök, Kazuyoshi Hosomichi, Hidetoshi Inoko, Naohito Takatori, Masanobu Satake, Jeremy J. Gibson-Brown, Christian M. Zmasek, Yasunori Sasakura, Yutaka Satou, Kaoru Azumi, Linda Z. Holland, Anlong Xu, Peter W. H. Holland, Zeev Pancer, Masaru Nonaka, Dan Hirose, Noriyuki Satoh, Carmela Gissi, Adam Godzik, Alice C. McHardy, Takashi Shiina, Masanori Kasahara, Takeshi Kawashima, Zbynek Kozmik, Graeme J. Roch, Larry J. Dishaw, Simona Candiani, Nancy M. Sherwood, Jordi Garcia-Fernàndez, Jun Kasamatsu, Len A. Pennacchio, Mario Pestarino, Qing Zhang, Nicholas H. Putnam, Marianne Bronner-Fraser, Shuichi Wada, Fumiko Yoshizaki, Isidore Rigoutsos, Daniel S. Rokhsar, Frédéric Brunet, Hidetoshi Saiga, Keita Yoshida, Robert Piotr Olinski, Marc Robinson-Rechavi, Èlia Benito-Gutiérrez, Masaaki Kobayashi, Thomas Butts, Kaoru Kubokawa, David E. K. Ferrier, Ayuko Kimura, Daniel Meulemans, Gary W. Litman, Tetsuro Ikuta, Ricard Albalat, Jonathan P. Rast, Vincent Laudet, Michael Schubert, Matthew J. Blow, Pavel Vopalensky, Yuzhen Ye, Pieter J. de Jong, Jr-Kai Yu, Javier Tello, Marine Biology Research Division, University of California [San Diego] (UC San Diego), University of California-University of California-Scripps Institution of Oceanography, University of Barcelona, Hokkaido University [Sapporo, Japan], United States Department of Energy, California Institute of Technology (CALTECH), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Department of Zoology, University of Cambridge [UK] (CAM), Dipartimento di Biologia, Universita degli studi di Genova, H. Lee Moffitt Cancer Center and Research Institute, All Children’s Hospital, University of St Andrews [Scotland], Department of Biology, Washington University in Saint Louis (WUSTL), Institute for Evolutionary Discovery, Partenaires INRAE, Università degli studi di Milano [Milano], Sanford Burnham Prebys Medical Discovery Institute, Uppsala University, Tokyo Metropolitan University, Tokai University School of Medicine, Hokkaido University Graduate School of Medicine, University Graduate School of Medicine, University of California [Berkeley], University of California, Okinawa Institute of Science and Technology Graduate University (OIST), The University of Tokyo, Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), University of South Florida (USF), IBM Thomas J. Watson Research Center, Max Planck Institute for Computer Science, University of Maryland Biotechnology Institute, University of Toronto, Université de Lausanne (UNIL), Northern Arizona University [Flagstaff], Shimoda Marine Research Center, University of Tsukuba, Tohoku University [Sendai], Kyoto University [Kyoto], Osaka University, Nagahama Institute of Bio-Science and Technology, Sun Yat-Sen University [Guangzhou] (SYSU), Juntendo University, and Children's Hospital Oakland Research Institute
Subjects: Branchiostoma, Letter, animal structures, [SDV]Life Sciences [q-bio], 2R hypothesis, Chordate, Mice, Transgenic, Genome, Evolution, Molecular, 03 medical and health sciences, Mice, 0302 clinical medicine, Chordata, Nonvertebrate, Branchiostoma floridae, Genetics, Gene family, Animals, Humans, [INFO]Computer Science [cs], Hox gene, Genetics (clinical), Phylogeny, 030304 developmental biology, Cephalochordate, 0303 health sciences, biology, Genes, Homeobox, biology.organism_classification, Vertebrates, 030217 neurology & neurosurgery
Abstract: Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers. The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene. This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity. However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events. In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates—a very wide phylogenetic distance. In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function. The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems. Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates.
Published: 2008

15. A high utility integrated map of the pig genome

Author: Brandy M. Marron, Patrick Chardon, Alan Archibald, Jane Rogers, Denis Milan, Carol Scott, Jonathan E. Beever, Andrew D. Jenks, Clare Bender, Gary A. Rohrer, Nick Camm, Dan J. Nonneman, Jayne Davis, Pieter J. de Jong, Angela Noon, Fengtang Yang, Sean Humphray, Richard Clark, Margarita B. Rogatcheva, Harminder Sehra, Manish Patel, Lawrence B. Schook, Stacey N. Meyers, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de radiobiologie et d'étude du génome (LREG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA), US Meat Animal Research Center, BACPAC Resources, Children's Hospital Oakland Research Institute, Roslin Institute, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), The Roslin Institute, and Biotechnology and Biological Sciences Research Council (BBSRC)
Subjects: Chromosomes, Artificial, Bacterial, carte physique, Positional cloning, MOUSE GENOME, CHROMOSOME, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Sus scrofa, Computational biology, Biology, Genome, DNA sequencing, LINKAGE MAP, 03 medical and health sciences, 0302 clinical medicine, DNA-SEQUENCE, Animals, porcin, PIGS, Cloning, Molecular, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Gene Library, Genetics, PHYSICAL MAPS, 0303 health sciences, Bacterial artificial chromosome, BAC LIBRARY, Contig, Base Sequence, Research, Physical Chromosome Mapping, food and beverages, Genome project, Chromosomes, Mammalian, COVERAGE, RADIATION HYBRID MAP, RESOLUTION, 030220 oncology & carcinogenesis, Human genome, PHYSICAL MAP, PORCINE GENOME
Abstract: A new physical map of the bovine genome has been constructed by integrating data from genetic and radiation hybrid maps, and a new bovine BAC map, with the bovine genome draft assembly., Background The domestic pig is being increasingly exploited as a system for modeling human disease. It also has substantial economic importance for meat-based protein production. Physical clone maps have underpinned large-scale genomic sequencing and enabled focused cloning efforts for many genomes. Comparative genetic maps indicate that there is more structural similarity between pig and human than, for example, mouse and human, and we have used this close relationship between human and pig as a way of facilitating map construction. Results Here we report the construction of the most highly continuous bacterial artificial chromosome (BAC) map of any mammalian genome, for the pig (Sus scrofa domestica) genome. The map provides a template for the generation and assembly of high-quality anchored sequence across the genome. The physical map integrates previous landmark maps with restriction fingerprints and BAC end sequences from over 260,000 BACs derived from 4 BAC libraries and takes advantage of alignments to the human genome to improve the continuity and local ordering of the clone contigs. We estimate that over 98% of the euchromatin of the 18 pig autosomes and the X chromosome along with localized coverage on Y is represented in 172 contigs, with chromosome 13 (218 Mb) represented by a single contig. The map is accessible through pre-Ensembl, where links to marker and sequence data can be found. Conclusion The map will enable immediate electronic positional cloning of genes, benefiting the pig research community and further facilitating use of the pig as an alternative animal model for human disease. The clone map and BAC end sequence data can also help to support the assembly of maps and genome sequences of other artiodactyls.
Published: 2007

16. Minimal ProtoHox cluster inferred from bilaterian and cnidarian Hox complements

Author: Eduard Renfer, Robert Steele, P. de Jong, Marit Flo Jensen, Baoli Zhu, P Chourrout, Rolf B. Edvardsen, Ulrich Technau, Frédéric Delsuc, Fabian Rentzsch, Daniel Chourrout, SARS International Centre for Marine Molecular Biology, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), American Hospital of Paris, Hôpital Américain de Paris, Children's Hospital Oakland Research Institute (CHORI), National Institutes of Health [Bethesda] (NIH), Department of Biology Chemistry, University of California, Irvine, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, University of California [Irvine] (UCI), and University of California-University of California
Subjects: food.ingredient, animal structures, ParaHox, Nematostella, Biology, Genome, Evolution, Molecular, Cnidaria, 03 medical and health sciences, 0302 clinical medicine, food, Gene duplication, Gene cluster, [SDE.BE.EVO]Environmental Sciences/Biodiversity and Ecology/domain_sde.be.evo, Animals, Hox gene, Gene, Phylogeny, 030304 developmental biology, Genomic organization, Homeodomain Proteins, 0303 health sciences, Multidisciplinary, Genes, Homeobox, Anatomy, Evolutionary biology, Multigene Family, 030217 neurology & neurosurgery
Abstract: Bilaterian animals have a Hox gene cluster essential for patterning the main body axis, and a ParaHox gene cluster. Comparison of Hox and ParaHox genes has led workers to postulate that both clusters originated from the duplication of an ancient cluster named ProtoHox, which contained up to four genes with at least the precursors of anterior and posterior Hox/ParaHox genes. However, the way in which genes diversified within the ProtoHox, Hox and ParaHox clusters remains unclear because no systematic study of non-bilaterian animals exists. Here we characterize the full Hox/ParaHox gene complements and genomic organization in two cnidarian species (Nematostella vectensis and Hydra magnipapillata), and suggest a ProtoHox cluster simpler than originally thought on the basis of three arguments. First, both species possess bilaterian-like anterior Hox genes, but their non-anterior genes do not appear as counterparts of either bilaterian central or posterior genes; second, two clustered ParaHox genes, Gsx and a gene related to Xlox and Cdx, are found in Nematostella vectensis; and third, we do not find clear phylogenetic support for a common origin of bilaterian Cdx and posterior genes, which might therefore have appeared after the ProtoHox cluster duplication. Consequently, the ProtoHox cluster might have consisted of only two anterior genes. Non-anterior genes could have appeared independently in the Hox and ParaHox clusters, possibly after the separation of bilaterians and cnidarians.
Published: 2006

