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3,304 results on '"Wellcome Trust Genome Campus"'

1. Cyrface - Bridging Cytoscape with R

Author: Emanuel Gonçalves The European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom and Julio Saez-Rodriguez The European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom
Abstract: Cyrface establishes an interface between R and Cytoscape by using different Java-R libraries, e.g. Rserve, RCaller. Cyrface can be used as a Cytoscape plug-in, e.g. to run R commands within Cytoscape, or used as a library to allow your plug-in to connect to R.
Published: 2013
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2. Systematic comparison of the human saliva and plasma proteomes

Author: Departments of Medicine and Genetics and Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA, EMBL Outstation, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK, Calibrant Biosystems, Gaithersburg, MD, USA, Biomarkers and Systems Biology Center, Research Triangle Institute, Research Triangle, NC, USA, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA, Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA, College of Dentistry, New York University, New York, NY, USA, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, CA, USA, Department of Oral Medicine, Diagnosis, and Radiology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA, Scripps Research Institute, La Jolla, CA, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA ; Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA ; Additional corresponding author, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA ; University of California-Los Angeles, School of Dentistry, 73-017 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA Fax: +1-310-825-7609, Yan, Weihong, Apweiler, Rolf, Balgley, Brian M., Boontheung, Pinmanee, Bundy, Jonathan L., Cargile, Benjamin J., Cole, Steve, Fang, Xueping, Gonzalez-Begne, Mireya, Griffin, Timothy J., Hagen, Fred, Hu, Shen, Wolinsky, Lawrence E., Lee, Cheng S., Malamud, Daniel, Melvin, James E., Menon, Rajasree, Mueller, Michael, Qiao, Renli, Rhodus, Nelson L., Sevinsky, Joel R., States, David, Stephenson, James L., Than, Shawn, Yates, John R., Yu, Weixia, Xie, Hongwei, Xie, Yongming, Omenn, Gilbert S., Loo, Joseph A., Wong, David T., Departments of Medicine and Genetics and Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA, EMBL Outstation, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK, Calibrant Biosystems, Gaithersburg, MD, USA, Biomarkers and Systems Biology Center, Research Triangle Institute, Research Triangle, NC, USA, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA, Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA, Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA, College of Dentistry, New York University, New York, NY, USA, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, CA, USA, Department of Oral Medicine, Diagnosis, and Radiology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA, Scripps Research Institute, La Jolla, CA, USA, Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, USA ; Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA ; Additional corresponding author, UCLA School of Dentistry and UCLA Dental Research Institute, University of California-Los Angeles, Los Angeles, CA, USA ; University of California-Los Angeles, School of Dentistry, 73-017 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA Fax: +1-310-825-7609, Yan, Weihong, Apweiler, Rolf, Balgley, Brian M., Boontheung, Pinmanee, Bundy, Jonathan L., Cargile, Benjamin J., Cole, Steve, Fang, Xueping, Gonzalez-Begne, Mireya, Griffin, Timothy J., Hagen, Fred, Hu, Shen, Wolinsky, Lawrence E., Lee, Cheng S., Malamud, Daniel, Melvin, James E., Menon, Rajasree, Mueller, Michael, Qiao, Renli, Rhodus, Nelson L., Sevinsky, Joel R., States, David, Stephenson, James L., Than, Shawn, Yates, John R., Yu, Weixia, Xie, Hongwei, Xie, Yongming, Omenn, Gilbert S., Loo, Joseph A., and Wong, David T.
Abstract: The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides. To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released. A total of 1939 nonredundant salivary proteins were compiled from a total of 19 14474 unique peptide sequences identified from whole and ductal salivas[semi] 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma. The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics.
Published: 2009

3. Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Author: Campbell, Peter [Wellcome Trust Genome Campus, Cambridgeshire (United Kingdom); Univ. of Cambridge, Cambridge (United Kingdom)]
Published: 2017
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4. Corrigendum: The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons

Author: Braasch, Ingo, Gehrke, Andrew R., Smith, Jeramiah J., Kawasaki, Kazuhiko, Manousaki, Tereza, Pasquier, Jérémy, Amores, Angel, Desvignes, Thomas, Batzel, Peter, Catchen, Julian, Berlin, Aaron M., Campbell, Michael S., Barrell, Daniel, Martin, Kyle J., Mulley, John F., Ravi, Vydianathan, Lee, Alison P., Nakamura, Tetsuya, Chalopin, Domitille, Fan, Shaohua, Wcisel, Dustin, Cañestro, Cristian, Sydes, Jason, Beaudry, Felix E.G., Sun, Yi, Hertel, Jana, Beam, Michael J., Fasold, Mario, Ishiyama, Mikio, Johnson, Jeremy, Kehr, Steffi, Lara, Marcia, Letaw, John H., Litman, Gary W., Litman, Ronda T., Mikami, Masato, Ota, Tatsuya, Saha, Nil Ratan, Williams, Louise, Stadler, Peter F., Wang, Han, Taylor, John S., Fontenot, Quenton, Ferrara, Allyse, Searle, Stephen M.J., Aken, Bronwen, Yandell, Mark, Schneider, Igor, Yoder, Jeffrey A, Volff, Jean-Nicolas, Meyer, Axel, Amemiya, Chris T, Venkatesh, Byrappa, Holland, Peter W.H., Guiguen, Yann, Bobe, Julien, Shubin, Neil H., Di Palma, Federica, Alföldi, Jessica, Lindblad-Toh, Kerstin, Postlethwait, John H., Institute of Neuroscience, National Research Council [Italy] (CNR), Department of Integrative Biology [Berkeley] (IB), University of California [Berkeley], University of California-University of California, Department of Organismal Biology and Anatomy, University of Chicago, Department of Biology, Northern Arizona University [Flagstaff], Department of Anthropology, University of California, Pennsylvania State University (Penn State), Penn State System, Hellenic Centre for Marine Research, Hellenic Center for Marine Research (HCMR), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Animal Biology, University of Pennsylvania [Philadelphia], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Eccles Institute of Human Genetics, University of Utah, Cold Spring Harbor, Cold Spring Harbor Laboratory, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Department of Zoology, Auburn University (AU), Department of Animal and Plant Sciences [Sheffield], University of Sheffield [Sheffield], School of Biological Sciences [Bangor], Bangor University, Comparative Genomics Laboratory, Agency for Science, Technology and Research (A*STAR), International Institute of Molecular and Cell Biology, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, The University of Texas M.D. Anderson Cancer Center [Houston], Department of Molecular Biomedical Sciences Raleigh, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Center for Comparative Medicine and Translational Research Raleigh, Departament de Genètica, Universitat Autònoma de Barcelona [Barcelona] (UAB), Institut de Recerca de la Biodiversitat, University of Barcelona, University of Victoria, Center for Circadian Clocks, Soochow University, School of Biology and Basic Medical Sciences, Medical College, Bioinformatics Group, Department of Computer Science, Universität Leipzig [Leipzig], Young Investigators Group Bioinformatics and Transcriptomics, Department of Proteomics, Helmholtz Centre for Environmental Research (UFZ), Department of Dental Hygiene, Nippon Dental University, Morsani College of Medicine, Department of Pediatrics, University of South Florida (USF), Department of Microbiology, Department of Evolutionary Studies of Biosystems, SOKENDAI, Graduate University for Advanced Studies, Molecular Genetics Program, Benaroya Research Institute, Department of Biological Sciences, The Open University [Milton Keynes] (OU), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, European Bioinformatics Institute, Instituto de Ciências Biológicas, Federal University of Para - Universidade Federal do Para [Belem - Brésil], Department of Molecular Biomedical Sciences, University of North Carolina System (UNC)-University of North Carolina System (UNC)-College of Veterinary Medicine Raleigh, Center for Comparative Medicine and Translational Research, International Max Planck Research School for Organismal Biology (IMPRS), University of Konstanz, Genome Analysis Center, Vertebrate and Health Genomics, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Hellenic Centre for Marine Research (HCMR), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Universitat Autònoma de Barcelona (UAB), University of Victoria [Canada] (UVIC), Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), University of South Florida [Tampa] (USF), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), University of California (UC), University of Pennsylvania, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Universität Leipzig, and Federal University of Para - Universidade Federal do Pará - UFPA [Belém, Brazil] (UFPA)
Subjects: [SDV]Life Sciences [q-bio], analyse phylogénétique, reproduction, poisson, analyse génomique, human, chromosome, analyse du transcriptome, genome, duplication des génomes, miRNA, fish, teleost, physiologie animale, séquence régulatrice, vertébré, homme, lepisosteus oculatus, interaction animal homme, lépisosté tacheté, évolution du génome, fonction des gènes, teleosteen, regulatory sequence, vertebrates, immunité, expression des gènes
Abstract: The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons (vol 48, pg 427, 2016); As we intended, other researchers have been able to use the draft spotted gar genome sequence available from the Broad Institute website since December 2011, the assembly LepOcu1 publicly available from NCBI since 13 January 2012 under accession code GCA000242695.1, and the Ensembl gene annotation (version 74, December 2013; http://www.ensembl.org/Lepisosteus_oculatus/Info/Annotation) and recent annotation by NCBI on 15 May 2014 guided by RNA sequence data from ten tissues. While this article was in review, a paper (Nature 526, 108–111, 2015) was published that arrives at conclusions similar to some of our own analyses, and we wish to acknowledge that publication, which used our unpublished data and genome annotations, emphasizing the importance of the strategy of early release of sequence data. The correction has been made to the HTML and PDF versions of the article.
Published: 2016

5. Structural and functional annotation of the porcine immunome

Author: Toby Hunt, James G. R. Gilbert, Denise Carvalho-Silva, Ting Hua Huang, Shu Hong Zhao, Alan Archibald, Tahar Ait-Ali, John C. Schwartz, Christopher K. Tuggle, Elisabetta Giuffra, Frank Blecha, M. Kay, Celine Chen, Zhi-Liang Hu, Ranjit S. Kataria, Hirohide Uenishi, Claire Rogel-Gaillard, Matthew Hardy, Catherine E. Snow, Tom C. Freeman, Sara Botti, Michael P. Murtaugh, Géraldine Pascal, Katherine M. Mann, Mark G. Thomas, Bertrand Bed'Hom, Joan K. Lunney, Yongming Sang, Megan Bystrom, Jie Zhang, Jane E. Loveland, Clara Amid, Ryan Pei Yen Cheng, James M. Reecy, Harry D. Dawson, Matthew Astley, Anna Anselmo, Daisuke Toki, Dario Beraldi, Charles A. Steward, Eric Fritz, Jennifer Harrow, Hiroki Shinkai, David A. Hume, Ronan Kapetanovic, Bouabid Badaoui, Daniel Berman, Takeya Morozumi, Laurens G. Wilming, David Lloyd, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, USDA-ARS : Agricultural Research Service, Informatics Departmentt, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ARS BA Animal Parasitic Diseases Laboratory, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Laboratory of Animal Genetics, Breeding, and Reproduction, Huazhong Agricultural University, Informatics Department, Wellcome Trust Genome Campus, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Department of Animal Science, Iowa State University (ISU), Integrative Biology Unit, Parco Tecnologico Padano, BA Animal Parasitic Diseases Laboratory, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Department of Veterinary and Biomedical Sciences, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), AgroParisTech-Institut National de la Recherche Agronomique (INRA), United States Department of Agriculture - Agricultural Research Service, Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), University of Minnesota [Twin Cities], Rogel Gaillard, Claire, and Tuggle, Christopher K
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Models, Molecular, INTEGRATED MAP, Porcine, Protein Conformation, Swine, Genome, Mice, 0302 clinical medicine, Receptors, KIR, Gene Duplication, INFECTION, Gene cluster, SWINE, évolution, GENE-EXPRESSION, BIOMEDICAL MODEL, Genetics, Co-expression network, 0303 health sciences, Phylogenetic analysis, GENOME SEQUENCE, Genomics, Genome project, Molecular Sequence Annotation, Accelerated evolution, DNA microarray, Research Article, Biotechnology, réponse immunitaire, Receptors, Antigen, T-Cell, Immunoglobulins, Locus (genetics), Biology, analyse phylogénétique, Evolution, Molecular, analyse de génome, 03 medical and health sciences, Species Specificity, LOCUS, Animals, Humans, porcin, Immune response, Selection, Genetic, Gene, 030304 developmental biology, immune response, porcine, genome annotation, co-expression network, phylogenetic analysis, accelerated evolution, Immunity, EVOLUTION, PIG GENOME, ANTIBODY REPERTOIRE DEVELOPMENT, Cattle, 030217 neurology & neurosurgery, Genome annotation
Abstract: Background The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems. Results The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome. Conclusions This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.
Published: 2013