17. Construction of a medium-density horse gene map

Author: Teri L. Lear, P. de Jong, Sead Chadi, Bhanu P. Chowdhary, Leopoldo Iannuzzi, V. Boutreux, Telhisa Hasegawa, Xavier Mata, Gaetan Guérin, Terje Raudsepp, M. Perrocheau, Baoli Zhu, Domenico Incarnato, Kei-ichi Hirota, Edmond-Paul Cribiu, Pauline Decaunes, Keith Durkin, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Molecular Cytogenetics Laboratory, Texas A&M University [College Station], Laboratory of Animal Cytogenetics and Gene Mapping, National Research Council [Italy] (CNR), Gluck Equine Research Center, University of Kentucky, Laboratory of Racing Chemistry, Utsunomiya, Laboratory of Molecular and Cellular Biology, BACPAC Resources, Children's Hospital Oakland Research Institute, AgroParisTech-Institut National de la Recherche Agronomique (INRA), and Utsunomiya University [Utsunomiya]
Subjects: Genetic Markers, Chromosomes, Artificial, Bacterial, MESH: Chromosomes, Artificial, Bacterial, Biology, MESH: Genetic Markers, Chromosomes, law.invention, Evolution, Molecular, 03 medical and health sciences, Gene mapping, law, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Animals, Humans, MESH: Animals, Horses, MESH: In Situ Hybridization, Fluorescence, MESH: Horses, Gene, In Situ Hybridization, Fluorescence, Polymerase chain reaction, MESH: Evolution, Molecular, MESH: Genome, Human, 030304 developmental biology, 0303 health sciences, MESH: Humans, Gene map, Genome, Human, 030305 genetics & heredity, Chromosome Mapping, Chromosome, General Medicine, Horse genome, Animal Science and Zoology, Human genome, MESH: Chromosomes, Primer (molecular biology), MESH: Chromosome Mapping
Abstract: International audience; A medium-density map of the horse genome (Equus caballus) was constructed using genes evenly distributed over the human genome. Three hundred and twenty-three exonic primer pairs were used to screen the INRA and the CHORI-241 equine BAC libraries by polymerase chain reaction and by filter hybridization respectively. Two hundred and thirty-seven BACs containing equine gene orthologues, confirmed by sequencing, were isolated. The BACs were localized to horse chromosomes by fluorescent in situ hybridization (FISH). Overall, 165 genes were assigned to the equine genomic map by radiation hybrid (RH) (using an equine RH(5000) panel) and/or by FISH mapping. A comparison of localizations of 713 genes mapped on the horse genome and on the human genome revealed 59 homologous segments and 131 conserved segments. Two of these homologies (ECA27/HSA8 and ECA12p/HSA11p) had not been previously identified. An enhanced resolution of conserved and rearranged chromosomal segments presented in this study provides clarification of chromosome evolution history.
Published: 2006

18. Construction of a medium density equine gene map

Author: PERROCHEAU, M, BOUTREUX, V, Chadi, Sead, Mata, Xavier, DECAUNES, Pauline, RAUDSEPP, T, DURKIN, K, INCARNATO, D, IANNUZZI, L, LEAR, TL, HIROTA, K, HASEGAWA, T, ZHU, B, DE JONG, P, Cribiu, Edmond, CHOWDHARY, BP, Guérin, Gerard, Unité de recherche Génétique Biochimique et Cytogénétique (LGBC), Institut National de la Recherche Agronomique (INRA), Texas A&M University System, ISPAAM, Laboratory of Animal Cytogenetics and Gene Mapping, Consiglio Nazionale delle Ricerche [Roma] (CNR), University of Kentucky, Department of Molecular Genetics, Japan Racing Association, BACPAC Resources, and Children's Hospital Oakland Research Institute
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, COMPARATIVE MAPPING, GENE MAPPING, HORSE, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2006

19. A physical map of the bovine genome

Author: Laurent Schibler, Tad S. Sonstegard, Warren M Snelling, Ian Bosdet, Marco A. Marra, Ross L. Tellam, Curtis P Van Tassell, Rudiger Brauning, Frank W. Nicholas, John C. McEwan, Brenda M. Murdoch, Pieter J. de Jong, Annelie Everts-van der Wind, Kazutoyo Osoegawa, Alice Roy, Natasja Wye, Stephen S. Moore, Jeremy F. Taylor, John L. Williams, John W. Keele, Loren C. Skow, Oliver C. Jann, Colette A. Abbey, Sandrine Floriot, Gary L. Bennett, Licia Silveri, Shaying Zhao, Mathieu Gautier, Marcos M Costa, Readman Chiu, Timothy P. L. Smith, A. M. Crawford, Stephanie D. McKay, David L. Adelson, Mekki Boussaha, Steven J.M. Jones, Robert D. Schnabel, Steven M. Kappes, Jacqueline E. Schein, Denis M. Larkin, Alexandre Rodrigues Caetano, Hanni Salih, Clare A. Gill, André Eggen, Carrie Mathewson, Matthew Hobbs, Jan Aerts, Brian P. Dalrymple, Robert A. Holt, George S. Yang, James E. Womack, Lakshmi K. Matukumalli, Ronnie D. Green, Harris A. Lewin, United States Department of Agriculture (USDA), British Columbia Cancer Agency, University of Sydney, Texas A&M University System, Roslin Institute, Unité de recherche Génétique Biochimique et Cytogénétique (LGBC), Institut National de la Recherche Agronomique (INRA), Agresearch Ltd, Parque Estaçao Biologica, Livestock Industries, Department of Animal Sciences, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, USDA-ARS : Agricultural Research Service, Children's Hospital Oakland Research Institute, Institute for Genomic Biology, Department of Agricultural, Food and Nutritional Science, University of Alberta, Consortium national de recherche en génomique, University of Missouri [Columbia] (Mizzou), University of Missouri System, Istituto di Zootecnica, Università cattolica del Sacro Cuore [Milano] (Unicatt), Parco Tecnologico Padano, Polo Universitario, The Institute for Genomic Research (TIGR), University of Georgia [USA], Warren M. Snelling, US Meat Animal Research Center, Readman Chiu, Genome Sciences Centre, Jacqueline E. Schein, Genome Sciences Centre, Matthew Hobbs, Cooperative Research Centre for Innovative Dairy Products, Colette A. Abbey, Texas A & M University, David L. Adelson, Texas A & M University, Jan Aerts, Roslin Institute, Gary L. Bennett, US Meat Animal Research Center, Ian E. Bosdet, Genome Sciences Centre, Mekki Boussaha, INRA, Rudiger Brauning, AgResearch Invermay, Alexandre Rodrigues Caetano, Embrapa Recursos Genéticos e Biotecnologia, Marcos Mota do Carmo Costa, Embrapa Recursos Genéticos e Biotecnologia, Allan M. Crawford, AgResearch Invermay, Brian P. Dalrymple, CSIRO Livestock Industries, André Eggen, INRA, Annelie Everts van der Wind, University of Illinois at Urbana, Sandrine Floriot, INRA, Mathieu Gautier, INRA, Clare A. Gill, Texas A & M University, Ronnie D. Green, USDA-ARS, Robert Holt, Genome Sciences Centre, Oliver Jann, Roslin Institute, Steven J. M Jones, Genome Sciences Centre, Steven M. Kappes, USDA-ARS, John W. Keele, US Meat Animal Research Center, Pieter J. de Jong, Children's Hospital Oakland Research Institut, Denis M. Larkin, University of Illinois at Urbana, Harris A. Lewin, University of Illinois at Urbana, John C. McEwan, AgResearch Invermay, Stephanie McKay, University of Alberta, Marco A. Marra, Genome Sciences Centre, Carrie A. Mathewson, Genome Sciences Centre, Lakshmi K. Matukumalli USDA ARS, Stephen S. Moore, University of Alberta, Brenda Murdoch, University of Alberta, Frank W. Nicholas, Cooperative Research Centre for Innovative Dairy Products, Kazutoyo Osoegawa, Children's Hospital Oakland Research Institut, Alice Roy, Genoscope, Hanni Salih, Texas A & M University, Laurent Schibler, INRA, Robert D. Schnabel, Animal Science Research Center, Licia Silveri, Instituto di Zootecnica Università Cattolica del S. Cuore, Loren C. Skow, Texas A & M University, Timothy P. L. Smith, US Meat Animal Research Center, Tad S. Sonstegard, USDA, Jeremy F. Taylor, Animal Science Research Center, Ross Tellam, CSIRO Livestock Industries, Curtis P. Van Tassell USDA ARS, John LWilliams USDA ARS, James E. Womack, Texas A & M University, Natasja H. Wye, Genome Sciences Centre, George Yang, Genome Sciences Centre, and Shaying Zhao, The Institute for Genomic Research.
Subjects: Genetic Markers, Cancer genome sequencing, Chromosomes, Artificial, Bacterial, bovin, carte physique, Genotype, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Sequence assembly, Deoxyribonuclease HindIII, Biology, Genome, 03 medical and health sciences, Gene Order, Animals, Humans, Genoma, 030304 developmental biology, Bovino, 2. Zero hunger, Genetics, Radiation Hybrid Mapping, 0303 health sciences, Bacterial artificial chromosome, Base Sequence, Genome, Human, Shotgun sequencing, Research, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Genome project, Chromosomes, Mammalian, 040201 dairy & animal science, Pedigree, Bovine genome, Cattle, Human genome, Sequence Alignment
Abstract: A new physical map of the bovine genome has been constructed by integrating data from genetic and radiation hybrid maps, and a new bovine BAC map, with the bovine genome draft assembly., Background Cattle are important agriculturally and relevant as a model organism. Previously described genetic and radiation hybrid (RH) maps of the bovine genome have been used to identify genomic regions and genes affecting specific traits. Application of these maps to identify influential genetic polymorphisms will be enhanced by integration with each other and with bacterial artificial chromosome (BAC) libraries. The BAC libraries and clone maps are essential for the hybrid clone-by-clone/whole-genome shotgun sequencing approach taken by the bovine genome sequencing project. Results A bovine BAC map was constructed with HindIII restriction digest fragments of 290,797 BAC clones from animals of three different breeds. Comparative mapping of 422,522 BAC end sequences assisted with BAC map ordering and assembly. Genotypes and pedigree from two genetic maps and marker scores from three whole-genome RH panels were consolidated on a 17,254-marker composite map. Sequence similarity allowed integrating the BAC and composite maps with the bovine draft assembly (Btau3.1), establishing a comprehensive resource describing the bovine genome. Agreement between the marker and BAC maps and the draft assembly is high, although discrepancies exist. The composite and BAC maps are more similar than either is to the draft assembly. Conclusion Further refinement of the maps and greater integration into the genome assembly process may contribute to a high quality assembly. The maps provide resources to associate phenotypic variation with underlying genomic variation, and are crucial resources for understanding the biology underpinning this important ruminant species so closely associated with humans.
Published: 2007

20. Gender, body mass index and rheumatoid arthritis disease activity: Results from the QUEST-RA study

Author: Jawaheer, D., Olsen, J., Lahiff, M., Forsberg, S., Lähteenmäki, J., Da Silveira, I. G., Rocha, F. A., Laurindo, I. M. M., Da Mota, L. M. H., Drosos, A. A., Murphy, E., Sheehy, C., Quirke, E., Cutolo, M., Rexhepi, S., Dadoniene, J., Verstappen, S. M. M., Sokka, T., Toloza, S., Aguero, S., Barrera, S. O., Retamozo, S., Alba, P., Lascano, C., Babini, A., Albiero, E., Pinheiro, G. R. C., Lazovskis, J., Hetland, M. L., Ørnbjerg, L., Hørslev-Petersen, K., Hansen, T. M., Knudsen, L. S., Hamoud, H., Sobhy, M., Fahmy, A., Magdy, M., Aly, H., Saeid, H., Nagm, A., Fathi, N. A., Abda, E., Ebraheam, Z., Müller, R., Kuuse, R., Tammaru, M., Kallikorm, R., Peets, T., Otsa, K., Laas, K., Valter, I., Mäkinen, H., Immonen, K., Luukkainen, R., Gossec, L., Dougados, M., Maillefert, J. F., Combe, B., Sibilia, J., Exarchou, S., Moutsopoulos, H. M., Tsirogianni, A., Skopouli, F. N., Mavrommati, M., Herborn, G., Rau, R., Alten, R., Pohl, C., Burmester, G. R., Marsmann, B., Géher, P., Rojkovich, B., Bresnihan, B., Minnock, P., Devlin, J., Alraqi, S., Aggarwal, A., Pandya, S., Sharma, B., Cazzato, M., Bombardieri, S., Ferraccioli, G., Morelli, A., Salaffi, F., Stancati, A., Yamanaka, H., Nakajima, A., Fukuda, W., Shono, E., Oyoo, O., Rexhepi, M., Andersone, D., Stropuviene, S., Baranauskaite, A., Najia Hajjaj-Hassouni, Benbouazza, K., Allali, F., Bahiri, R., Amine, B., Jacobs, J. W. G., Huisman, M., Hoekstra, M., Haugeberg, G., Gjelberg, H., Sierakowski, S., Majdan, M., Romanowski, W., Tlustochowicz, W., Kapolka, D., Sadkiewicz, S., Zarowny-Wierzbinska, D., Ionescu, R., Predeteanu, D., Karateev, D., Luchikhina, E., Chichasova, N., Badokin, V., Skakic, V., Dimic, A., Nedovic, J., Stankovic, A., Naranjo, A., Rodríguez-Lozano, C., Calvo-Alen, J., Belmonte, M., Baecklund, E., Henrohn, D., Oding, R., Liveborn, M., Holmqvist, A. -C, Gogus, F., Tunc, R., Celic, S., Badsha, H., Mofti, A., Taylor, P., Mcclinton, C., Woolf, A., Chorghade, G., Choy, E., Kelly, S., Pincus, T., Yazici, Y., Bergman, M., Craig-Muller, J., Kautiainen, H., Swearingen, C., University of California Los Angeles, University of California Berkeley, North Karelia Central Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Universidade Federal do Ceará, Universidade Estadual Paulista (UNESP), Hospital Universitário de Brasília, University of Ioannina Ioannina, Waterford Regional Hospital, Connolly Hospital, University of Genova, Rheumatology Department, Vilnius University, University Medical Centre Utrecht, Jyväskylä Central Hospital, Medcare Oy, Hospital Oakland Research Institute, Hospital San Juan Bautista, Hospital of Cordoba, Universidade do Estado do Rio de Janeiro (UERJ), Riverside Professional Centre, Copenhagen University Hospital at Hvidovre, King Christian the Xth Hospital, Copenhagen University Hospital at Herlev, Al-Azhar University, Assiut University Hospital, Abo Sohage University Hospital, Tartu University Hospital, East-Tallinn Central Hospital, Centre for Clinical and Basic Research, Satakunta Central Hospital, Hôpital Cochin, INSERM U887, Hôpital Lapeyronie, Hôpital Hautepierre, National University of Athens, Euroclinic Hospital, Evangelisches Fachkrankenhaus, Schlosspark-Klinik, University Medicine Berlin, Semmelweis University of Medical Sciences, Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, St. Vincent University Hospital, Our Lady's Hospice, Vedanta Institiute of Medical Sciences, Jaipur Hospital, Santa Chiara Hospital, Catholic University of Sacred Heart, University of Ancona, Tokyo Women's Medical University, Kyoto First Red Cross Hospital, Shono Rheumatism Clinic, Kenyatta Hospital, Pauls Stradina Clinical University Hospital, Kaunas University Hospital, El Ayachi Hospital Mohamed Vth Souissi University, Sint Franciscus Gasthuis Hospital, Medisch Spectrum Twente, Sørlandet Hospital, Medical University in Bialystok, Medical University of Lublin, Poznan Rheumatology Centre in Srem, Military Institute of Medicine, Silesian Hospital for Rheumatology and Rehabilitation in Ustron Slaski, Szpital Wojewodzki im. Jana Biziela, Wojewodzki Zespol Reumatologiczny im. dr Jadwigi Titz-Kosko, Spitalul Clinic Sf Maria, Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow Medical Academy, Russian Medical Academy of Postgraduate Education, Rheumatology Institut, Hospital de Gran Canaria Dr. Negrin, Hospital Sierrallana Ganzo, Hospital General de Castellón, Uppsala University Hospital, Centrallasarettet, Hudiksvall Medical Clinic, Gazi University Medical Faculty, Meram Medical Faculty, Cerrahpasa Medic Faculty, Dubai Bone and Joint Centre, American Hospital Dubai, Charing Cross Hospital, Royal Cornwall Hospital, Kings College Hospital, Vanderbilt University, NYU Hospital for Joint Diseases, Taylor Hospital, Centra Care Clinic, University of Arkansas for Medical Sciences, and New York University Hospital for Joint Diseases
Subjects: Bmi, Gender, Disease activity, Rheumatoid arthritis
Abstract: Made available in DSpace on 2022-04-28T18:56:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-01 Objective: To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods: Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results: A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion: BMI appears to be associated with RA disease activity in women, but not in men. © Copyright Clinical and Experimental Rheumatology 2010. University of California Los Angeles, Los Angeles, CA University of California Berkeley, Berkeley, CA North Karelia Central Hospital, Joensuu Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre Universidade Federal do Ceará, Fortaleza Universidade Estadual de São Paulo, São Paulo Hospital Universitário de Brasília, Brasilia University of Ioannina Ioannina Waterford Regional Hospital, Waterford Connolly Hospital, Dublin University of Genova, Genova Rheumatology Department, Pristine Institute of Experimental and Clinical Medicine Vilnius University, Vilnius University Medical Centre Utrecht, Utrecht Jyväskylä Central Hospital, Jyväskylä Medcare Oy, Äänekoski Hospital Oakland Research Institute, Oakland, CA Hospital San Juan Bautista, Catamarca Hospital of Cordoba, Cordoba Universidade do Estado do Rio de Janeiro, Rio de Janeiro Riverside Professional Centre, Sydney, NS Copenhagen University Hospital at Hvidovre, Hvidovre King Christian the Xth Hospital, Gråsten Copenhagen University Hospital at Herlev, Herlev Al-Azhar University, Cairo Assiut University Hospital, Assiut Abo Sohage University Hospital, Sohage Tartu University Hospital, Tartu East-Tallinn Central Hospital, Tallinn Centre for Clinical and Basic Research, Tallinn Satakunta Central Hospital, Rauma University René Descartes Hôpital Cochin, Paris Dijon University Hospital University of Burgundy INSERM U887, Dijon Hôpital Lapeyronie, Montpellier Hôpital Hautepierre, Strasbourg School of Medicine National University of Athens, Athens Euroclinic Hospital, Athens Evangelisches Fachkrankenhaus, Ratingen Schlosspark-Klinik, Berlin University Medicine Berlin, Berlin Semmelweis University of Medical Sciences, Budapest Ilona Újfalussy Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Budapest St. Vincent University Hospital, Dublin Our Lady's Hospice, Dublin Department of Immunology, Lucknow Vedanta Institiute of Medical Sciences, Ahmedabad Department of Immunology Jaipur Hospital Santa Chiara Hospital, Pisa Catholic University of Sacred Heart, Rome University of Ancona, Ancona Institute of Rheumatology Tokyo Women's Medical University, Tokyo Department of Rheumatology Kyoto First Red Cross Hospital, Kyoto Shono Rheumatism Clinic, Fukuoka Kenyatta Hospital, Nairobi Pauls Stradina Clinical University Hospital, Riga Kaunas University Hospital, Kaunas El Ayachi Hospital Mohamed Vth Souissi University, Rabat Sint Franciscus Gasthuis Hospital, Rotterdam Medisch Spectrum Twente, Enschede Sørlandet Hospital, Kristiansand Medical University in Bialystok, Bialystok Medical University of Lublin, Lublin Poznan Rheumatology Centre in Srem, Srem Military Institute of Medicine, Warsaw Silesian Hospital for Rheumatology and Rehabilitation in Ustron Slaski, Ustroñ Slaski Szpital Wojewodzki im. Jana Biziela, Bydgoszcz Wojewodzki Zespol Reumatologiczny im. dr Jadwigi Titz-Kosko, Sopot Spitalul Clinic Sf Maria, Bucharest Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow Moscow Medical Academy, Moscow Russian Medical Academy of Postgraduate Education, Moscow Rheumatology Institut, Niska Banja Hospital de Gran Canaria Dr. Negrin, Las Palmas Hospital Sierrallana Ganzo, Torrelavega Hospital General de Castellón, Castellón Uppsala University Hospital, Uppsala Centrallasarettet, Västerås Hudiksvall Medical Clinic, Hudiksvall Gazi University Medical Faculty, Ankara Meram Medical Faculty, Konya Cerrahpasa Medic Faculty, Istanbul Dubai Bone and Joint Centre, Dubai American Hospital Dubai, Dubai Charing Cross Hospital, London Royal Cornwall Hospital, Truro Kings College Hospital, London Vanderbilt University, Nashville, TN NYU Hospital for Joint Diseases, New York, NY Taylor Hospital, Ridley Park, PA Centra Care Clinic, St. Cloud, MN University of Arkansas for Medical Sciences, Little Rock, AR New York University Hospital for Joint Diseases, New York, NY Universidade Estadual de São Paulo, São Paulo

21. Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions.