6. Phylogenetic distribution and evolutionary dynamics of nod and T3SS genes in the genus Bradyrhizobium

Author: Teulet, Albin, Gully, Djamel, Rouy, Zoe, Camuel, Alicia, Koebnik, Ralf, Giraud, Eric, Lassalle, Florent, Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Analyse Bio-Informatique pour la Génomique et le Métabolisme (LABGeM), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), UMR - Interactions Plantes Microorganismes Environnement (UMR IPME), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud]), Imperial College London, Wellcome Trust Genome Campus, French Ministry of National Education, Higher Education and Research, Medical Research Council UK (MRC) MR/N010760/1, ANR-16-CE20-0013,SymEffectors,Système de sécrétion de type 3 pour la symbiose fixatrice d'azote(2016), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)-Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), and Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Genomics, legume, biochemical phenomena, metabolism, and nutrition, symbiosis, type III secretion system, Evolution, Molecular, rhizobium, effector, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Bacterial Proteins, Multigene Family, Type III Secretion Systems, bacteria, nodulation, Bradyrhizobium, Microbe-Niche Interactions: Mutualism, commensalism and parasitism, Phylogeny, Research Article, Peptide Hydrolases
Abstract: International audience; Bradyrhizobium are abundant soil bacteria and the major symbiont of legumes. The recent availability of Bradyrhizobium genome sequences provides a large source of information for analysis of symbiotic traits. In this study, we investigated the evolutionary dynamics of the nodulation genes (nod) and their relationship with the genes encoding type III secretion systems (T3SS) and their effectors among bradyrhizobia. Based on the comparative analysis of 146 Bradyrhizobium genome sequences, we identified six different types of T3SS gene clusters. The two predominant cluster types are designated RhcIa and RhcIb and both belong to the RhcI-T3SS family previously described in other rhizobia. They are found in 92/146 strains, most of them also containing nod genes. RhcIa and RhcIb gene clusters differ in the genes they carry: while the translocon-encoding gene nopX is systematically found in strains containing RhcIb, the nopE and nopH genes are specifically conserved in strains containing RhcIa, suggesting that these last two genes might functionally substitute nopX and play a role related to effector translocation. Phylogenetic analysis suggests that bradyrhizobia simultaneously gained nod and RhcI-T3SS gene clusters via horizontal transfer or subsequent vertical inheritance of a symbiotic island containing both. Sequence similarity searches for known Nop effector proteins in bradyrhizobial proteomes revealed the absence of a so-called core effectome, i.e. that no effector is conserved among all Bradyrhizobium strains. However, NopM and SUMO proteases were found to be the main effector families, being represented in the majority of the genus. This study indicates that bradyrhizobial T3SSs might play a more significant symbiotic role than previously thought and provides new candidates among T3SS structural proteins and effectors for future functional investigations.
Published: 2020

7. Protein–DNA Interactions: The Story so Far and a New Method for Prediction

Author: Thornton, Janet [EMBL –European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK]
Published: 2003
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8. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Author: Anne H. O’Donnell-Luria, Lynn S. Pais, Víctor Faundes, Jordan C. Wood, Abigail Sveden, Victor Luria, Rami Abou Jamra, Andrea Accogli, Kimberly Amburgey, Britt Marie Anderlid, Silvia Azzarello-Burri, Alice A. Basinger, Claudia Bianchini, Lynne M. Bird, Rebecca Buchert, Wilfrid Carre, Sophia Ceulemans, Perrine Charles, Helen Cox, Lisa Culliton, Aurora Currò, Florence Demurger, James J. Dowling, Benedicte Duban-Bedu, Christèle Dubourg, Saga Elise Eiset, Luis F. Escobar, Alessandra Ferrarini, Tobias B. Haack, Mona Hashim, Solveig Heide, Katherine L. Helbig, Ingo Helbig, Raul Heredia, Delphine Héron, Bertrand Isidor, Amy R. Jonasson, Pascal Joset, Boris Keren, Fernando Kok, Hester Y. Kroes, Alinoë Lavillaureix, Xin Lu, Saskia M. Maas, Gustavo H.B. Maegawa, Carlo L.M. Marcelis, Paul R. Mark, Marcelo R. Masruha, Heather M. McLaughlin, Kirsty McWalter, Esther U. Melchinger, Saadet Mercimek-Andrews, Caroline Nava, Manuela Pendziwiat, Richard Person, Gian Paolo Ramelli, Luiza L.P. Ramos, Anita Rauch, Caitlin Reavey, Alessandra Renieri, Angelika Rieß, Amarilis Sanchez-Valle, Shifteh Sattar, Carol Saunders, Niklas Schwarz, Thomas Smol, Myriam Srour, Katharina Steindl, Steffen Syrbe, Jenny C. Taylor, Aida Telegrafi, Isabelle Thiffault, Doris A. Trauner, Helio van der Linden, Silvana van Koningsbruggen, Laurent Villard, Ida Vogel, Julie Vogt, Yvonne G. Weber, Ingrid M. Wentzensen, Elysa Widjaja, Jaroslav Zak, Samantha Baxter, Siddharth Banka, Lance H. Rodan, Jeremy F. McRae, Stephen Clayton, Tomas W. Fitzgerald, Joanna Kaplanis, Elena Prigmore, Diana Rajan, Alejandro Sifrim, Stuart Aitken, Nadia Akawi, Mohsan Alvi, Kirsty Ambridge, Daniel M. Barrett, Tanya Bayzetinova, Philip Jones, Wendy D. Jones, Daniel King, Netravathi Krishnappa, Laura E. Mason, Tarjinder Singh, Adrian R. Tivey, Munaza Ahmed, Uruj Anjum, Hayley Archer, Ruth Armstrong, Jana Awada, Meena Balasubramanian, Diana Baralle, Angela Barnicoat, Paul Batstone, David Baty, Chris Bennett, Jonathan Berg, Birgitta Bernhard, A. Paul Bevan, Maria Bitner-Glindzicz, Edward Blair, Moira Blyth, David Bohanna, Louise Bourdon, David Bourn, Lisa Bradley, Angela Brady, Simon Brent, Carole Brewer, Kate Brunstrom, David J. Bunyan, John Burn, Natalie Canham, Bruce Castle, Kate Chandler, Elena Chatzimichali, Deirdre Cilliers, Angus Clarke, Susan Clasper, Jill Clayton-Smith, Virginia Clowes, Andrea Coates, Trevor Cole, Irina Colgiu, Amanda Collins, Morag N. Collinson, Fiona Connell, Nicola Cooper, Lara Cresswell, Gareth Cross, Yanick Crow, Mariella D’Alessandro, Tabib Dabir, Rosemarie Davidson, Sally Davies, Dylan de Vries, John Dean, Charu Deshpande, Gemma Devlin, Abhijit Dixit, Angus Dobbie, Alan Donaldson, Dian Donnai, Deirdre Donnelly, Carina Donnelly, Angela Douglas, Sofia Douzgou, Alexis Duncan, Jacqueline Eason, Sian Ellard, Ian Ellis, Frances Elmslie, Karenza Evans, Sarah Everest, Tina Fendick, Richard Fisher, Frances Flinter, Nicola Foulds, Andrew Fry, Alan Fryer, Carol Gardiner, Lorraine Gaunt, Neeti Ghali, Richard Gibbons, Harinder Gill, Judith Goodship, David Goudie, Emma Gray, Andrew Green, Philip Greene, Lynn Greenhalgh, Susan Gribble, Rachel Harrison, Lucy Harrison, Victoria Harrison, Rose Hawkins, Liu He, Stephen Hellens, Alex Henderson, Sarah Hewitt, Lucy Hildyard, Emma Hobson, Simon Holden, Muriel Holder, Susan Holder, Georgina Hollingsworth, Tessa Homfray, Mervyn Humphreys, Jane Hurst, Ben Hutton, Stuart Ingram, Melita Irving, Lily Islam, Andrew Jackson, Joanna Jarvis, Lucy Jenkins, Diana Johnson, Elizabeth Jones, Dragana Josifova, Shelagh Joss, Beckie Kaemba, Sandra Kazembe, Rosemary Kelsell, Bronwyn Kerr, Helen Kingston, Usha Kini, Esther Kinning, Gail Kirby, Claire Kirk, Emma Kivuva, Alison Kraus, Dhavendra Kumar, V. K. Ajith Kumar, Katherine Lachlan, Wayne Lam, Anne Lampe, Caroline Langman, Melissa Lees, Derek Lim, Cheryl Longman, Gordon Lowther, Sally A. Lynch, Alex Magee, Eddy Maher, Alison Male, Sahar Mansour, Karen Marks, Katherine Martin, Una Maye, Emma McCann, Vivienne McConnell, Meriel McEntagart, Ruth McGowan, Kirsten McKay, Shane McKee, Dominic J. McMullan, Susan McNerlan, Catherine McWilliam, Sarju Mehta, Kay Metcalfe, Anna Middleton, Zosia Miedzybrodzka, Emma Miles, Shehla Mohammed, Tara Montgomery, David Moore, Sian Morgan, Jenny Morton, Hood Mugalaasi, Victoria Murday, Helen Murphy, Swati Naik, Andrea Nemeth, Louise Nevitt, Ruth Newbury-Ecob, Andrew Norman, Rosie O’Shea, Caroline Ogilvie, Kai-Ren Ong, Soo-Mi Park, Michael J. Parker, Chirag Patel, Joan Paterson, Stewart Payne, Daniel Perrett, Julie Phipps, Daniela T. Pilz, Martin Pollard, Caroline Pottinger, Joanna Poulton, Norman Pratt, Katrina Prescott, Sue Price, Abigail Pridham, Annie Procter, Hellen Purnell, Oliver Quarrell, Nicola Ragge, Raheleh Rahbari, Josh Randall, Julia Rankin, Lucy Raymond, Debbie Rice, Leema Robert, Eileen Roberts, Jonathan Roberts, Paul Roberts, Gillian Roberts, Alison Ross, Elisabeth Rosser, Anand Saggar, Shalaka Samant, Julian Sampson, Richard Sandford, Ajoy Sarkar, Susann Schweiger, Richard Scott, Ingrid Scurr, Ann Selby, Anneke Seller, Cheryl Sequeira, Nora Shannon, Saba Sharif, Charles Shaw-Smith, Emma Shearing, Debbie Shears, Eamonn Sheridan, Ingrid Simonic, Roldan Singzon, Zara Skitt, Audrey Smith, Kath Smith, Sarah Smithson, Linda Sneddon, Miranda Splitt, Miranda Squires, Fiona Stewart, Helen Stewart, Volker Straub, Mohnish Suri, Vivienne Sutton, Ganesh Jawahar Swaminathan, Elizabeth Sweeney, Kate Tatton-Brown, Cat Taylor, Rohan Taylor, Mark Tein, I. Karen Temple, Jenny Thomson, Marc Tischkowitz, Susan Tomkins, Audrey Torokwa, Becky Treacy, Claire Turner, Peter Turnpenny, Carolyn Tysoe, Anthony Vandersteen, Vinod Varghese, Pradeep Vasudevan, Parthiban Vijayarangakannan, Emma Wakeling, Sarah Wallwark, Jonathon Waters, Astrid Weber, Diana Wellesley, Margo Whiteford, Sara Widaa, Sarah Wilcox, Emily Wilkinson, Denise Williams, Nicola Williams, Louise Wilson, Geoff Woods, Christopher Wragg, Michael Wright, Laura Yates, Michael Yau, Chris Nellåker, Michael Parker, Helen V. Firth, Caroline F. Wright, David R. FitzPatrick, Jeffrey C. Barrett, Matthew E. Hurles, Department of Medicine 1, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Center for Medical Genetics, Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC, CNR), Istituto di Scienze e Tecnologie della Cognizione, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Department of Pediatrics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Centre de Génétique Chromosomique [Hôpital Saint Vincent de Paul], Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), Children’s Hospital of Philadelphia (CHOP ), Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Public Health Sciences, Karolinska Institutet [Stockholm], Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Università degli Studi di Camerino = University of Camerino (UNICAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Oxford, GeneDx [Gaithersburg, MD, USA], Department of Clinical Genetics (Academic Medical Center, University of Amsterdam), VU University Medical Center [Amsterdam], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Genetics, Aarhus University Hospital, Boston Children's Hospital, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Institute of Biomedical Engineering [Oxford] (IBME), Climatic Research Unit, University of East Anglia [Norwich] (UEA), Imperial College London, St Mary's Hospital, East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital, Sheffield Children's NHS Foundation Trust, Regional Genetic Service, St Mary's Hospital, Manchester, Genetics, University of Southampton, Great Ormond Street Hospital for Children [London] (GOSH), Yorkshire Regional Clinical Genetics Service, Chapel Allerton Hospital, Molecular and Clinical Medicine [Dundee, UK] (School of Medicine), University of Dundee [UK]-Ninewells Hospital & Medical School [Dundee, UK], Department of Clinical Genetics, Oxford Regional Genetics Service, The Churchill hospital, North West Thames Regional Genetics, Northwick Park Hospital, Royal Devon & Exeter Hospital, Wessex Clinical Genetics Service, Wessex clinical genetics service, Manchester University NHS Foundation Trust (MFT), West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Our Lady's hospital for Sick Children, Our Lady's Hospital for Sick Children, Guy's Hospital [London], University Hospitals Leicester, University of Edinburgh, Belfast City Hospital, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Institute of Medical Genetics, Heath Park, Cardiff, The London Clinic, Nottingham City Hospital, Clinical Genetics Department, St Michael's Hospital, Department of Genetic Medicine, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust (NUH), Royal Devon and Exeter Foundation Trust, Histopathology, St. George's Hospital, Teesside Genetics Unit, James Cook University (JCU), Kansas State University, Liverpool Women's NHS Foundation Trust, Department of Medical Genetics, HMNC Brain Health, North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow, Leicester Royal Infirmary, University Hospitals Leicester-University Hospitals Leicester, Ninewells Hospital and Medical School [Dundee], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Oxford Brookes University, Institute of medicinal plant development, Chinese Academy of Medical Sciences, Newcastle Upon Tyne Hospitals NHS Trust, Service d'explorations fonctionnelles respiratoires [Lille], Department of Computer Science - Trinity College Dublin, University of Dublin, Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust), Division of Medical & Molecular Genetics, NHS Greater Glasgow & Clyde [Glasgow] (NHSGGC), Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Weizmann Institute of Science [Rehovot, Israël], Southampton General Hospital, Western General Hospital, Head of the Department of Medical Genetics, University of Birmingham [Birmingham], SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, 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), All Wales Medical Genetics Services, Singleton Hospital, Central Manchester University Hospitals NHS Foundation Trust, University of North Texas (UNT), Clinical Genetics, Northern Genetics Service, Newcastle University [Newcastle], United Kingdom Met Office [Exeter], Institute of Medical Genetics (University Hospital of Wales), University Hospital of Wales (UHW), West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Department of Genetics, Cell- and Immunobiology, Semmelweis University, University Hospitals Bristol, Marketing (MKT), EESC-GEM Grenoble Ecole de Management, Addenbrookes Hospital, West of Scotland Genetics Service (Queen Elizabeth University Hospital), University Hospital Birmingham Queen Elizabeth, Department of Clnical Genetics, Chapel Allerton Hospital, Department of Clinical Genetics, Northampton General Hospital, Northampton, Royal Devon and Exeter Hospital [Exeter, UK] (RDEH), Guy's and St Thomas' Hospital [London], School of Computer Science, Bangor University, University Hospital Southampton, Clinical Genetics Unit, St Georges, University of London, Medical Genetics, Cardiff University, Research and Development, Futurelab, Nottingham Regional Genetics Service [Nottingham, UK], Nottingham University Hospitals NHS Trust (NUH)-City Hospital Campus [Nottingham, UK], University of St Andrews [Scotland], Clinical Genetics Service, Nottingham University Hospitals NHS Trust - City Hospital Campus, West Midlands Regional Genetics Unit, Department of Neurology, Johns Hopkins University (JHU), Oxford University Hospitals NHS Trust, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge University NHS Trust, Institute of Human Genetics, Newcastle, Division of Biological Stress Response [Amsterdam, The Netherlands], The Netherlands Cancer Institute [Amsterdam, The Netherlands], Johns Hopkins Bloomberg School of Public Health [Baltimore], Birmingham Women’s Hospital, Department of Genetics, Portuguese Oncology Institute, Molecular Genetics, IWK Health Centre, IWK health centre, North West london hospitals NHS Trust, Department of Clinical Genetics (Queen Elizabeth University Hospital, Glasgow), Queen Elizabeth University Hospital (Glasgow), Birmingham women's hospital, Birmingham, Ethox Centre, Department of Public Health and Primary Health Care, University of Oxford, Badenoch Building, Old Road Campus, Headington, R01 HD091846, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute, National Institutes of Health’s National Institute of Child Health and Human Development, Boston Children’s Hospital Faculty Development Fellowship, UM1HG008900, Broad Center for Mendelian Genomics, Chile’s National Commission for Scientific and Technological Research, DFG WE4896/3-1, German Research Society, WT 100127, Health Innovation Challenge Fund, Comprehensive Clinical Research Network, Skaggs-Oxford Scholarship, 10/H0305/83, Cambridge South REC, REC GEN/284/12, Republic of Ireland, WT098051, Wellcome Sanger Institute, 72160007, Comisión Nacional de Investigación Científica y Tecnológica, Children's Hospital of Philadelphia, Technische Universität Kaiserslautern, 1DH1813319, Dietmar Hopp Stiftung, National Institute for Health Research, Department of Health & Social Care, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Saint Vincent de Paul-GHICL, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Camerino (UNICAM), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Nottingham University Hospitals NHS Trust, Nottingham University Hospitals, SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, University Hospital of Wales, Grenoble Ecole de Management, Royal Devon and Exeter Hospital, City Hospital Campus [Nottingham, UK]-Nottingham University Hospitals NHS Trust [UK], ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, ACS - Pulmonary hypertension & thrombosis, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], GHICL-Hôpital Saint Vincent de Paul, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Friedrich-Alexander d'Erlangen-Nuremberg, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Bretagne Atlantique [Vannes], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], University of Zürich [Zürich] (UZH), Università di Camerino (UNICAM), Birmingham Women's Hospital Healthcare NHS Trust, University Hospitals of Leicester, Sheffield Children’s Hospital, Weizmann Institute of Science, and Grenoble Ecole de Management (GEM)
Subjects: 0301 basic medicine, Male, Microcephaly, [SDV]Life Sciences [q-bio], Haploinsufficiency, autism, epilepsy, epileptic encephalopathy, global developmental delay, H3K4 methylation, intellectual disability, KMT2E, neurodevelopmental disorder, Adolescent, Adult, Child, Child, Preschool, DNA-Binding Proteins, Epilepsy, Female, Humans, Infant, Neurodevelopmental Disorders, Pedigree, Phenotype, Young Adult, Genetic Variation, Heterozygote, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, Global developmental delay, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Hypotonia, 030220 oncology & carcinogenesis, medicine.symptom, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], 03 medical and health sciences, Report, medicine, Journal Article, Expressivity (genetics), Preschool, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Macrocephaly, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism, business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 206572.pdf (Publisher’s version ) (Open Access) We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
Published: 2019

9. Marine DNA Viral Macro- and Microdiversity from Pole to Pole

Author: Ann C. Gregory, Ahmed A. Zayed, Nádia Conceição-Neto, Ben Temperton, Ben Bolduc, Adriana Alberti, Mathieu Ardyna, Ksenia Arkhipova, Margaux Carmichael, Corinne Cruaud, Céline Dimier, Guillermo Domínguez-Huerta, Joannie Ferland, Stefanie Kandels, Yunxiao Liu, Claudie Marec, Stéphane Pesant, Marc Picheral, Sergey Pisarev, Julie Poulain, Jean-Éric Tremblay, Dean Vik, Marcel Babin, Chris Bowler, Alexander I. Culley, Colomban de Vargas, Bas E. Dutilh, Daniele Iudicone, Lee Karp-Boss, Simon Roux, Shinichi Sunagawa, Patrick Wincker, Matthew B. Sullivan, Silvia G. Acinas, Peer Bork, Emmanuel Boss, Guy Cochrane, Michael Follows, Gabriel Gorsky, Nigel Grimsley, Lionel Guidi, Pascal Hingamp, Olivier Jaillon, Stefanie Kandels-Lewis, Eric Karsenti, Fabrice Not, Hiroyuki Ogata, Nicole Poulton, Jeroen Raes, Christian Sardet, Sabrina Speich, Lars Stemmann, University of Exeter, Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Utrecht University [Utrecht], Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Takuvik Joint International Laboratory ULAVAL-CNRS, Université Laval [Québec] (ULaval)-Centre National de la Recherche Scientifique (CNRS), Université Laval [Québec] (ULaval), Observatoire océanologique de Villefranche-sur-mer (OOVM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Grenoble] (EMBL), Ohio State University [Columbus] (OSU), Institute of Marine Sciences / Institut de Ciències del Mar [Barcelona] (ICM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Maine, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wellcome Trust Genome Campus, Evolution des Protistes et Ecosystèmes Pélagiques (EPEP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Department of Earth, Atmospheric and Planetary Sciences [MIT, Cambridge] (EAPS), Massachusetts Institute of Technology (MIT), Biologie intégrative des organismes marins (BIOM), Observatoire océanologique de Banyuls (OOB), Stazione Zoologica Anton Dohrn (SZN), Génomique métabolique (UMR 8030), 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)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), European Molecular Biology Laboratory [Heidelberg] (EMBL), Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Pangea, Bigelow Laboratory for Ocean Sciences, Rega Institute - VIB Center for the Biology of Disease, Department of Microbiology and Immunology, Bioinformatics and (eco-)systems Biology Laboratory, Louvain, Belgique, Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Laboratoire de physique des océans (LPO), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), University of Arizona, Région Bretagne, Veolia Foundation, Fondation Prince Albert II de Monaco, Centre National de la Recherche Scientifique (France), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Laval [Québec] (ULaval)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Adaptation et diversité en milieu marin (ADMM), and Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR)
Subjects: Aquatic Organisms, [SDV]Life Sciences [q-bio], Coronacrisis-Taverne, species, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, marine biology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, General Biochemistry, Genetics and Molecular Biology, diversity gradients, Article, 03 medical and health sciences, 0302 clinical medicine, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Humans, Human virome, Ecosystem, 14. Life underwater, ComputingMilieux_MISCELLANEOUS, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, 030304 developmental biology, Marine biology, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, 0303 health sciences, metagenomics, Drowning, Community, Ecology, Microbiota, DNA Viruses, Biodiversity, DNA, Population ecology, Biodiversity hotspot, Arctic, 13. Climate action, Metagenomics, [SDU]Sciences of the Universe [physics], population ecology, DNA, Viral, Viruses, Metagenome, Water Microbiology, 030217 neurology & neurosurgery, community ecology, geographic locations
Abstract: 15 pages, 15 figures, 1 tables, supporting information https://doi.org/10.1016/j.cell.2019.03.040, Microbes drive most ecosystems and are modulated by viruses that impact their lifespan, gene flow, and metabolic outputs. However, ecosystem-level impacts of viral community diversity remain difficult to assess due to classification issues and few reference genomes. Here, we establish an ∼12-fold expanded global ocean DNA virome dataset of 195,728 viral populations, now including the Arctic Ocean, and validate that these populations form discrete genotypic clusters. Meta-community analyses revealed five ecological zones throughout the global ocean, including two distinct Arctic regions. Across the zones, local and global patterns and drivers in viral community diversity were established for both macrodiversity (inter-population diversity) and microdiversity (intra-population genetic variation). These patterns sometimes, but not always, paralleled those from macro-organisms and revealed temperate and tropical surface waters and the Arctic as biodiversity hotspots and mechanistic hypotheses to explain them. Such further understanding of ocean viruses is critical for broader inclusion in ecosystem models, Tara Oceans (that includes both the Tara Oceans and Tara Oceans Polar Circle expeditions) would not exist without the leadership of the Tara Expeditions Foundation and the continuous support of 23 institutes (https://oceans.taraexpeditions.org). We further thank the commitment of the following sponsors: CNRS (in particular Groupement de Recherche GDR3280 and the Research Federation for the study of Global Ocean Systems Ecology and Evolution, FR2022/Tara Oceans-GOSEE), European Molecular Biology Laboratory (EMBL), Genoscope/CEA, The French Ministry of Research, and the French Government “Investissements d’Avenir” programmes OCEANOMICS (ANR-11-BTBR-0008), FRANCE GENOMIQUE (ANR-10-INBS-09-08), MEMO LIFE (ANR-10-LABX-54), and PSL∗ Research University (ANR-11-IDEX-0001-02). We also thank the support and commitment of Agnès b. and Etienne Bourgois, the Prince Albert II de Monaco Foundation, the Veolia Foundation, Region Bretagne, Lorient Agglomeration, Serge Ferrari, Worldcourier, and KAUST
Published: 2019

10. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author: Igor Rudan, Daniel I. Chasman, Helena Schmidt, Stefan Herms, Sharon L.R. Kardia, Oliver Stegle, Alison Pattie, Jenna Price, Gerardo Heiss, Karen A. Mather, L. J. Launer, Johan G. Eriksson, Christopher Oldmeadow, Ian Ford, Saira Saeed Mirza, Alan F. Wright, Ozren Polasek, Joshua M. Shulman, Maria K. Jonsdottir, André G. Uitterlinden, Rodney J. Scott, Kurt Lohman, Anita L. DeStefano, Peter W. Schofield, Perminder S. Sachdev, Stefania Bandinelli, Johan Wouter Jukema, John M. Starr, Rudolf S N Fehrmann, Y. C. Hsieh, William M. Meeks, Paul M. Ridker, R.G.J. Westendorp, Le Yu, J. C. van Swieten, Vilmundur Gudnason, Myriam Fornage, Melissa Garcia, Carla A. Ibrahim-Verbaas, James F. Wilson, Jean-Charles Lambert, Qiong Yang, Laura H. Coker, Stella Trompet, Lina Zgaga, Jennifer A. Smith, David J. Llewellyn, Nicole A. Kochan, Ben A. Oostra, Katja Petrovic, Peter Hoffmann, Qi Sun, James T. Becker, Najaf Amin, Vincent Chouraki, Brendan M. Buckley, D C Liewald, Jun Ding, Christiane Wolf, P. L. DeJager, Reinhold Schmidt, Chloe Fawns-Ritchie, Stéphanie Debette, Jing Wang, J. C. Bis, Nicola J. Armstrong, David J. Stott, Albert Hofman, Nazanin Karbalai, G. Eiriksdottir, Luke C. Pilling, D. S. Knopman, Maaike Schuur, Alexa S. Beiser, Annette L. Fitzpatrick, David A. Bennett, Aarno Palotie, Lude Franke, Sven Cichon, Mirna Kirin, Markus M. Nöthen, Thomas H. Mosley, Lynda M. Rose, Alan J. Gow, Caroline Hayward, Lori B. Chibnik, Ian J. Deary, Albert V. Smith, Jan Bressler, T.B. Harris, Stephen T. Turner, David J. Porteous, C M van Duijn, M. A. Ikram, Elizabeth G. Holliday, Mike A. Nalls, Luigi Ferrucci, Sudha Seshadri, Francine Grodstein, Marlene C. W. Stewart, Philip A. Wolf, Alexander Teumer, P.E. Slagboom, Jerome I. Rotter, Blair H. Smith, Juha Karjalainen, Susan M. Resnick, A.J.M. de Craen, Toshiko Tanaka, Alan D. Penman, Hans-Jörgen Grabe, Gary Davies, Oscar L. Lopez, Yongmei Liu, Kristine Yaffe, Veronique Vitart, Stela McLachlan, Katri Räikkönen, Rebecca F. Gottesman, Rhoda Au, Lynne J. Hocking, Carsten Oliver Schmidt, John Attia, Bruce M. Psaty, Wei Zhao, Jari Lahti, Epidemiology, Neurology, Clinical Genetics, Internal Medicine, [ 1 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands [ 2 ] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands [ 3 ] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA [ 4 ] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA [ 5 ] Univ Bordeaux, Epidemiol & Biostat, U897, INSERM, Bordeaux, France [ 6 ] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France [ 7 ] Iceland Heart Assoc, Kopavogur, Iceland [ 8 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 9 ] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA [ 10 ] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland [ 11 ] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands [ 12 ] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands [ 13 ] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA [ 14 ] Max Planck Inst Psychiat, RG Stat Genet, Munich, Germany [ 15 ] Brigham & Womens Hosp, Div Neurol, Program Translat Neuropsychiat Gen, Boston, MA 02115 USA [ 16 ] Wake Forest Sch Med, Dept Epidemiol, Winston Salem, NC USA [ 17 ] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland [ 18 ] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland [ 19 ] Med Univ & Gen Hosp Graz, Dept Neurol, Graz, Austria [ 20 ] Univ Split, Dept Publ Hlth, Split, Croatia [ 21 ] Trintiy Coll Dublin, Dept Publ Hlth & Primary Care, Dublin, Ireland [ 22 ] Res Ctr Juelich, Inst Neurosci & Med INM1, Julich, Germany [ 23 ] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland [ 24 ] Univ Bonn, Inst Human Genet, Life & Brain Res Ctr, Dept Genom, Bonn, Germany [ 25 ] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands [ 26 ] Univ Helsinki, Inst Behav Sci, Helsinki, Finland [ 27 ] Folkhalsan Res Ctr, Helsinki, Finland [ 28 ] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England [ 29 ] Univ Med Greifswald, Inst Community Med, Greifswald, Germany [ 30 ] Univ New S Wales, UNSW Med, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia [ 31 ] Univ Lille Nord France, Inst Pasteur Lille, U1167, INSERM, Lille, France [ 32 ] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 33 ] Harvard Univ, Sch Med, Boston, MA USA [ 34 ] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA [ 35 ] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA [ 36 ] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia [ 37 ] Univ Newcastle, Fac Hlth, Newcastle, NSW 2300, Australia [ 38 ] Univ Dundee, Med Res Inst, Dundee, Scotland [ 39 ] NHLBI, Framingham Heart Study, Framingham, MA USA [ 40 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA [ 41 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands [ 42 ] Netherlands Consortium Hlth Ageing, Leiden, Netherlands [ 43 ] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA [ 44 ] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland [ 45 ] Wake Forest Sch Med, Div Publ Hlth Sci & Neurol, Winston Salem, NC USA [ 46 ] Max Planck Inst Intelligent Syst, Max Planck Inst Dev Biol, Tubingen, Germany [ 47 ] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA [ 48 ] Univ Med Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany [ 49 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland [ 50 ] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA [ 51 ] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA [ 52 ] Landspitali Hosp, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 53 ] NIA, Lab Neurogenet, Bethesda, MD 20892 USA [ 54 ] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA [ 55 ] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA [ 56 ] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA [ 57 ] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA [ 58 ] San Francisco VA Med Ctr, San Francisco, CA USA [ 59 ] Mayo Clin, Dept Neurol, Rochester, MN USA [ 60 ] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA [ 61 ] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA [ 62 ] Univ Newcastle, Fac Hlth, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia [ 63 ] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA [ 64 ] Univ Glasgow, Dept Cardiovasc & Med Sci, Glasgow, Lanark, Scotland [ 65 ] Alzheimer Scotland Res Ctr, Edinburgh, Midlothian, Scotland [ 66 ] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland [ 67 ] Garvan Inst Med Res, Canc Res Program, Sydney, NSW, Australia [ 68 ] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia [ 69 ] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia [ 70 ] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA [ 71 ] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Dept Mol & Human Genet, Houston, TX 77030 USA [ 72 ] Univ Exeter, Sch Med, Epidemiol & Publ Hlth Grp, Exeter, Devon, England [ 73 ] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia [ 74 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England [ 75 ] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland [ 76 ] Univ Helsinki, Dept Med Genet, Helsinki, Finland [ 77 ] Univ Cent Hosp, Helsinki, Finland [ 78 ] Taipei Med Univ, Sch Publ Hlth, Taipei, Taiwan [ 79 ] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland [ 80 ] Natl Inst Hlth & Welf, Helsinki, Finland [ 81 ] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland [ 82 ] Vasa Cent Hosp, Vaasa, Finland [ 83 ] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA [ 84 ] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA [ 85 ] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA [ 86 ] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA [ 87 ] Harbor UCLA Med Ctr, Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA [ 88 ] Harbor UCLA Med Ctr, Dept Pediat, Div Genet Outcomes, Torrance, CA 90509 USA [ 89 ] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany [ 90 ] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands [ 91 ] Leiden Acad Vital & Ageing, Leiden, Netherlands [ 92 ] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland [ 93 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 94 ] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA [ 95 ] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA [ 96 ] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA [ 97 ] HELIOS Hosp Stralsund, Univ Med Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany [ 98 ] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy [ 99 ] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland [ 100 ] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA [ 101 ] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA [ 102 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 103 ] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands [ 104 ] Univ Mississippi, Med Ctr, Dept Med & Neurol, Jackson, MS 39216 USA, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Stem Cell Aging Leukemia and Lymphoma (SALL)
Subjects: 0301 basic medicine, Male, DISORDER, Trail Making Test, LOCI, Genome-wide association study, INTELLIGENCE, Neuropsychological Tests, Cohort Studies, Exon, Executive Function, 0302 clinical medicine, Cognition, SCHIZOPHRENIA, ONSET ALZHEIMERS-DISEASE, CADM2 protein, human, genetics [Cell Adhesion Molecules], gamma-Aminobutyric Acid, Genetics, Aged, 80 and over, PSC12, physiology [Cognition], COMMON VARIANTS, Genomics, Middle Aged, genetics [Genetic Variation], 3. Good health, physiology [Executive Function], Psychiatry and Mental health, genetics [European Continental Ancestry Group], Schizophrenia, Female, Psychology, EXPRESSION, genetics [White People], physiology [Cell Adhesion Molecules], Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genetic variation, medicine, SNP, Humans, ddc:610, GENOME-WIDE ASSOCIATION, Molecular Biology, Gene, Genetic Association Studies, Aged, LINKAGE ANALYSIS, 9. Industry and infrastructure, Genetic Variation, medicine.disease, COGNITIVE FUNCTION, Introns, 030104 developmental biology, Cell Adhesion Molecules, 030217 neurology & neurosurgery, Stroop effect, Genome-Wide Association Study
Abstract: To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed. National Foundation for Alzheimer's disease and related disorders Institut Pasteur de Lille Centre National de Genotypage Inserm FRC (fondation pour la recherche sur le cerveau) Rotary LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease) MEDIALZ Project - ERDF (European Regional Development Fund) 11001003 Conseil Regional Nord Pas de Calais Fondation pour la Recherche Medicale Caisse Nationale Maladie des Travailleurs Salaries Direction Generale de la Sante MGEN Institut de la Longevite Agence Francaise de Securite Sanitaire des Produits de Sante Aquitaine and Bourgogne Regional Councils Fondation de France joint French Ministry of Research/INSERM 'Cohortes et collections de donnees biologiques' program Eisai Wellcome Trust British Heart Foundation Chief Scientist Office of the Scottish Executive NIA N01-AG-12100 National Heart, Lung and Blood Institute Contracts HHSN268201100005C HHSN268201100006C HHSN268201100007C HHSN268201100008C HHSN268201100009C HHSN268201100010C HHSN268201100011C HHSN268201100012C R01HL70825 R01HL087641 R01HL59367 R01HL086694 National Human Genome Research Institute U01HG004402 NIH Roadmap for Medical Research Austrian Science Fond (FWF) P20545-P05 P13180 Intramural Research Program of the NIH, National Institute on Aging NHLBI HHSN268201200036C HHSN268200800007C N01HC55222 N01HC85079 N01HC85080 N01HC85081 N01HC85082 N01HC85083 N01HC850863 U01HL080295 R01HL087652 R01HL105756 R01HL103612 R01HL120393 National Institute of Neurological Disorders and Stroke (NINDS) National Institute on Aging (NIA) R01AG023629 R01AG15928 R01AG20098 R01AG027058 National Center for Advancing Translational Sciences CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) DK063491 Medical Research Council (UK) European Commission Framework 6 project EUROSPAN LSHG-CT-2006-018947 Republic of Croatia Ministry of Science, Education and Sports 108-1080315-0302 Netherlands Organization for Scientific Research (NWO) Internationale Stichting Alzheimer Onderzoek (ISAO) Hersenstichting Nederland (HSN) Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI) Russian Foundation for Basic Research (RFBR) National Heart, Lung and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc N02-HL-6-4278 U01 HL096917 R01 HL093029 Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine Boston Medical Center National Institute of Neurological Disorders and Stroke NS17950 National Institute of Aging U01 AG049505 AG033193 AG008122 AG16495 Agence National de la Recherche Leducq Foundation National Heart, Lung and Blood Institute HL054464 HL054457 HL054481 HL071917 HL87660 HL043851 HL080467 National Institute of Neurological Disorders and Stroke of the National Institutes of Health NS041558 Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 Scottish Funding Council HR03006 Academy of Finland Finnish Diabetes Research Society Folkhalsan Research Foundation Novo Nordisk Foundation Finska Lakaresallskapet Signe and Ane Gyllenberg Foundation University of Helsinki Ministry of Education Ahokas Foundation Emil Aaltonen Foundation Juho Vainio Foundation Wellcome Trust WT089062 University of Newcastle's Strategic Initiative Fund Vincent Fairfax Family Foundation Hunter Medical Research Institute Italian Ministry of Health ICS 110.1RS97.71 US National Institute on Aging N01[AG]916413 N01[AG]821336 263 MD 9164 13 263 MD 821336 Intramural Research Program, National Institute on Aging, National Institutes of Health BBSRC Royal Society Chief Scientist Office of the Scottish Government Research Into Ageing UK Biotechnology and Biological Sciences Research Council (BBSRC) Engineering and Physical Sciences Research Council (EPSRC) Economic and Social Research Council (ESRC) MRC NHMRC 401184 Australian National Health & Medical Research Council 350833 568969 Capacity Building Grant 568940 NHMRC Project 525453 National Institutes of Health CA87969 CA49449 HL34594 U01HG004399 DK058845 CA65725 CA67262 CA50385 5UO1CA098233 EY09611 EY015473 HG004728 HL35464 CA55075 CA134958 DK070756 MRC Human Genetics Unit Arthritis Research UK European Union LSHG-CT-2006-018947 Bristol-Myers Squibb Netherlands Heart Foundation 2001 D 032 European commission 223004 Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) 050-060-810 Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project 050-060-810 Erasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission 49 (DG XII) Municipality of Rotterdam ZonMW Veni Grant 916.13.054 NIA Grants P30AG10161 R01AG15819 R01AG17917 R01AG30146 K08AG34290 K25AG41906 Federal Ministry of Education and Research 01ZZ9603 01ZZ0103 01ZZ0403 Ministry of Cultural Affairs Social Ministry of the Federal State of Mecklenburg-West Pomerania National Cancer Institute CA047988 Donald W Reynolds Foundation Fondation Leducq Amgen info:eu-repo/grantAgreement/EC/FP7/223004
Published: 2016