Author: Noble JA
Subjects: Humans, Genotype, History, 20th Century, History, 21st Century, Risk Factors, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 history, Diabetes Mellitus, Type 1 immunology, Genetic Predisposition to Disease history, HLA Antigens genetics, HLA Antigens history, HLA Antigens immunology
Abstract: More than 50 years have elapsed since the association of human leukocyte antigens (HLA) with type 1 diabetes (T1D) was first reported. Since then, methods for identification of HLA have progressed from cell based to DNA based, and the number of recognized HLA variants has grown from a few to tens of thousands. Current genotyping methodology allows for exact identification of all HLA-encoding genes in an individual's genome, with statistical analysis methods evolving to digest the enormous amount of data that can be produced at an astonishing rate. The HLA region of the genome has been repeatedly shown to be the most important genetic risk factor for T1D, and the original reported associations have been replicated, refined, and expanded. Even with the remarkable progress through 50 years and over 5,000 reports, a comprehensive understanding of all effects of HLA on T1D remains elusive. This report represents a summary of the field as it evolved and as it stands now, enumerating many past and present challenges, and suggests possible paradigm shifts for moving forward with future studies in hopes of finally understanding all the ways in which HLA influences the pathophysiology of T1D., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Noble.)
Published: 2024
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22. Non-invasive prenatal testing of beta-hemoglobinopathies using next generation sequencing, in-silico sequence size selection, and haplotyping.

Author: Erlich HA, Ko L, Lee J, Eaton K, Calloway CD, Lal A, Das R, Jamwal M, Lopez-Pena C, and Mack SJ
Subjects: Humans, Female, Pregnancy, Prenatal Diagnosis methods, beta-Thalassemia genetics, beta-Thalassemia diagnosis, Noninvasive Prenatal Testing, beta-Globins genetics, Genotype, Hemoglobinopathies genetics, Hemoglobinopathies diagnosis, Anemia, Sickle Cell genetics, Anemia, Sickle Cell diagnosis, High-Throughput Nucleotide Sequencing, Haplotypes, Polymorphism, Single Nucleotide
Abstract: Aim: To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing., Methods: We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF., Results: We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software., Conclusion: The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.
Published: 2024

23. NKp44/HLA-DP-dependent regulation of CD8 effector T cells by NK cells.

Author: Padoan B, Casar C, Krause J, Schultheiss C, Baumdick ME, Niehrs A, Zecher BF, Pujantell M, Yuki Y, Martin M, Remmerswaal EBM, Dekker T, van der Bom-Baylon ND, Noble JA, Carrington M, Bemelman FJ, van Lier RAW, Binder M, Gagliani N, Bunders MJ, and Altfeld M
Subjects: Humans, Cytomegalovirus immunology, Haplotypes, Lymphocyte Activation immunology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Natural Cytotoxicity Triggering Receptor 2 metabolism
Abstract: Although natural killer (NK) cells are recognized for their modulation of immune responses, the mechanisms by which human NK cells mediate immune regulation are unclear. Here, we report that expression of human leukocyte antigen (HLA)-DP, a ligand for the activating NK cell receptor NKp44, is significantly upregulated on CD8 + effector T cells, in particular in human cytomegalovirus (HCMV) + individuals. HLA-DP + CD8 + T cells expressing NKp44-binding HLA-DP antigens activate NKp44 + NK cells, while HLA-DP + CD8 + T cells not expressing NKp44-binding HLA-DP antigens do not. In line with this, frequencies of HLA-DP + CD8 + T cells are increased in individuals not encoding for NKp44-binding HLA-DP haplotypes, and contain hyper-expanded CD8 + T cell clones, compared to individuals expressing NKp44-binding HLA-DP molecules. These findings identify a molecular interaction facilitating the HLA-DP haplotype-specific editing of HLA-DP + CD8 + T cell effector populations by NKp44 + NK cells and preventing the generation of hyper-expanded T cell clones, which have been suggested to have increased potential for autoimmunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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24. Urine steroid metabolomics as a diagnostic tool in primary aldosteronism.

Author: Prete A, Lang K, Pavlov D, Rhayem Y, Sitch AJ, Franke AS, Gilligan LC, Shackleton CHL, Hahner S, Quinkler M, Dekkers T, Deinum J, Reincke M, Beuschlein F, Biehl M, and Arlt W
Subjects: Adult, Humans, Steroids, Mass Spectrometry, Aldosterone metabolism, Mutation, G Protein-Coupled Inwardly-Rectifying Potassium Channels genetics, G Protein-Coupled Inwardly-Rectifying Potassium Channels metabolism, Hyperaldosteronism diagnosis, Hyperaldosteronism genetics, Hyperaldosteronism metabolism, Adrenocortical Adenoma genetics, Adenoma diagnosis, Adrenal Cortex Neoplasms genetics
Abstract: Primary aldosteronism (PA) causes 5-10% of hypertension cases, but only a minority of patients are currently diagnosed and treated because of a complex, stepwise, and partly invasive workup. We tested the performance of urine steroid metabolomics, the computational analysis of 24-hour urine steroid metabolome data by machine learning, for the identification and subtyping of PA. Mass spectrometry-based multi-steroid profiling was used to quantify the excretion of 34 steroid metabolites in 24-hour urine samples from 158 adults with PA (88 with unilateral PA [UPA] due to aldosterone-producing adenomas [APAs]; 70 with bilateral PA [BPA]) and 65 sex- and age-matched healthy controls. All APAs were resected and underwent targeted gene sequencing to detect somatic mutations associated with UPA. Patients with PA had increased urinary metabolite excretion of mineralocorticoids, glucocorticoids, and glucocorticoid precursors. Urine steroid metabolomics identified patients with PA with high accuracy, both when applied to all 34 or only the three most discriminative steroid metabolites (average areas under the receiver-operating characteristics curve [AUCs-ROC] 0.95-0.97). Whilst machine learning was suboptimal in differentiating UPA from BPA (average AUCs-ROC 0.65-0.73), it readily identified APA cases harbouring somatic KCNJ5 mutations (average AUCs-ROC 0.79-85). These patients showed a distinctly increased urine excretion of the hybrid steroid 18-hydroxycortisol and its metabolite 18-oxo-tetrahydrocortisol, the latter identified by machine learning as by far the most discriminative steroid. In conclusion, urine steroid metabolomics is a non-invasive candidate test for the accurate identification of PA cases and KCNJ5-mutated APAs., Competing Interests: Declaration of Competing Interest The authors declare no competing interests in relation to this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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25. Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome.

Author: Borja MS, Hammerson B, Tang C, Juarez-Serrano L, Savinova OV, Harris WS, Oda MN, and Shearer GC
Subjects: Humans, Apolipoprotein A-I therapeutic use, Cholesterol, HDL, Double-Blind Method, Fatty Acids, Omega-3 pharmacology, Fatty Acids, Omega-3 therapeutic use, Niacin therapeutic use, Metabolic Syndrome drug therapy
Abstract: HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers., Competing Interests: MNO has an affiliation with Seer Biologics, Inc. MNO is a founder of and owns a significant stake in Seer Biologics, Inc., which could stand to benefit from the research described here. This in no way influenced the thoroughness, stringency, interpretation and presentation of this manuscript’s content. This affiliation does not alter the author’s adherence to PLOS ONE policies on sharing data and materials. At the time of the parent study, GCS was supported by GlaxSmithKline. The other authors declare no competing interests., (Copyright: © 2024 Borja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2024
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26. Complete HLA genotyping of type 1 diabetes patients and controls from Mali reveals both expected and novel disease associations.

Author: Noble JA, Besançon S, Sidibé AT, Rozemuller EH, Rijkers M, Dadkhodaie F, de Bruin H, Kooij J, Martin HRN, Ogle GD, and Mack SJ
Subjects: Humans, Genotype, HLA-C Antigens genetics, HLA-DRB1 Chains genetics, Gene Frequency, Mali, Alleles, Haplotypes, HLA-B Antigens genetics, HLA-A Antigens genetics, Diabetes Mellitus, Type 1 genetics
Abstract: HLA genotyping was performed on 99 type 1 diabetes (T1D) patients and 200 controls from Mali. Next-generation sequencing of the classical HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci revealed strong T1D association for all loci except HLA-C and -DPA1. Class II association is stronger than class I association, with most observed associations predisposing or protective as expected based on previous studies. For example, HLA-DRB1*03:01, HLA-DRB1*09:01, and HLA-DRB1*04:05 predispose for T1D, whereas HLA-DRB1*15:03 is protective. HLA-DPB1*04:02 (OR = 12.73, p = 2.92 × 10 -05 ) and HLA-B*27:05 (OR = 21.36, p = 3.72 × 10 -05 ) appear highly predisposing, although previous studies involving multiple populations have reported HLA-DPB1*04:02 as T1D-protective and HLA-B*27:05 as neutral. This result may reflect the linkage disequilibrium between alleles on the extended HLA-A*24:02~HLA-B*27:05~HLA-C*02:02~HLA-DRB1*04:05~HLA-DRB4*01:03~HLA-DQB1*02:02~HLA-DQA1*02:01~HLA-DPB1*04:02~HLA-DPA1*01:03 haplotype in this population rather than an effect of either allele itself. Individual amino acid (AA) analyses are consistent with most T1D association attributable to HLA class II rather than class I in this data set. AA-level analyses reveal previously undescribed differences of the HLA-C locus from the HLA-A and HLA-B loci, with more polymorphic positions, spanning a larger portion of the gene. This may reflect additional mechanisms for HLA-C to influence T1D risk, for example, through expression differences or through its role as the dominant ligand for killer cell immunoglobulin-like receptors (KIR). Comparison of these data to those from larger studies and on other populations may facilitate T1D prediction and help elucidate elusive mechanisms of how HLA contributes to T1D risk and autoimmunity., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)
Published: 2024
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27. Pre-pregnancy gene expression signatures are associated with subsequent improvement/worsening of rheumatoid arthritis during pregnancy.

Author: Wright M, Smed MK, Nelson JL, Olsen J, Hetland ML, Jewell NP, Zoffmann V, and Jawaheer D
Subjects: Pregnancy, Humans, Female, Prospective Studies, Gene Expression Profiling, Biomarkers, Transcriptome, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid drug therapy
Abstract: Background: While many women with rheumatoid arthritis (RA) improve during pregnancy and others worsen, there are no biomarkers to predict this improvement or worsening. In our unique RA pregnancy cohort that includes a pre-pregnancy baseline, we have examined pre-pregnancy gene co-expression networks to identify differences between women with RA who subsequently improve during pregnancy and those who worsen., Methods: Blood samples were collected before pregnancy (T0) from 19 women with RA and 13 healthy women enrolled in our prospective pregnancy cohort. RA improvement/worsening between T0 and 3rd trimester was assessed by changes in the Clinical Disease Activity Index (CDAI). Pre-pregnancy expression profiles were examined by RNA sequencing and differential gene expression analysis. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules correlated with the improvement/worsening of RA during pregnancy and to assess their functional relevance., Results: Of the 19 women with RA, 14 improved during pregnancy (RA improved ) while 5 worsened (RA worsened ). At the T0 baseline, however, the mean CDAI was similar between the two groups. WGCNA identified one co-expression module related to B cell function that was significantly correlated with the worsening of RA during pregnancy and was significantly enriched in genes differentially expressed between the RA improved and RA worsened groups. A neutrophil-related expression signature was also identified in the RA improved group at the T0 baseline., Conclusion: The pre-pregnancy gene expression signatures identified represent potential biomarkers to predict the subsequent improvement/worsening of RA during pregnancy, which has important implications for the personalized treatment of RA during pregnancy., (© 2023. BioMed Central Ltd., part of Springer Nature.)
Published: 2023
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28. The Effect of Zinc Biofortified Wheat Produced via Foliar Application on Zinc Status: A Randomized, Controlled Trial in Indian Children.

Author: Signorell C, Kurpad AV, Pauline M, Shenvi S, Mukhopadhyay A, King JC, Zimmermann MB, and Moretti D
Abstract: Background: Agronomic zinc biofortification of wheat by foliar application increases wheat zinc content and total zinc absorption in humans., Objectives: To assess the effect of agronomically biofortified whole wheat flour (BFW) on plasma zinc (PZC) compared with a postharvest fortified wheat (PHFW) and unfortified control wheat (CW) when integrated in a midday school meal scheme., Methods: We conducted a 20-wk double-blind intervention trial in children (4-12 y, n = 273) individually randomly assigned to 3 groups to receive a daily school lunch consisting of 3 chapattis prepared with the 3 different wheat flour types. Measurements of anthropometry, blood biochemistry, and leukocyte DNA strand breaks were conducted. We applied sparse serial sampling to monitor PZC over time, and analysis was performed using linear mixed-effects models., Results: Mean zinc content in BFW, PHFW, and CW were 48.0, 45.1, and 21.2 ppm, respectively (P < 0.001). Mean (standard deviation) daily zinc intakes in the study intervention in BFW, PHFW, and CW groups were 4.4 (1.6), 5.9 (1.9) and 2.6 (0.6) mg Zn/d, respectively, with intake in groups PHFW and BFW differing from CW (P < 0.001) but no difference between BFW and PHFW. There were no time effect, group difference, or group × time interaction in PZC. Prevalence of zinc deficiency decreased in the BFW (from 14.1%-11.2%), PHFW (from 8.9%-2.3%), and CW (9.8%-8.8%) groups, but there was no time × treatment interaction in the prevalence of zinc deficiency (P = 0.191). Compliance with consuming the study school meals was associated with PZC (P = 0.006). DNA strand breaks were not significantly associated with PZC (n = 51; r = 0.004, P = 0.945)., Conclusions: Consumption of either PHFW or BFW provided an additional ∼1.8 to 3.3 mg Zn/d, but it did not affect PZC or zinc deficiency, growth, or DNA strand breaks. This trial was registered on clinicaltrials.gov as NCT02241330 and ctri.nic.in as CTRI/2015/06/005913., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)
Published: 2023
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29. Protective role of CFTR during fungal infection of cystic fibrosis bronchial epithelial cells with Aspergillus fumigatus .

Author: Illek B, Fischer H, Machen TE, Hari G, Clemons KV, Sass G, Ferreira JAG, and Stevens DA
Subjects: Aspergillus fumigatus, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Chlorides, Epithelial Cells, Cystic Fibrosis complications, Gliotoxin, Mycoses
Abstract: Lung infection with the fungus Aspergillus fumigatus ( Af ) is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function. We established a fungal epithelial co-culture model to examine the impact of Af infection on CF bronchial epithelial barrier function using Af strains 10AF and AF293-GFP, and the CFBE41o- cell line homozygous for the F508del mutation with (CF +CFTR ) and without (CF) normal CFTR expression. Following exposure of the epithelial surface to Af conidia, formation of germlings (early stages of fungal growth) was detected after 9-12 hours and hyphae (mature fungal growth) after 12-24 hours. During fungal morphogenesis, bronchial epithelial cells showed signs of damage including rounding, and partial detachment after 24 hours. Fluorescently labeled conidia were internalized after 6 hours and more internalized conidia were observed in CF compared to CF +CFTR cells. Infection of the apical surface with 10AF conidia, germlings, or hyphae was performed to determine growth stage-specific effects on tight junction protein zona occludens protein 1 (ZO-1) expression and transepithelial electrical resistance (TER). In response to infection with conidia or germlings, epithelial barrier function degraded time-dependently (based on ZO-1 immunofluorescence and TER) with a delayed onset in CF +CFTR cell monolayers and required viable fungi and apical application. Infection with hyphae caused an earlier onset and faster rate of decline in TER compared to conidia and germlings. Gliotoxin, a major Af virulence factor, caused a rapid decline in TER and induced a transient chloride secretory response in CF +CFTR but not CF cells. Our findings suggest growth and internalization of Af result in deleterious effects on bronchial epithelial barrier function that occurred more rapidly in the absence of CFTR. Bronchial epithelial barrier breakdown was time-dependent and morphotype-specific and mimicked by acute administration of gliotoxin. Our study also suggests a protective role for CFTR by turning on CFTR-dependent chloride transport in response to gliotoxin, a mechanism that will support mucociliary clearance, and could delay the loss of epithelial integrity during fungal development in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Illek, Fischer, Machen, Hari, Clemons, Sass, Ferreira and Stevens.)
Published: 2023
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30. Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants.

Author: Butler-Laporte G, Auckland K, Noor Z, Kabir M, Alam M, Carstensen T, Wojcik GL, Chong AY, Pomilla C, Noble JA, McDevitt SL, Smits G, Wareing S, van der Klis FR, Jeffery K, Kirkpatrick BD, Sirima S, Madhi S, Elliott A, Richards JB, Hill AV, Duggal P, Sandhu MS, Haque R, Petri WA Jr, and Mentzer AJ
Abstract: Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individuals DPB1*04:01 was associated with higher HBV antibody responses (p=4.5×10 -30 ). The underlying mechanism is a result of higher affinity binding of HBV surface antigen epitopes to DPB1*04:01 dimers. This is likely a result of evolutionary pressure at the HBV surface antigen 'a-determinant' segment incurring VEM specific to HBV. Prioritizing pre-S isoform HBV vaccines may tackle the rise of HBV vaccine evasion., Competing Interests: Competing interests: JBR’s institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline and Biogen for projects unrelated to this research. He is the CEO of 5 Prime Sciences Inc (www.5primesciences.com).
Published: 2023
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31. Pregnancy-associated systemic gene expression compared to a pre-pregnancy baseline, among healthy women with term pregnancies.

Author: Wright ML, Goin DE, Smed MK, Jewell NP, Nelson JL, Olsen J, Hetland ML, Zoffmann V, and Jawaheer D
Subjects: Humans, Pregnancy, Female, Prospective Studies, Pregnancy Trimester, Third, Sequence Analysis, RNA, Gene Expression, Pregnancy Complications genetics
Abstract: Background: Pregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies., Methods: Blood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline., Results: Numerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes., Conclusion: Compared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a "normal" reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wright, Goin, Smed, Jewell, Nelson, Olsen, Hetland, Zoffmann and Jawaheer.)
Published: 2023
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32. Multiplex recombinase polymerase amplification for high-risk and low-risk type HPV detection, as potential local use in single tube.

Author: Wongsamart R, Bhattarakasol P, Chaiwongkot A, Wongsawaeng D, Okada PA, Palaga T, Leelahavanichkul A, Khovidhunkit W, Dean D, and Somboonna N
Subjects: Female, Humans, Recombinases, Early Detection of Cancer, Nucleotidyltransferases, Papillomaviridae genetics, Sensitivity and Specificity, DNA, Viral genetics, Uterine Cervical Neoplasms diagnosis, Papillomavirus Infections diagnosis
Abstract: High rates of new cervical cancer cases and deaths occur in low- and middle-income countries yearly, and one reason was found related to limitation of regular cervical cancer screening in local and low-resource settings. HPV has over 150 types, yet certain 14-20 high-risk and 13-14 low-risk types are common, and, thus, most conventional HPV nucleic acid assays, for examples, Cobas 4800 HPV test (Roche Diagnostics, New Jersey, USA) and REBA HPV-ID (Molecules and Diagnostics, Wonju, Republic of Korea) were developed to cover these types. We thereby utilized bioinformatics combined with recent isothermal amplification technique at 35-42 °C to firstly describe multiplex recombinase polymerase amplification assay that is specific to these common 20 high-risk and 14 low-risk types, and also L1 and E6/E7 genes that target different stages of cervical cancer development. Multiplex primer concentrations and reaction incubation conditions were optimized to allow simultaneous two gene detections at limit of detection of 1000 copies (equivalent to 2.01 fg) for L1 and 100 copies (0.0125 fg) for E6/E7, respectively. The assay was validated against urogenital and other pathogens, normal flora, and human control. In 130 real clinical sample tests, the assay demonstrated 100% specificity, 78% diagnostic accuracy, and 75% sensitivity compared with REBA HPV-ID test, and is much more rapid (15-40 min), less expensive (~ 3-4 USD/reaction) and does not require instrumentation (35-42 °C reaction condition so hand holding or tropical temperature is possible). Hence, the developed novel assay provides alternative screening tool for potential local screening. Furthermore, as this assay uses safe chemical reagents, it is safe for users., (© 2023. The Author(s).)
Published: 2023
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33. Six new cases of CRB2-related syndrome and a review of clinical findings in 28 reported patients.