11. Easy and accurate reconstruction of whole HIV genomes from short-read sequence data with shiver

Author: BEEHIVE Collaboration, Wymant, Chris, Blanquart, Francois, Golubchik, Tanya, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela, Croucher, Nicholas J., Hall, Matthew, Hillebregt, Mariska, Ong, Swee Hoe, Ratmann, Oliver, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Fransen, Katrien, Gourlay, Annabelle, Grabowski, M. Kate, Gunsenheimer-Bartmeyer, Barbara, Gunthard, Huldrych F., Kivelä, Pia, Kouyos, Roger, Laeyendecker, Oliver, Liitsola, Kirsi, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Cornelissen, Marion, Kellam, Paul, Reiss, Peter, Fraser, Christophe, Institute for Particle Physics Phenomenology (IPPP), Durham University, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Evolution and Ecology Research Center, University of New South Wales [Sydney] (UNSW), Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Ecole Polytechnique Fédérale de Lausanne (EPFL), University College of London [London] (UCL), Universität Zürich [Zürich] = University of Zurich (UZH), Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Department of Medicine, The Johns Hopkins University School of Medicine-Division of Infectious Diseases, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Center for Infection and Immunity Amsterdam (CINIMA), Wellcome Trust Genome Campus, Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Big Data Institute, University of Oxford, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), University of Cambridge [UK] (CAM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Johns Hopkins University (JHU), Helsinki University Hospital [Finland] (HUS), Division of Intramural Research [Bethesda, MD, USA] (Cardiovascular Branch), National Institutes of Health [Bethesda] (NIH)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, THe BEEHIVE Collaboration, European Project: 339251,EC:FP7:ERC,ERC-2013-ADG,BEEHIVE(2014), AII - Infectious diseases, Medical Microbiology, APH - Aging & Later Life, Infectious diseases, Global Health, Clinicum, Infektiosairauksien yksikkö, HUS Inflammation Center, HUS Internal Medicine and Rehabilitation, and Bill & Melinda Gates Foundation
Subjects: 0301 basic medicine, PROTEASE, Computer science, Sequence assembly, RECOMBINATION, Computational biology, Microbiology, Genome, DNA sequencing, diversity, Set (abstract data type), 03 medical and health sciences, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:610, mapping, TYPE-1, ComputingMilieux_MISCELLANEOUS, Sequence (medicine), Contig, IDENTIFICATION, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], BEEHIVE Collaboration, HIV, INSERTIONS, food and beverages, bioinformatics, TRANSFORM, GENE, Resources, 3. Good health, Identification (information), ALIGNMENT, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, HUMAN-IMMUNODEFICIENCY-VIRUS, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, genome assembly, next-generation sequencing, 3111 Biomedicine, 610 Medizin und Gesundheit, INHIBITORS, Reference genome
Abstract: International audience; Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large betweenand within-host diversity, including frequent indels, may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to pre-process reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with the user’s choice of existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We used shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read whole-genome data produced with the Illumina platform, for sixty-five existing publicly available samples and fifty new samples. We show the systematic superiority of mapping to shiver’s constructed reference compared with mapping the same reads to the closest of 3,249 real references: median values of 13 bases called differently and more accurately, 0 bases called differently and less accurately, and 205 bases of missing sequence recovered. We also successfully applied shiver to whole-genome samples of Hepatitis C Virus and Respiratory Syncytial Virus. shiver is publicly available from https://github.com/ChrisHIV/shiver.
Published: 2018

12. Sixteen diverse laboratory mouse reference genomes define strain specific haplotypes and novel functional loci

Author: Leo Goodstadt, Mark Gerstein, Mark G. Thomas, Jingtao Lilue, Glen Threadgold, Fengtang Yang, Sarah Pelan, Jane E. Loveland, Kim Wong, Fabio C. P. Navarro, Jennifer Harrow, Ruth Bennett, Richard Durbin, Dent Earl, Monica Abrudan, Mario Stanke, David J. Adams, Adam Frankish, Son Pham, Anne Czechanski, Charles A. Steward, Jonathan Flint, Beiyuan Fu, Ian T. Fiddes, William Chow, Duncan T. Odom, Marcela K. Sjoberg-Herrera, Naomi Park, Paul Flicek, Anne C. Ferguson-Smith, James G. R. Gilbert, Lelliott C, Mikhail Kolmogorov, Mark Diekhans, Laura G. Reinholdt, Stefanie Nachtweide, Cristina Sisu, Thomas M. Keane, James Torrance, Richard Mott, Benedict Paten, Petr Danecek, Dirk-Dominik Dolle, Paul R. Muir, Ximena Ibarra-Soria, Stephan C. Collins, Binnaz Yalcin, Darren W. Logan, Lars Romoth, Matthew Dunn, Lesley Shirley, Kerstin Howe, David Thybert, Michael A. Quail, Clayton E. Mathews, Jonathan Wood, Anthony G. Doran, Joanna Collins, Joel Armstrong, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of California [Santa Cruz] (UCSC), University of California, The Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], 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), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), The Jackson Laboratory [Bar Harbor] (JAX), University of Cambridge [UK] (CAM), University of California [Los Angeles] (UCLA), Yale University [New Haven], OxAM House, University of California [San Diego] (UC San Diego), University of Florida [Gainesville] (UF), University College of London [London] (UCL), University of Greifswald, BioTuring Inc., Brunel University London [Uxbridge], Pontificia Universidad Católica de Chile (UC), University of Nottingham, UK (UON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Lilue, Jingtao [0000-0002-1958-0231], Diekhans, Mark [0000-0002-0430-0989], Flicek, Paul [0000-0002-3897-7955], Gerstein, Mark [0000-0002-9746-3719], Kolmogorov, Mikhail [0000-0002-5489-9045], Lelliott, Chris J [0000-0001-8087-4530], Logan, Darren W [0000-0003-1545-5510], Mott, Richard [0000-0002-1022-9330], Navarro, Fabio CP [0000-0002-5640-9070], Odom, Duncan T [0000-0001-6201-5599], Sjoberg-Herrera, Marcela [0000-0001-7173-048X], Thybert, David [0000-0001-7806-7318], Wong, Kim [0000-0002-0984-1477], Yalcin, Binnaz [0000-0002-1924-6807], Yang, Fengtang [0000-0002-3573-2354], Keane, Thomas M [0000-0001-7532-6898], Apollo - University of Cambridge Repository, University of California [Santa Cruz] (UC Santa Cruz), University of California (UC), and Julien, Sabine
Subjects: 0301 basic medicine, Transposable element, [SDV.IMM] Life Sciences [q-bio]/Immunology, Retrotransposon, Mice, Inbred Strains, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, Biology, de novo assembly, Genome, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Species Specificity, Mice, Inbred NOD, Animals, Laboratory, Genetics, Animals, Gene, mouse, Phylogeny, Mice, Inbred BALB C, Mice, Inbred C3H, Strain (biology), Haplotype, Laboratory mouse, allele, Chromosome Mapping, Molecular Sequence Annotation, Mice, Inbred C57BL, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Haplotypes, Genetic Loci, Mice, Inbred DBA, Mice, Inbred CBA, [SDV.IMM]Life Sciences [q-bio]/Immunology, subspecies, 030217 neurology & neurosurgery, Reference genome
Abstract: We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development. Medical Research Council and the Wellcome Trust
Published: 2018

13. Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

Author: Alberti, Adriana, Poulain, Julie, Engelen, Stefan, Labadie, Karine, Romac, Sarah, Ferrera, Isabel, Albini, Guillaume, Aury, Jean-Marc, Belser, Caroline, Bertrand, Alexis, Cruaud, Corinne, Da Silva, Corinne, Dossat, Carole, Gavory, Frédérick, Gas, Shahinaz, Guy, Guy, Haquelle, Maud, Jacoby, E'krame, Jaillon, Olivier, Lemainque, Arnaud, Pelletier, Eric, Samson, Gaëlle, Wessner, Mark, Bazire, Pascal, Beluche, Odette, Bertrand, Laurie, Besnard-Gonnet, Marielle, Bordelais, Isabelle, Boutard, Magali, Dubois, Maria, Dumont, Corinne, Ettedgui, Evelyne, Fernandez, Patricia, Garcia, Espérance, Aiach, Nathalie, Guerin, Thomas, Hamon, Chadia, Brun, Élodie, Lebled, Sandrine, Lenoble, Patricia, Louesse, Claudine, Mahieu, Eric, Mairey, Barbara, Martins, Nathalie, Megret, Catherine, Milani, Claire, Muanga, Jacqueline, Orvain, Céline, Payen, Emilie, Perroud, Peggy, Petit, Emmanuel, Robert, Dominique, Ronsin, Murielle, Vacherie, Benoit, Acinas, Silvia, Royo-Llonch, Marta, Cornejo-Castillo, Francisco, Logares, Ramiro, Fernández-Gómez, Beatriz, Bowler, Chris, Cochrane, Guy, Amid, Clara, Hoopen, Petra Ten, de Vargas, Colomban, Grimsley, Nigel, Desgranges, Elodie, Kandels-Lewis, Stefanie, Ogata, Hiroyuki, Poulton, Nicole, Sieracki, Michael, Stepanauskas, Ramunas, Sullivan, Matthew, Brum, Jennifer, Duhaime, Melissa, Poulos, Bonnie, Hurwitz, Bonnie, Bork, Peer, Boss, Emmanuel, Follows, Michael, Gorsky, Gabriel, Hingamp, Pascal, Iudicone, Daniele, Karp-Boss, Lee, Karsenti, Eric, Not, Fabrice, Pesant, Stéphane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Stemmann, Lars, Sunagawa, Shinichi, Wincker, Patrick, CNS, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Evolution des Protistes et Ecosystèmes Pélagiques (EPEP), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institute of Marine Sciences / Institut de Ciències del Mar [Barcelona] (ICM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unité Mathématique Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), Centre National de Génotypage (CNG), Universidad Politécnica de Madrid (UPM), Structure et évolution des génomes (SEG), CNS-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Université de Toulon - Faculté de Droit de Toulon (UTLN UFR Droit), Université de Toulon (UTLN), Actilia Multimedia, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV)-Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Université d'Artois (UA)-Université de Liège-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Grande Rue, Auteur indépendant, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Informatics Department, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Biologie intégrative des organismes marins (BIOM), Observatoire océanologique de Banyuls (OOB), European Molecular Biology Laboratory [Heidelberg] (EMBL), Bigelow Laboratory for Ocean Sciences, University of Arizona, Ecology and Evolutionary Biology [Tucson] (EEB), European Molecular Biology Laboratory, School of Marine Sciences, University of Maine, Department of Earth, Atmospheric and Planetary Sciences [MIT, Cambridge] (EAPS), Massachusetts Institute of Technology (MIT), Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Stazione Zoologica Anton Dohrn (SZN), Diversité et Interactions au sein du Plancton Océanique (DIPO), Center for Marine Environmental Sciences [Bremen] (MARUM), Universität Bremen, Department of Bioscience Engineering, Vrije Universiteit Brussel (VUB), Groupe de Biologie Marine du CEA, Laboratoire de physique des océans (LPO), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'Energie Atomique, Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Adaptation et diversité en milieu marin (ADMM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble, LIttoral ENvironnement et Sociétés - UMR 7266 (LIENSs), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), EA 3900 BIOPI Laboratoire de Phytotechnologie, Université de Picardie Jules Verne (UPJV), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Stazione Zoologica Anton Dohrn, Vrije Universiteit [Brussels] (VUB), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

14. Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe

Author: Annabelle Gourlay, Kirsi Liitsola, Huldrych F. Günthard, Swee Hoe Ong, Norbert Bannert, Mariska Hillebregt, Jan Albert, Katrien Fransen, Oliver Laeyendecker, Barbara Gunsenheimer-Bartmeyer, François Blanquart, Astrid Gall, Peter Reiss, Ben Berkhout, Marion Cornelissen, Guido Vanham, Pia Kivelä, Matti Ristola, Daniela Bezemer, Kholoud Porter, Roger D. Kouyos, Margreet Bakker, M. Kate Grabowski, Matthew Hall, Laurence Meyer, Ard van Sighem, Christophe Fraser, Chris Wymant, Jacques Fellay, Paul Kellam, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique d'Orsay [Orsay] (LPT), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Center for Infection and Immunity Amsterdam (CINIMA), University of Cambridge [UK] (CAM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Edinburgh, Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Tropical Medicine [Antwerp] (ITM), University College of London [London] (UCL), Department of Medicine, The Johns Hopkins University School of Medicine-Division of Infectious Diseases, Helsinki University Hospital [Finland] (HUS), Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Division of Intramural Research [Bethesda, MD, USA] (Cardiovascular Branch), National Institutes of Health [Bethesda] (NIH)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Wellcome Trust Genome Campus, Synthèse, Structure et Propriétés de Matériaux Fonctionnels (STEP), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford, AII - Infectious diseases, Medical Microbiology and Infection Prevention, AII - Amsterdam institute for Infection and Immunity, APH - Aging & Later Life, Global Health, University of Helsinki, Infektiosairauksien yksikkö, Clinicum, HUS Inflammation Center, HUS Internal Medicine and Rehabilitation, Medical Research Council (MRC), and Commission of the European Communities
Subjects: Male, Epidemiology, HIV Infections, Pathology and Laboratory Medicine, 0302 clinical medicine, Immunodeficiency Viruses, HIV Seropositivity, Biology (General), Phylogeny, education.field_of_study, HERITABILITY, BEEHIVE collaboration, Phylogenetic Analysis, 11 Medical And Health Sciences, Medical Microbiology, Viral Pathogens, General Agricultural and Biological Sciences, Viral load, AFRICA, Biochemistry & Molecular Biology, QH301-705.5, Microbiology, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, 03 medical and health sciences, Genetics, Humans, Evolutionary Systematics, education, Biology, Microbial Pathogens, Aged, Science & Technology, Organisms, Genetic Variation, Correction, 06 Biological Sciences, 030104 developmental biology, Genetic epidemiology, HIV-1, 07 Agricultural And Veterinary Sciences, Developmental Biology, Life Sciences & Biomedicine - Other Topics, Evolutionary Genetics, RNA viruses, 0301 basic medicine, [SDV]Life Sciences [q-bio], Human Immunodeficiency Virus Proteins, RNA LEVELS, Cohort Studies, INFECTION, PROGNOSTIC MARKERS, Medicine and Health Sciences, Registries, 030212 general & internal medicine, Data Management, PLASMA, Virulence, Phylogenetic tree, General Neuroscience, Microbial Genetics, IMMUNODEFICIENCY-VIRUS TYPE-1, Middle Aged, Viral Load, Regression, Phylogenetics, Europe, Seroconversion, Genetic Epidemiology, Viral evolution, Viruses, Viral Genetics, Female, Pathogens, Life Sciences & Biomedicine, Research Article, Adult, Computer and Information Sciences, TRANSMISSION, Population, Genome, Viral, Viral Evolution, Virology, Retroviruses, Genetic variation, Taxonomy, Evolutionary Biology, Biology and life sciences, Models, Genetic, General Immunology and Microbiology, Lentivirus, HIV, Heritability, Organismal Evolution, 3121 General medicine, internal medicine and other clinical medicine, Microbial Evolution, 1182 Biochemistry, cell and molecular biology, Viral Transmission and Infection, Genome-Wide Association Study
Abstract: HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%–43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical “Brownian motion” model and another model (“Ornstein–Uhlenbeck”) that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%–43%) is consistent with other studies based on regression of viral load in donor–recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation., Author summary The severity of the outcome of infection by a pathogen depends on many distinct factors. These include the environment and the genetic sequences of both the host and the pathogen, among others. The fraction of variability in disease outcome explained by pathogen genetic factors is termed “heritability”, because these factors are “inherited” by the new host upon infection. Quantifying heritability is key to understanding the development of the disease and the evolution of the virus. Here, we determined heritability of set-point viral load (SPVL) in HIV-1. SPVL is the stable value of viraemia in asymptomatic infection and it is a strong predictor of disease severity. While heritability of SPVL has been estimated using comparisons of viral genome sequences, this has resulted in widely variable estimates of heritability. Using a large dataset of patients living in Europe, standardised viral loads measures, and new methods, we obtain a more definitive estimate of HIV-1 SPVL heritability in Europe at about 30%. Thus, a significant amount of the variation in disease outcome is explained by the genetics of the virus.
Published: 2017

15. SC83288 is a clinical development candidate for the treatment of severe malaria

Author: Vicky M. Avery, Cecilia P. Sanchez, Stefanie K. Fehler, Henri Vial, Roman Rösemann, Thomas D. Otto, Michael Lanzer, Maëlle Duffey, Yulin Wang, Roland Baumgartner, Leonardo Lucantoni, Stefan Strobl, Dominique Mazier, Stefano Pegoraro, Alicia Moreno-Sabater, 4SC AG, Heidelberg University Hospital [Heidelberg], German Centre for Infection Research (DZIF), Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], 4SC Discovery, Griffith University [Brisbane], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Parasitologie - Mycologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Science, 030106 microbiology, General Physics and Astronomy, Safety margin, Nod, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Amicarbalide, parasitic diseases, Medicine, Severe Malaria, Mode of action, Multidisciplinary, biology, business.industry, Plasmodium falciparum, General Chemistry, biology.organism_classification, 3. Good health, 030104 developmental biology, Falciparum infection, Immunology, business, Scid mouse model, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P. falciparum infection in a humanized NOD/SCID mouse model system. Detailed preclinical pharmacokinetic and toxicological studies reveal no observable drawbacks. Ultra-deep sequencing of resistant parasites identifies the sarco/endoplasmic reticulum Ca2+ transporting PfATP6 as a putative determinant of resistance to SC81458 and SC83288. Features, such as fast parasite killing, good safety margin, a potentially novel mode of action and a distinct chemotype support the clinical development of SC83288, as an intravenous application for the treatment of severe malaria.
Published: 2017

16. The metagenomic data life-cycle: standards and best practices

Author: Alex L. Mitchell, Graziano Pesole, Petra ten Hoopen, Robert D. Finn, Bruno Fosso, Lars Ailo Bongo, Eric Pelletier, Nils Peder Willassen, Guy Cochrane, Monica Santamaria, Folker Meyer, Erwan Corre, Wellcome Trust Genome Campus, The Arctic University of Norway [Tromsø, Norway] (UiT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CNR - Bari, Argonne National Lab., Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université d'Évry-Val-d'Essonne (UEVE), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), The Arctic University of Norway, University of Bari Aldo Moro (UNIBA), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: 0301 basic medicine, sampling, [SDV]Life Sciences [q-bio], Best practice, best practice, data analysis, Health Informatics, Review, Biology, VDP::Matematikk og Naturvitenskap: 400::Informasjons- og kommunikasjonsvitenskap: 420, Workflow, 03 medical and health sciences, Marine research, VDP::Mathematics and natural science: 400::Information and communication science: 420, 0302 clinical medicine, Databases, Genetic, Data Mining, Repurposing, metadata, Computational Biology, Sampling (statistics), standard, sequencing, Data life cycle, Data science, Computer Science Applications, Metadata, 030104 developmental biology, Metagenomics, Metagenome, Sequence Analysis, 030217 neurology & neurosurgery
Abstract: Source at https://doi.org/10.1093/gigascience/gix047. Accepted manuscript version, licensed CC BY-NC-ND 4.0. Metagenomics data analyses from independent studies can only be compared if the analysis workflows are described in a harmonized way. In this overview, we have mapped the landscape of data standards available for the description of essential steps in metagenomics: (i) material sampling, (ii) material sequencing, (iii) data analysis, and (iv) data archiving and publishing. Taking examples from marine research, we summarize essential variables used to describe material sampling processes and sequencing procedures in a metagenomics experiment. These aspects of metagenomics dataset generation have been to some extent addressed by the scientific community, but greater awareness and adoption is still needed. We emphasize the lack of standards relating to reporting how metagenomics datasets are analysed and how the metagenomics data analysis outputs should be archived and published. We propose best practice as a foundation for a community standard to enable reproducibility and better sharing of metagenomics datasets, leading ultimately to greater metagenomics data reuse and repurposing.
Published: 2017