Author: Adutwum M, Hurst A, Mirzaa G, Kushner JD, Rogers C, Khalek N, Cristancho AG, Burrill N, Seifert ME, Scarano MI, Schnur RE, and Slavotinek A
Subjects: Humans, Membrane Proteins genetics, Family, Carrier Proteins
Abstract: The Crumbs homolog-2 (CRB2)-related syndrome (CRBS-RS) is a rarely encountered condition initially described as a triad comprising ventriculomegaly, Finnish nephrosis, and elevated alpha-fetoprotein levels in maternal serum and amniotic fluid. CRB2-related syndrome is caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2-RS have highlighted renal disease with persistent proteinuria and steroid-resistant nephrotic syndrome (SRNS). We report six new and review 28 reported patients with pathogenic variants in CRB2. We compare clinical features and variant information in CRB2 in patients with CRB2-RS and in those with isolated renal disease. The kidneys were the most frequently involved body system and 11 patients had only renal manifestations with SRNS or nephrotic syndrome. Central nervous system involvement was the next most common manifestation, followed by cardiac findings that included Scimitar syndrome. There was a significant clustering of pathogenic variants for CRB2-RS in exons 8 and 10, whereas pathogenic variants in exons 12 and 13 were associated with isolated renal disease. Further information is needed to determine optimal management but monitoring for renal and ocular complications should be considered., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2023
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34. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Author: Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu CM, Hung YJ, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw E, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Vazquez-Moreno M, Feitosa MF, Wojczynski MK, Wang Z, Preuss MH, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Tsao NL, Verma A, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Frank M, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Bayyana S, Stringham HM, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Nardone GG, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Liang J, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Mercader JM, Costanzo MC, Jang D, Burtt NP, Villalpando CG, Orozco L, Fornage M, Tai E, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Qu J, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, Hart LM', Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Chuang LM, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, Willemsen AHM, Cupples L, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen Y, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson PWF, Frayling TM, Hirschhorn JN, Kathiresan S, Mohlke KL, Sun YV, Morris AP, Boehnke M, Brown CD, Natarajan P, Deloukas P, Willer CJ, Assimes TL, and Peloso GM
Subjects: Humans, Sex Characteristics, Phenotype, Lipids genetics, Polymorphism, Single Nucleotide, Genetic Pleiotropy, Genome-Wide Association Study, Genetic Predisposition to Disease
Abstract: Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery., Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism., Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk., (© 2022. The Author(s).)
Published: 2022
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35. Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Mali.

Author: Besançon S, Govender D, Sidibé AT, Noble JA, Togo A, Lane JA, Mack SJ, Atkinson MA, Wasserfall CH, Kakkat F, Martin GGN, and Ogle GD
Subjects: Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Male, Young Adult, Autoantibodies blood, Autoantibodies chemistry, C-Peptide blood, C-Peptide chemistry, Diabetes Mellitus, Type 2 genetics, Genetic Predisposition to Disease, Glutamate Decarboxylase, Mali epidemiology, Diabetes Mellitus, Type 1 genetics, HLA-DRB1 Chains genetics
Abstract: Objective: Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents., Research Design and Methods: The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases <21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology., Results: A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR = 0.27; p-value = 1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7 ng/ml (1.2 ± 0.9 nmol/L) in T1D cases at diagnosis., Conclusions: C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2022
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36. Dual Role of ACBD6 in the Acylation Remodeling of Lipids and Proteins.

Author: Soupene E and Kuypers FA
Subjects: Humans, 1-Acylglycerophosphocholine O-Acyltransferase metabolism, Acylation, Myristic Acid metabolism, ATP-Binding Cassette Transporters metabolism, Lipid Metabolism, Acetyl Coenzyme A metabolism, Protein Processing, Post-Translational
Abstract: The transfer of acyl chains to proteins and lipids from acyl-CoA donor molecules is achieved by the actions of diverse enzymes and proteins, including the acyl-CoA binding domain-containing protein ACBD6. N-myristoyl-transferase (NMT) enzymes catalyze the covalent attachment of a 14-carbon acyl chain from the relatively rare myristoyl-CoA to the N-terminal glycine residue of myr-proteins. The interaction of the ankyrin-repeat domain of ACBD6 with NMT produces an active enzymatic complex for the use of myristoyl-CoA protected from competitive inhibition by acyl donor competitors. The absence of the ACBD6/NMT complex in ACBD6.KO cells increased the sensitivity of the cells to competitors and significantly reduced myristoylation of proteins. Protein palmitoylation was not altered in those cells. The specific defect in myristoyl-transferase activity of the ACBD6.KO cells provided further evidence of the essential functional role of the interaction of ACBD6 with the NMT enzymes. Acyl-CoAs bound to the acyl-CoA binding domain of ACBD6 are acyl donors for the lysophospholipid acyl-transferase enzymes (LPLAT), which acylate single acyl-chain lipids, such as the bioactive molecules LPA and LPC. Whereas the formation of acyl-CoAs was not altered in ACBD6.KO cells, lipid acylation processes were significantly reduced. The defect in PC formation from LPC by the LPCAT enzymes resulted in reduced lipid droplets content. The diversity of the processes affected by ACBD6 highlight its dual function as a carrier and a regulator of acyl-CoA dependent reactions. The unique role of ACBD6 represents an essential common feature of (acyl-CoA)-dependent modification pathways controlling the lipid and protein composition of human cell membranes.
Published: 2022
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37. HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections.

Author: Loi E, Moi L, Cabras P, Arduino G, Costanzo G, Del Giacco S, Erlich HA, Firinu D, Caddori A, and Zavattari P
Subjects: Humans, HLA-C Antigens genetics, Immune Evasion, RNA, SARS-CoV-2, COVID-19
Abstract: One of the mechanisms by which viruses can evade the host's immune system is to modify the host's DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients' upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host's immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Loi, Moi, Cabras, Arduino, Costanzo, Del Giacco, Erlich, Firinu, Caddori and Zavattari.)
Published: 2022
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38. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

Author: Ramdas S, Judd J, Graham SE, Kanoni S, Wang Y, Surakka I, Wenz B, Clarke SL, Chesi A, Wells A, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Lee WJ, Hsiung CA, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Schönherr S, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Le P, Feitosa MF, Wojczynski MK, Hemerich D, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Noah TL, Verma A, Slieker RC, Lo KS, Zilhao NR, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Emmel C, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Sankareswaran A, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Morgan A, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, He KY, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Ida Chen YD, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Walker M, Scott LJ, Koistinen HA, Chandak GR, Mercader JM, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Lu F, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, T Hart LM, Elders PJM, Rader DJ, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney L, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, Willems van Dijk K, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Huey-Herng Sheu W, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ikram A, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Tuomilehto J, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen YE, Ho YL, Lynch JA, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Struan Grant, Natarajan P, Sun YV, Morris AP, Deloukas P, Peloso G, Assimes TL, Willer CJ, Zhu X, and Brown CD
Subjects: Chromatin genetics, Genomics, Humans, Lipids genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
Abstract: A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology., Competing Interests: Declaration of interests G.C.-P. is currently an employee of 23andMe Inc. M.J.C. is the Chief Scientist for Genomics England, a UK Government company. B.M. Psaty serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. G. Thorleifsson, A.H., D.F.G., H. Holm, U.T., and K.S. are employees of deCODE/Amgen Inc. V.S. has received honoraria for consultations from Novo Nordisk and Sanofi and has an ongoing research collaboration with Bayer Ltd. M. McCarthy has served on advisory panels for Pfizer, NovoNordisk, and Zoe Global and has received honoraria from Merck, Pfizer, Novo Nordisk, and Eli Lilly and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. M. McCarthy and A. Mahajan are employees of Genentech and holders of Roche stock. M.S. receives funding from Pfizer Inc. for a project unrelated to this work. M.E.K. is employed by SYNLAB MVZ Mannheim GmbH. W.M. has received grants from Siemens Healthineers, grants and personal fees from Aegerion Pharmaceuticals, grants and personal fees from AMGEN, grants from Astrazeneca, grants and personal fees from Sanofi, grants and personal fees from Alexion Pharmaceuticals, grants and personal fees from BASF, grants and personal fees from Abbott Diagnostics, grants and personal fees from Numares AG, grants and personal fees from Berlin-Chemie, grants and personal fees from Akzea Therapeutics, grants from Bayer Vital GmbH , grants from bestbion dx GmbH, grants from Boehringer Ingelheim Pharma GmbH Co KG, grants from Immundiagnostik GmbH, grants from Merck Chemicals GmbH, grants from MSD Sharp and Dohme GmbH, grants from Novartis Pharma GmbH, grants from Olink Proteomics, and other from Synlab Holding Deutschland GmbH, all outside the submitted work. A.V.K. has served as a consultant to Sanofi, Medicines Company, Maze Pharmaceuticals, Navitor Pharmaceuticals, Verve Therapeutics, Amgen, and Color Genomics; received speaking fees from Illumina and the Novartis Institute for Biomedical Research; received sponsored research agreements from the Novartis Institute for Biomedical Research and IBM Research, and reports a patent related to a genetic risk predictor (20190017119). S. Kathiresan is an employee of Verve Therapeutics and holds equity in Verve Therapeutics, Maze Therapeutics, Catabasis, and San Therapeutics. He is a member of the scientific advisory boards for Regeneron Genetics Center and Corvidia Therapeutics; he has served as a consultant for Acceleron, Eli Lilly, Novartis, Merck, Novo Nordisk, Novo Ventures, Ionis, Alnylam, Aegerion, Haug Partners, Noble Insights, Leerink Partners, Bayer Healthcare, Illumina, Color Genomics, MedGenome, Quest, and Medscape; and he reports patents related to a method of identifying and treating a person having a predisposition to or afflicted with cardiometabolic disease (20180010185) and a genetics risk predictor (20190017119). D.K. accepts consulting fees from Regeneron Pharmaceuticals. D.O.M.-K. is a part-time clinical research consultant for Metabolon, Inc. D. Saleheen has received support from the British Heart Foundation, Pfizer, Regeneron, Genentech, and Eli Lilly pharmaceuticals. P.N. reports investigator-initated grants from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis, personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Novartis, Roche / Genentech, is a co-founder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, geneXwell, and TenSixteen Bio, and spousal employment at Vertex, all unrelated to the present work. The spouse of C.J.W. is employed by Regeneron., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Published: 2022
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39. Author Correction: Comparative and demographic analysis of orang-utan genomes.

Author: Locke DP, Hillier LW, Warren WC, Worley KC, Nazareth LV, Muzny DM, Yang SP, Wang Z, Chinwalla AT, Minx P, Mitreva M, Cook L, Delehaunty KD, Fronick C, Schmidt H, Fulton LA, Fulton RS, Nelson JO, Magrini V, Pohl C, Graves TA, Markovic C, Cree A, Dinh HH, Hume J, Kovar CL, Fowler GR, Lunter G, Meader S, Heger A, Ponting CP, Marques-Bonet T, Alkan C, Chen L, Cheng Z, Kidd JM, Eichler EE, White S, Searle S, Vilella AJ, Chen Y, Flicek P, Ma J, Raney B, Suh B, Burhans R, Herrero J, Haussler D, Faria R, Fernando O, Darré F, Farré D, Gazave E, Oliva M, Navarro A, Roberto R, Capozzi O, Archidiacono N, Della Valle G, Purgato S, Rocchi M, Konkel MK, Walker JA, Ullmer B, Batzer MA, Smit AFA, Hubley R, Casola C, Schrider DR, Hahn MW, Quesada V, Puente XS, Ordoñez GR, López-Otín C, Vinar T, Brejova B, Ratan A, Harris RS, Miller W, Kosiol C, Lawson HA, Taliwal V, Martins AL, Siepel A, RoyChoudhury A, Ma X, Degenhardt J, Bustamante CD, Gutenkunst RN, Mailund T, Dutheil JY, Hobolth A, Schierup MH, Ryder OA, Yoshinaga Y, de Jong PJ, Weinstock GM, Rogers J, Mardis ER, Gibbs RA, and Wilson RK
Published: 2022
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40. Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL.

Author: Feng Q, Zhou M, Li S, Morimoto L, Hansen H, Myint SS, Wang R, Metayer C, Kang A, Fear AL, Pappas D, Erlich H, Hollenbach JA, Mancuso N, Trachtenberg E, de Smith AJ, Ma X, and Wiemels JL
Subjects: Case-Control Studies, Child, Cytokines, HLA Antigens, Humans, Immunoglobulins, Receptors, KIR genetics, Killer Cells, Natural, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
Abstract: Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions. We conducted a case-control study of 226 case child-mother pairs and 404 control child-mother pairs to evaluate the role of interaction between HLA genotypes in the offspring and maternal killer immunoglobulin-like receptor (KIR) genotypes in the etiology of childhood ALL, while considering potential mediation by neonatal cytokines and the immune-modulating enzyme arginase-II (ARG-II). We observed different associations between offspring HLA-maternal KIR activating profiles and the risk of ALL in different predicted genetic ancestry groups. For instance, in Latino subjects who experience the highest risk of childhood leukemia, activating profiles were significantly associated with a lower risk of childhood ALL (odds ratio [OR] = 0.59; 95% confidence interval [CI], 0.49-0.71) and a higher level of ARG-II at birth (coefficient = 0.13; 95% CI, 0.04-0.22). HLA-KIR activating profiles were also associated with a lower risk of ALL in non-Latino Asians (OR = 0.63; 95% CI, 0.38-1.01), although they had a lower tumor necrosis factor-α level (coefficient = -0.27; 95% CI, -0.49 to -0.06). Among non-Latino White subjects, no significant association was observed between offspring HLA-maternal KIR interaction and ALL risk or cytokine levels. The current study reports the association between offspring HLA-maternal KIR interaction and the development of childhood ALL with variation by predicted genetic ancestry. We also observed some associations between activating profiles and immune factors related to cytokine control; however, cytokines did not demonstrate causal mediation of the activating profiles on ALL risk., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Published: 2022
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41. Call for consensus in Chlamydia trachomatis nomenclature: moving from biovars, serovars, and serotypes to genovariants and genotypes.

Author: de Vries HJC, Pannekoek Y, Dean D, Bavoil PM, Borel N, Greub G, and Morré SA
Subjects: Consensus, Genotype, Humans, Serogroup, Chlamydia Infections diagnosis, Chlamydia Infections microbiology, Chlamydia trachomatis genetics
Published: 2022
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42. Comparison of Serum, Plasma, and Liver Zinc Measurements by AAS, ICP-OES, and ICP-MS in Diverse Laboratory Settings.

Author: Hall AG, King JC, and McDonald CM
Subjects: Liver, Mass Spectrometry methods, Spectrum Analysis, Laboratories, Zinc
Abstract: Progress improving zinc nutrition globally is slowed by limited understanding of population zinc status. This challenge is compounded when small differences in measurement can bias the determination of zinc deficiency rates. Our objective was to evaluate zinc analytical accuracy and precision among different instrument types and sample matrices using a standardized method. Participating laboratories analyzed zinc content of plasma, serum, liver samples, and controls, using a standardized method based on current practice. Instrument calibration and drift were evaluated using a zinc standard. Accuracy was evaluated by percent error vs. reference, and precision by coefficient of variation (CV). Seven laboratories in 4 countries running 9 instruments completed the exercise: 4 atomic absorbance spectrometers (AAS), 1 inductively coupled plasma optical emission spectrometer (ICP-OES), and 4 ICP mass spectrometers (ICP-MS). Calibration differed between individual instruments up to 18.9% (p < 0.001). Geometric mean (95% CI) percent error was 3.5% (2.3%, 5.2%) and CV was 2.1% (1.7%, 2.5%) overall. There were no significant differences in percent error or CV among instrument types (p = 0.91, p = 0.15, respectively). Among sample matrices, serum and plasma zinc measures had the highest CV: 4.8% (3.0%, 7.7%) and 3.9% (2.9%, 5.4%), respectively (p < 0.05). When using standardized materials and methods, similar zinc concentration values, accuracy, and precision were achieved using AAS, ICP-OES, or ICP-MS. However, method development is needed for improvement in serum and plasma zinc measurement precision. Differences in calibration among instruments demonstrate a need for harmonization among laboratories., (© 2021. The Author(s).)
Published: 2022
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43. High-level correction of the sickle mutation is amplified in vivo during erythroid differentiation.

Author: Magis W, DeWitt MA, Wyman SK, Vu JT, Heo SJ, Shao SJ, Hennig F, Romero ZG, Campo-Fernandez B, Said S, McNeill MS, Rettig GR, Sun Y, Wang Y, Behlke MA, Kohn DB, Boffelli D, Walters MC, Corn JE, and Martin DIK
Abstract: Background: A point mutation in sickle cell disease (SCD) alters one amino acid in the β-globin subunit of hemoglobin, with resultant anemia and multiorgan damage that typically shortens lifespan by decades. Because SCD is caused by a single mutation, and hematopoietic stem cells (HSCs) can be harvested, manipulated, and returned to an individual, it is an attractive target for gene correction., Results: An optimized Cas9 ribonucleoprotein (RNP) with an ssDNA oligonucleotide donor together generated correction of at least one β-globin allele in more than 30% of long-term engrafting human HSCs. After adopting a high-fidelity Cas9 variant, efficient correction with minimal off-target events also was observed. In vivo erythroid differentiation markedly enriches for corrected β-globin alleles, indicating that erythroblasts carrying one or more corrected alleles have a survival advantage., Significance: These findings indicate that the sickle mutation can be corrected in autologous HSCs with an optimized protocol suitable for clinical translation., Competing Interests: The authors have no conflicts of interest. MCW is medical director of All Cells, Inc., from which some of the human CD34+ cells for the studies were purchased. Matthew S.McNeill, Garrett R. Rettig, Yongming Sun, Yu Wang, and Mark A. Behlke are employees of IDT, Inc. Mark A. De-Witt is a consultant for Synthego Inc. and CellFE Inc. Synthego Inc. did not contribute to this work. MCW is medical director of All Cells, Inc., from which some of the human CD34+ cells for the studies were purchased. Matthew S.McNeill, Garrett R. Rettig, Yongming Sun, Yu Wang, and Mark A. Behlke are employees of IDT, Inc. Mark A. De-Witt is a consultant for Synthego Inc. and CellFE Inc. Synthego Inc. did not contribute to this work. GRR is an employee of Integrated DNA Technologies and Danaher Corp and shareholder of Danaher Corp A single patent application was filed from this project: USPAT APPLICATION NUMBER: 17047025 - Methods for Treating Sickle Cell Disease. Products and tools supplied by IDT are for research use only and not intended for diagnostic or therapeutic purposes. Purchaser and/or user is solely responsible for all decisions regarding the use of these products and any associated regulatory or legal obligations., (© 2022.)
Published: 2022
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44. Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

Author: Islam MM, Black RE, Krebs NF, Westcott J, Long J, Islam KM, Peerson JM, Sthity RA, Khandaker AM, Hasan M, El Arifeen S, Ahmed T, King JC, and McDonald CM
Subjects: Bangladesh epidemiology, Child, Child, Preschool, Diarrhea epidemiology, Diarrhea prevention & control, Dietary Supplements, Double-Blind Method, Humans, Infant, Iron, Micronutrients, Powders, Tablets, Trace Elements therapeutic use, Zinc
Abstract: Background: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences., Objectives: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children., Methods: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA., Results: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05)., Conclusions: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)
Published: 2022
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45. Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity.

Author: Olson E, Suh JH, Schwarz JM, Noworolski SM, Jones GM, Barber JR, Erkin-Cakmak A, Mulligan K, Lustig RH, and Mietus-Snyder M
Subjects: Biomarkers metabolism, Cardiometabolic Risk Factors, Child, Humans, Insulin Resistance physiology, Lipogenesis, Liver metabolism, Ceramides metabolism, Fructose administration & dosage, Pediatric Obesity
Abstract: Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (-0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.
Published: 2022
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46. Marginal Zinc Deficiency Alters Essential Fatty Acid Metabolism in Healthy Men.

Author: Suh JH, Zyba SJ, Shigenaga M, McDonald CM, and King JC
Subjects: Cholesterol, HDL, Cholesterol, LDL, Fatty Acid Desaturases, Humans, Lipid Metabolism, Male, Triglycerides, Zinc, Fatty Acids, Essential, Phytic Acid
Abstract: Background: Rice biofortification with Zinc (Zn) can improve the Zn status of rice-consuming populations. However, the metabolic impact in humans consuming Zn-biofortified rice is unknown., Objectives: To determine the effects of Zn-biofortified rice on lipid metabolism in normolipidemic men., Methods: The men consumed a rice-based diet containing 6 mg Zn/d and 1.5 g phytate (phytate/Zn ratio = 44) for 2 wk followed by a 10-mg Zn/d diet without phytate for 4 wk. An ad libitum diet supplemented with 25 mg Zn/d was then fed for 3 wk. Fasting blood samples were taken at baseline and at the end of each metabolic period for measuring plasma zinc, glucose, insulin, triglyceride (TG), LDL and HDL cholesterol, fatty acids, oxylipins, and fatty acid desaturase activities. Statistical differences were assessed by linear mixed model., Results: Fatty acid desaturase (FADS) 1 activity decreased by 29.1% (P = 0.007) when the 6-mg Zn/d diet was consumed for 2 wk. This change was associated with significant decreases in HDL and LDL cholesterol. The alterations in FADS1, HDL cholesterol, and TG remained unchanged when Zn intakes were increased to 10 mg/d for 4 wk. Supplementation with 25 mg Zn/d for 3 wk normalized these metabolic changes and significantly increased LDL cholesterol at the end of this metabolic period compared with baseline. FADS1 activity was inversely correlated with FADS2 (rmcorr = -0.52; P = 0.001) and TG (rmcorr = -0.55; P = 0.001) at all time points., Conclusions: A low-zinc, high-phytate rice-based diet reduced plasma HDL cholesterol concentrations and altered fatty acid profiles in healthy men within 2 wk. Consuming 10 mg Zn/d without phytate for 4 wk did not improve the lipid profiles, but a 25-mg Zn/d supplement corrects these alterations in lipid metabolism within 3 wk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
Published: 2022
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47. Noninvasive Prenatal Test for β-Thalassemia and Sickle Cell Disease Using Probe Capture Enrichment and Next-Generation Sequencing of DNA in Maternal Plasma.

Author: Erlich HA, López-Peña C, Carlberg KT, Shih S, Bali G, Yamaguchi KD, Salamon H, Das R, Lal A, and Calloway CD
Subjects: DNA analysis, DNA genetics, Female, High-Throughput Nucleotide Sequencing, Humans, Pregnancy, Anemia, Sickle Cell diagnosis, Anemia, Sickle Cell genetics, Hemoglobinopathies, beta-Thalassemia diagnosis, beta-Thalassemia genetics
Abstract: Background: Noninvasive prenatal testing (NIPT) of chromosomal aneuploidies based on next-generation sequencing (NGS) analysis of fetal DNA in maternal plasma is well established, but testing for autosomal recessive disorders remains challenging. NGS libraries prepared by probe capture facilitate the analysis of the short DNA fragments plasma. This system has been applied to the β-hemoglobinopathies to reduce the risk to the fetus., Method: Our probe panel captures >4 kb of the HBB region and 435 single-nucleotide polymorphisms (SNPs) used to estimate fetal fraction. Contrived mixtures of DNA samples, plasma, and whole blood samples from 7 pregnant women with β-thalassemia or sickle cell anemia mutations and samples from the father, sibling, and baby or chorionic villus were analyzed. The fetal genotypes, including point mutations and deletions, were inferred by comparing the observed and expected plasma sequence read ratios, based on fetal fraction, at the mutation site and linked SNPs. Accuracy was increased by removing PCR duplicates and by in silico size selection of plasma sequence reads. A probability was assigned to each of the potential fetal genotypes using a statistical model for the experimental variation, and thresholds were established for assigning clinical status., Results: Using in silico size selection of plasma sequence files, the predicted clinical fetal genotype assignments were correct in 9 of 10 plasma libraries with maternal point mutations, with 1 inconclusive result. For 2 additional plasmas with deletions, the most probable fetal genotype was correct. The β-globin haplotype determined from linked SNPs, when available, was used to infer the fetal genotype at the mutation site., Conclusion: This probe capture NGS assay demonstrates the potential of NIPT for β-hemoglobinopathies., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2022
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48. Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells.

Author: Song W, Beigneux AP, Winther AL, Kristensen KK, Grønnemose AL, Yang Y, Tu Y, Munguia P, Morales J, Jung H, de Jong PJ, Jung CJ, Miyashita K, Kimura T, Nakajima K, Murakami M, Birrane G, Jiang H, Tontonoz P, Ploug M, Fong LG, and Young SG
Subjects: Animals, Capillaries metabolism, Endothelial Cells metabolism, Mice, Static Electricity, Lipoprotein Lipase genetics, Lipoprotein Lipase metabolism, Receptors, Lipoprotein chemistry, Receptors, Lipoprotein genetics, Receptors, Lipoprotein metabolism
Abstract: GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.
Published: 2022
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49. Biofortified Wheat Increases Dietary Zinc Intake: A Randomised Controlled Efficacy Study of Zincol-2016 in Rural Pakistan.

Author: Lowe NM, Zaman M, Khan MJ, Brazier AKM, Shahzad B, Ullah U, Khobana G, Ohly H, Broadley MR, Zia MH, McArdle HJ, Joy EJM, Bailey EH, Young SD, Suh J, King JC, Sinclair J, and Tishkovskaya S
Abstract: A new variety of zinc biofortified wheat (Zincol-2016) was released in Pakistan in 2016. The primary aim of this study was to examine the effects of consuming Zincol-2016 wheat flour on biochemical and functional markers of zinc status in a population with widespread zinc deficiency. An individually-randomised, double-blind, placebo-controlled cross over design was used. Fifty households were recruited to participate in the study, with each household included at least one woman of reproductive age (16-49 years) who was neither pregnant nor breast feeding or currently taking nutritional supplements. All households were provided with control flour for an initial 2-week baseline period, followed by the intervention period where households were randomly allocated in a 1:1 ratio to receive biofortified flour (group A; n = 25) and control flour (group B; n = 25) for 8-weeks, then switched to the alternate flour for 8-weeks. The trial has been registered with the ISRCTN (https://www.isrctn.com), ID ISRCTN83678069. The primary outcome measure was plasma zinc concentration, and the secondary outcome measures were plasma selenium and copper concentrations, plasma copper:zinc ratio and fatty acid desaturase and elongase activity indices. Nutrient intake was assessed using 24-h dietary recall interviews. Mineral concentrations in plasma were measured using inductively coupled plasma mass spectrometry and free fatty acids and sphingolipids by mass spectrometry. Linear Mixed Model regression and General Linear Model with repeated measures were used to analyse the outcomes. Based on an average flour consumption of 224 g/day, Zincol-2016 flour provided an additional daily zinc intake of between 3.0 and 6.0 mg for white and whole grain flour, respectively. No serious adverse events were reported. This resulted in significant, increase in plasma zinc concentration after 4 weeks [mean difference 41.5 μg/L, 95% CI (6.9-76.1), p = 0.02]. This was not present after 8 weeks ( p = 0.6). There were no consistent significant effects of the intervention on fatty acid desaturase and elongase activity indices. Regular consumption of Zincol-2016 flour increased the daily zinc intake of women of reproductive age by 30-60%, however this was not associated with a sustained improvement in indices of zinc status., Competing Interests: MHZ is employed by Fauji Fertilizer Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lowe, Zaman, Khan, Brazier, Shahzad, Ullah, Khobana, Ohly, Broadley, Zia, McArdle, Joy, Bailey, Young, Suh, King, Sinclair and Tishkovskaya.)
Published: 2022
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50. Nutrition in Thalassemia: A Systematic Review of Deficiency, Relations to Morbidity, and Supplementation Recommendations.

Author: Goldberg EK, Lal A, and Fung EB
Subjects: Humans, Practice Guidelines as Topic, Dietary Supplements, Nutritional Status, Nutritional Support, Thalassemia therapy, Vitamins therapeutic use
Abstract: Background: Reports of nutritional deficiencies in patients with thalassemia (Thal) are common. Despite its importance, however, nutritionally focused research in Thal has been limited by inadequate sample size, inconsistent methodology, a lack of control comparisons, and few interventional trials. Due to these limitations, clinicians lack evidence-based nutrition recommendations to support clinical decision-making. This systematic review summarizes observed relationships between nutrition and morbidity in Thal published in the last 3 decades., Methods: PubMed, Web of Science, and Embase were screened for articles pertaining to nutrition in Thal using comprehensive search terms. Studies performed in humans, written in English, and published between 1990 and 2020 were included. Over 2100 manuscripts were identified, from which 97 were included., Results: Patients with Thal were most often deficient in vitamins A, C, D, selenium, and zinc. Prevalence of nutritional deficiency was positively correlated with age and iron overload. Evidence to support the role of vitamin D and zinc for bone health was observed; zinc was also found to improve glucose metabolism., Conclusions: Due to the risk for multinutrient deficiency, nutritional status should be assessed annually in patients with Thal with prompt nutrient replacement when deficiency is detected. Routine supplementation with vitamin D and zinc is recommended., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2022
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