17. Genomic analyses inform on migration events during the peopling of Eurasia

Author: N. V. Ekomasova, Elza Khusnutdinova, Andrea Bamberg Migliano, Vedrana Škaro, Georgi Hudjashov, L. A. Atramentova, Murray P. Cox, Evelin Mihailov, Marta Mirazón Lahr, Mait Metspalu, Herawati Sudoyo, Monika Karmin, Alexia Cardona, Florin Mircea Iliescu, Melissa A. Wilson Sayres, Bayazit Yunusbayev, Dilbar Dalimova, Boris Malyarchuk, Michael D. Petraglia, Rita Khusainova, Grigor Zoraqi, Mark G. Thomas, Gazi Nurun Nahar Sultana, Irina Evseeva, Kuvat T. Momynaliev, François-Xavier Ricaut, Jainagul Isakova, A. S. Karunas, Reedik Mägi, Joseph Lachance, Kristiina Tambets, Lejla Mulahasanovic, Elena Balanovska, S M Abdullah, Levon Yepiskoposyan, Oleg Balanovsky, Nicolas Brucato, Yali Xue, Lauri Saag, Andrea Manica, Christina A. Eichstaedt, Mario Mitt, Florian Clemente, Ene Metspalu, Sardana A. Fedorova, Chris Tyler-Smith, Andres Metspalu, Charlotte E. Inchley, Pagbajabyn Nymadawa, Matthew Leavesley, Marina Gubina, Guy S. Jacobs, David M. Lambert, Craig Muller, Thierry Letellier, Elvira Pocheshkhova, Qasim Ayub, Joseph Wee, Pascale Gerbault, Zhaxylyk Sabitov, Doron M. Behar, Nikolay A. Barashkov, Dragan Primorac, Christiana L. Scheib, Tiago Antao, Evelyn Jagoda, Olga Utevska, Jeffrey D. Wall, Sarah A. Tishkoff, Toomas Kivisild, Gyaneshwer Chaubey, Shahlo Turdikulova, Eske Willerslev, Alena Kushniarevich, Lehti Saag, Chandana Basu Mallick, I. M. Khidiyatova, Ludmila P. Osipova, Alexander Mörseburg, Hovhannes Sahakyan, Damir Marjanović, Larisa Damba, Richard Villems, Anders Eriksson, Miroslava Derenko, Sergei Litvinov, Daniel Lawson, Rasmus Nielsen, V. L. Akhmetova, Maru Mormina, Mari Järve, Luca Pagani, George Andriadze, Michael DeGiorgio, Mikhail Voevoda, Daria V. Lichman, Michael C. Westaway, Sarah Kaewert, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Human Evolution, University of Pennsylvania [Philadelphia], Institute of Molecular Biology and Medicine, International Network for the Sequencing of resPIRratory vIrusEs (INSPIRE), Department of Oncology, Human Genetics, Physiopathologie mitochondriale, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Leverhulme Centre for Human Evolutionary Studies University of Cambridge, University of Cambridge [UK] (CAM), The Estonian Genome Center, University of Tartu, Institute of Cytology and Genetics, Russian Academy of Sciences [Moscow] (RAS), School of Archaeology, University of Oxford [Oxford], Russian Academy of Medical Sciences, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], Dept Integrat Biol, UMR 6578 : Anthropologie Bio-Culturelle (UAABC), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Section for GeoGenetics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Swedish Institute of Space Physics [Uppsala] (IRF), University of Pennsylvania, University of Oxford, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Eriksson, Anders [0000-0003-3436-3726], Cardona, Alexia [0000-0002-7877-5565], Scheib, Christiana [0000-0003-4158-8296], Jacobs, Guy [0000-0002-4698-7758], Mirazon Lahr, Marta [0000-0001-5752-5770], Manica, Andrea [0000-0003-1895-450X], Willerslev, Eske [0000-0002-7081-6748], Kivisild, Toomas [0000-0002-6297-7808], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, History, Native Hawaiian or Other Pacific Islander, Biological anthropology, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Population Dynamics, Datasets as Topic, Evolutionary biology, Balancing selection, Genome, genome, peopling, Eurasia, 0302 clinical medicine, Effective population size, History, Ancient, Neanderthals, Genetics, education.field_of_study, Multidisciplinary, Continental Population Groups, Human migration, Fossils, Medicine (all), Genomics, 3. Good health, Europe, Oceanic Ancestry Group, Human, Biotechnology, Estonia, Gene Flow, Genome evolution, Heterozygote, Asia, General Science & Technology, 1.1 Normal biological development and functioning, Human Migration, Population, Biology, Evolutionary genetics, Article, Ancient, Africa, Animals, Genetics, Population, Genome, Human, Humans, New Guinea, 03 medical and health sciences, education, business.industry, Human evolutionary genetics, Racial Groups, Human Genome, 030104 developmental biology, Generic health relevance, business, 030217 neurology & neurosurgery
Abstract: High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2, 3, 4, 5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high- resolution genomic data has led to the development of new methodologies for inferring population history7, 8, 9 and refuelled the debate on the mutation rate in humans10. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75, 000 years ago.
Published: 2016

18. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

Author: Richard H. Duerr, Dalin Li, Ming-Hsi Wang, Tariq Ahmad, John D. Rioux, Patrick Sulem, Daniel B. Graham, Steven R. Brant, Severine Vermeire, Mark Tremelling, James Lee, Leena Halme, K. de Lane, Miguel Regueiro, M Parkes, David C. Wilson, Alain Bitton, R. Milgrom, Daniel G. MacArthur, Marijn C. Visschedijk, Sören Mucha, Kenneth Croitoru, Alison Simmons, Mark S. Silverberg, Rinse K. Weersma, Jonas Halfvarson, Daniel L. Rice, J. M. Stempak, Christopher J. Hawkey, Mauro D'Amato, Christopher G. Mathew, Philippe Goyette, Frauke Degenhardt, Daniel F. Gudbjartsson, Mark J. Daly, Kari Stefansson, Beryl B. Cummings, Maarit Lappalainen, Päivi Saavalainen, Paulina Paavola-Sakki, P. Fleshner, Talin Haritunians, Joshua C. Randall, Elaine R. Nimmo, Taru Tukiainen, Christine Stevens, Subra Kugathasan, Monkol Lek, Andre Franke, Kimmo Kontula, Unnur Thorsteinsdottir, Andrew Hart, Martin O. Pollard, Gabrielle Boucher, Natalie J. Prescott, Benjamin M. Neale, Holm H. Uhlig, Carl A. Anderson, Ashwin N. Ananthakrishnan, Luke Jostins, C. Mowatt, Judy H. Cho, B. Newman, A. Nicole Desch, Yang Luo, Dermot P.B. McGovern, Clara Abraham, Ingileif Jonsdottir, Jeffrey C. Barrett, John C. Mansfield, Jean-Paul Achkar, Charlie W. Lees, Martti Färkkilä, Ramnik J. Xavier, S. R. Targan, Manuel A. Rivas, Deborah D. Proctor, Johan Van Limbergen, Nicholas A. Kennedy, Christopher A. Lamb, Jürgen Glas, Vito Annese, Yashoda Sharma, Phil Schumm, Graham A. Heap, Cathryn Edwards, Lotta L. E. Koskinen, Jack Satsangi, Mitja I. Kurki, Aarno Palotie, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA deCODE Genetics, Amgen Inc., 101 Reykjavik, Iceland Research Center, Montreal Heart Institute, Montréal, Québec, Canada H1T1C8 School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland Department of Immunology, Landspitali, the National University Hospital of Iceland, 101 Reykjavik, Iceland Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048 USA Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Stockholm, Sweden BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, 48903 Bilbao, Spain Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, 71013 San Giovanni Rotondo, Italy Strutture Organizzative Dipartimentali (SOD) Gastroenterologia 2, Azienda Ospedaliero Universitaria (AOU) Careggi, 50134 Florence, Italy Department of Clinical and Experimental Medicine, Translational Research in GastroIntestinal Disorders (TARGID), Katholieke Universiteit (KU) Leuven, Leuven 3000, Belgium Division of Gastroenterology, University Hospital Gasthuisberg, BE-3000 Leuven, Belgium Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, The Netherlands Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, SE 701 82 Örebro, Sweden Department of Medicine, University of Helsinki, 00100 Helsinki, Finland Helsinki University Hospital, 00100 Helsinki, Finland Clinic of Gastroenterology, Helsinki University Hospital, 00100 Helsinki, Finland Research Programs Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland Department of Transplantation and Liver Surgery, University of Helsinki, 00100 Helsinki, Finland Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00100 Helsinki, Finland Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02114, USA Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK IBD Pharmacogenetics, Royal Devon and Exeter NHS Trust, Exeter EX2 5DW, UK Graham A. Heap Peninsula College of Medicine and Dentistry, Exeter PL6 8BU, UK Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205, USA Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, USA Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA Department of Medicine, Inflammatory Bowel Disease Centre, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06510, USA Institute for Molecular Medicine Finland, University of Helsinki, 00100 Helsinki, Finland Massachusetts General Hospital, Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Boston, Massachusetts 02114, USA Research Programs Unit, Immunobiology, University of Helsinki, 00100 Helsinki, Finland Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4 Department of Gastroenterology, Torbay Hospital, Devon, UK Department of Medicine, St. Mark’s Hospital, Middlesex, UK Nottingham Digestive Disease Centre, Queens Medical Centre, Nottingham, UK Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK Christ Church, University of Oxford, Oxford, UK Gastrointestinal Unit, Wester General Hospital, University of Edinburgh, Edinburgh, UK Newcastle University, Newcastle upon Tyne, UK Inflammatory Bowel Disease Research Group, Addenbrooke’s Hospital, Cambridge, UK Department of Medical and Molecular Genetics, Guy’s Hospital, London, UK Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, London, UK Department of Medicine, Ninewells Hospital and Medical School, Dundee, UK Genetic Medicine, Manchester Academic Health Science Centre, Manchester, UK The Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK Gastroenterology & General Medicine, Norfolk and Norwich University Hospital, Norwich, UK Translational Gastroenterology Unit and the Department of Pediatrics, University of Oxford, Oxford, UK Pediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK Child Life and Health, University of Edinburgh, Edinburgh, UK Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Division of Gastroenterology, Royal Victoria Hospital, Montréal, Québec, Canada Inflammatory Bowel Disease Group, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA, Department of Medicine, Clinicum, Gastroenterologian yksikkö, Immunobiology Research Program, Research Programs Unit, Department of Medical and Clinical Genetics, Medicum, II kirurgian klinikka, Department of Surgery, Institute for Molecular Medicine Finland, Aarno Palotie / Principal Investigator, Immunomics, Kimmo Kontula Research Group, and Genomics of Neurological and Neuropsychiatric Disorders
Subjects: 0301 basic medicine, AAI12, Chemistry(all), SUSCEPTIBILITY LOCI, Science, Population, General Physics and Astronomy, Physics and Astronomy(all), OF-FUNCTION VARIANTS, Inflammatory bowel disease, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, NUMBER, medicine, Ring finger, IMPUTATION, Allele, education, POPULATION, RISK, education.field_of_study, Multidisciplinary, biology, Biochemistry, Genetics and Molecular Biology(all), MUTATIONS, General Chemistry, ASSOCIATION, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Ubiquitin ligase, Transport protein, Transmembrane domain, 030104 developmental biology, medicine.anatomical_structure, RARE VARIANTS, Immunology, biology.protein, Cancer research, 3111 Biomedicine, INFLAMMATORY-BOWEL-DISEASE
Abstract: To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain. National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) DK064869 DK062432 National Human Genome Research Institute (NHGRI) DK064869 DK043351 HG005923 Crohns and Colitis Foundation 3765 Leona M. & Harry B. Helmsley Charitable Trust 2015PG-IBD001 Amgen 2013583217 CCFA 3765 Cedars-Sinai F. Widjaja Foundation, info:eu-repo/grantAgreement/EC/FP7/305479, European Union DK062413 AI067068 U54DE023789-01 Leona M. and Harry B. Helmsley Charitable Trust Crohn's and Colitis Foundation of America NIH DK062431 U01 DK062429 U01 DK062422 R01 DK092235 U01 DK062420 Medical Research Council, UK MR/J00314X/1 Wellcome Trust WT091310 098051 Inflammatory Bowel Disease Genetic Research Chair at the University of Pittsburgh PO1DK046763
Published: 2016

19. HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

Author: Ari Karason, Jeffrey C. Barrett, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Adalbjorg Jonasdottir, Kai Blöndal, Olafur Th Magnusson, Aslaug Jonasdottir, Hafdis T. Helgadottir, Larus J. Gudmundsson, Helgi Kristjansson, Yang Luo, Kari Stefansson, Gardar Sveinbjornsson, Gisli Masson, Mar Kristjansson, Arnaldur Gylfason, Augustine Kong, Ljiljana Bulat Kardum, Sigurjon A. Gudjonsson, Ingileif Jonsdottir, Arthur Löve, Jelena Knežević, Magnus Gottfredsson, Bjarni V. Halldorsson, Thorsteinn Blondal, Zlatko Dembic, Sergey Nejentsev, Karl G. Kristinsson, Patrick Sulem, and [ 1 ] Amgen Inc, deCODE Genet, Reykjavik, Iceland [ 2 ] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland [ 3 ] Reykjavik Univ, Sch Sci & Engn, Reykjavik, Iceland [ 4 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland [ 5 ] Natl Univ Hosp Iceland, Dept Clin Microbiol, Landspitali, Reykjavik, Iceland [ 6 ] Natl Univ Hosp Iceland, Dept Infect Dis, Landspitali, Reykjavik, Iceland [ 7 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England [ 8 ] Primary Hlth Care Capital Area, Div Communicable Dis Prevent & Control, Reykjavik, Iceland [ 9 ] Univ Rijeka, Dept Pulmonol, Clin Internal Med, Clin Hosp Ctr, Rijeka, Croatia [ 10 ] Univ Oslo, Fac Dent, Dept Oral Biol, Mol Genet Lab, Oslo, Norway [ 11 ] Rudjer Boskovic Inst, Div Mol Med, Zagreb, Croatia [ 12 ] Natl Univ Hosp Iceland, Landspitali, Dept Virol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 13 ] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England [ 14 ] Natl Univ Hosp Iceland, Landspitali, Dept Immunol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital
Subjects: 0301 basic medicine, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, T-Lymphocytes, Iceland, Genome-wide association study, TMD12, 0302 clinical medicine, Gene Frequency, Risk Factors, Genetics, variants, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Berklar, 3. Good health, Europe, BAC12, tuberculosis, 030220 oncology & carcinogenesis, NAF12, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, Tuberculosis, Human leukocyte antigen, Biology, Article, HLA-DQ alpha-Chains, White People, 03 medical and health sciences, Antigen, medicine, Humans, Genetic Predisposition to Disease, HLA class II, Allele, Tuberculosis, Pulmonary, Allele frequency, Alleles, PAD12, Genome, Human, HLA-DR Antigens/genetics, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Genetic Variation, Mycobacterium tuberculosis, Odds ratio, Arfgengi, medicine.disease, Virology, Tuberculosis, Pulmonary/genetics, Minor allele frequency, 030104 developmental biology, Genome-Wide Association Study, HLA-DRB1 Chains
Abstract: To access publisher's full text version of this article click on the hyperlink at the bottom of the page Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))-both located between HLA-DQA1 and HLA-DRB1-and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells. US National Institute of Allergy and Infectious Diseases HHSN266200400064C UK Wellcome Trust 088838/Z/09/Z 095198/Z/10/Z info:eu-repo/grantAgreement/EC/FP7/201483 European Research Council Starting 260477 Royal Society UF0763346 RG090638 Wellcome Trust Senior Research fellowship National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
Published: 2016

20. 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

21. Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes

Author: Ina Poser, Annelie Wünsche, Cihan Cetin, Jan Ellenberg, Daniel W. Gerlich, Frank Sieckmann, Venkata P. Satagopam, Holger Erfle, Anthony A. Hyman, Reinhard Schneider, Michael Held, Catherine Chapuis, Michael H.A. Schmitz, Jutta Bulkescher, Wolfgang Huber, Christian Conrad, Roland Eils, Jean-Karim Hériché, Richard Durbin, Rainer Pepperkok, Rolf Kabbe, Urban Liebel, Jan-Michael Peters, Thomas Walter, Gregoire Pau, Phill Rogers, Beate Neumann, University of Zurich, Ellenberg, J, European Molecular Biology Laboratory [Heidelberg] (EMBL), Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), BioQuant, Heidelberg University, Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Leica Microsystems CMS GmbH, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Division of Theoretical Bioinformatics [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Research institute for molecular pathology, Universität Wien, The Wellcome Trust Sanger Institute [Cambridge], Department of Informatics, university of Hamburg, MINES ParisTech - École nationale supérieure des mines de Paris - PSL Research University (PSL), Immunité et cancer, Université Paris Descartes - Paris 5 (UPD5) - Institut Curie - Institut National de la Santé et de la Recherche Médicale (INSERM), Max Planck Institute, Laboratoire Réactions et Génie des Procédés (LRGP), Université de Lorraine (UL) - Centre National de la Recherche Scientifique (CNRS), Wellcome Trust Genome Campus, Cell Biology and Cell Biophysics Unit, European Molecular Biology Laboratory, European Molecular Biology Laboratory [Grenoble] (EMBL), and Cell Biology and Biophysics Unit
Subjects: Genetics, 0303 health sciences, 1000 Multidisciplinary, Multidisciplinary, Cell division, Phenotypic screening, Genomics, 610 Medicine & health, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 11359 Institute for Regenerative Medicine (IREM), Biology, Biochemistry, biophysics & molecular biology [F05] [Life sciences], Proteomics, Genome, 03 medical and health sciences, 0302 clinical medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Human genome, Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], Gene, Functional genomics, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the approximately 21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.
Published: 2010
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22. Tibiofemoral contact forces during walking, running and sidestepping

Author: Tim V. Wrigley, David J. Saxby, Karine Fortin, Bryce A. Killen, Kim L Bennell, Luca Modenese, David Lloyd, Adam L. Bryant, Flavia M. Cicuttini, Pauline Gerus, INSIGNEO Institute for in Silico Medicine, University of Sheffield [Sheffield], Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), Informatics Department, Wellcome Trust Genome Campus, and The Wellcome Trust Sanger Institute [Cambridge]
Subjects: Male, 02 engineering and technology, Electromyography, Walking, EMG-driven model, Running, 0302 clinical medicine, Gait (human), Orthopedics and Sports Medicine, Muscle activity, Gait, ComputingMilieux_MISCELLANEOUS, IN-VIVO, Mathematics, 1106 Human Movement And Sports Science, medicine.diagnostic_test, Sidestepping, Rehabilitation, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Biomechanical Phenomena, Adduction moment, Musculoskeletal models, Female, Life Sciences & Biomedicine, 0913 Mechanical Engineering, Adult, medicine.medical_specialty, STRATEGIES, Joint contact forces, 0206 medical engineering, LOADS, Biophysics, Joint stability, Knee adduction moment, PREDICTIONS, Contact force, 03 medical and health sciences, Physical medicine and rehabilitation, medicine, Humans, Knee, Muscle Strength, Muscle, Skeletal, Science & Technology, Neurosciences, 1103 Clinical Sciences, 030229 sport sciences, 020601 biomedical engineering, MODEL, Orthopedics, MUSCLE-ACTIVITY, Physical therapy, Muscle strength, Neurosciences & Neurology, JOINT MOMENTS, human activities, Sport Sciences, ANTERIOR CRUCIATE LIGAMENT
Abstract: We explored the tibiofemoral contact forces and the relative contributions of muscles and external loads to those contact forces during various gait tasks. Second, we assessed the relationships between external gait measures and contact forces. A calibrated electromyography-driven neuromusculoskeletal model estimated the tibiofemoral contact forces during walking (1.44 ± 0.22 m s−1), running (4.38 ± 0.42 m s−1) and sidestepping (3.58 ± 0.50 m s−1) in healthy adults (n = 60, 27.3 ± 5.4 years, 1.75 ± 0.11 m, and 69.8 ± 14.0 kg). Contact forces increased from walking (∼1–2.8 BW) to running (∼3–8 BW), sidestepping had largest maximum total (8.47 ± 1.57 BW) and lateral contact forces (4.3 ± 1.05 BW), while running had largest maximum medial contact forces (5.1 ± 0.95 BW). Relative muscle contributions increased across gait tasks (up to 80–90% of medial contact forces), and peaked during running for lateral contact forces (∼90%). Knee adduction moment (KAM) had weak relationships with tibiofemoral contact forces (all R2 < 0.36) and the relationships were gait task-specific. Step-wise regression of multiple external gait measures strengthened relationships (0.20 < Radj2 < 0.78), but were variable across gait tasks. Step-wise regression equations from a particular gait task (e.g. walking) produced large errors when applied to a different gait task (e.g. running or sidestepping). Muscles well stabilized the knee, increasing their role in stabilization from walking to running to sidestepping. KAM was a poor predictor of medial contact force and load distributions. Step-wise regression models results suggest the relationships between external gait measures and contact forces cannot be generalized across tasks. Neuromusculoskeletal modelling may be required to examine tibiofemoral contact forces and role of muscle in knee stabilization across gait tasks.
Published: 2015

23. A recent bottleneck of Y chromosome diversity coincides with a global change in culture

Author: Sardana A. Fedorova, Ene Metspalu, Anne-Mai Ilumäe, Siiri Rootsi, Lisenka E.L.M. Vissers, François-Xavier Ricaut, Tatiana M. Karafet, David M. Lambert, Richard Villems, Elza Khusnutdinova, Denis Pierron, Daria V. Lichman, Pradiptajati Kusuma, Shahlo Turdikulova, Alena Kushniarevich, Boris Malyarchuk, Anders Eriksson, Bayazit Yunusbayev, Olga Utevska, Ludmila P. Osipova, Christina A. Eichstaedt, Monika Karmin, S. S. Litvinov, Knut Johnsen, Joseph Wee Tien Seng, Reedik Mägi, Alexia Cardona, Oleg Balanovsky, Dragan Primorac, Dilbar Dalimova, Pagbajabyn Nymadawa, Krishna R. Veeramah, Andrea Manica, Rita Khusainova, I. M. Khidiyatova, Michael F. Hammer, Kuvat T. Momynaliev, Sarah A. Tishkoff, Toomas Kivisild, Michael C. Westaway, Zhaxylyk Sabitov, Tarmo Puurand, S M Abdullah, Lejla Kovacevic, Levon Yepiskoposyan, Chris Tyler-Smith, Mario Mitt, Rane Willerslev, Mark G. Thomas, Qasim Ayub, Gazi Nurun Nahar Sultana, Jainagul Isakova, Christian Gilissen, Kristiina Tambets, Craig Muller, Gyaneshwer Chaubey, Thorfinn Sand Korneliussen, Miroslava Derenko, Farida Akhatova, V. L. Akhmetova, Joris A. Veltman, Ulvi Gerst Talas, Hovhannes Sahakyan, Maru Mormina, L. A. Atramentova, Andrea Bamberg Migliano, Vedrana Škaro, Georgi Hudjashov, N. N. Trofimova, Rasmus Nielsen, Mari Järve, Luca Pagani, George Andriadze, Evelin Mihailov, Lauri Saag, Michael DeGiorgio, Mikk Eelmets, Harilanto Razafindrazaka, Irina Evseeva, Murray P. Cox, Elvira Pocheshkhova, Nikolay A. Barashkov, Eva Liis Loogväli, Neil Bradman, Joseph Lachance, Grigor Zoraqi, Eske Willerslev, Melissa A. Wilson Sayres, Elena Balanovska, Fernando L. Mendez, Peter A. Underhill, Doron M. Behar, Mário Vicente, Maido Remm, Mait Metspalu, Yali Xue, Florian Clemente, Andres Metspalu, Zuzana Faltyskova, Damir Marjanović, Dept Evolutionary Biol, University of Tartu, Leverhulme Centre for Human Evolutionary Studies University of Cambridge, University of Cambridge [UK] (CAM), Human Evolution, The Wellcome Trust Sanger Institute [Cambridge], University of Pennsylvania, Human Genetics, Centre National de la Recherche Scientifique (CNRS), Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Environmental Futures Research Institute, Griffith University [Brisbane], Institute of Molecular Biology and Medicine, International Network for the Sequencing of resPIRratory vIrusEs (INSPIRE), Department of Oncology, Radboud University Medical Center [Nijmegen], The Estonian Genome Center, Swedish Institute of Space Physics [Uppsala] (IRF), Marketing Department, Institute of Cytology and Genetics, Russian Academy of Sciences [Moscow] (RAS), Russian Academy of Medical Sciences, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], Wellcome Trust Genome Campus, Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Section for GeoGenetics, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Dept Integrat Biol, UMR 6578 : Anthropologie Bio-Culturelle (UAABC), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Université Tartu, University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)
Subjects: Male, Most recent common ancestor, Population, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, bottleneck, Y chromosome diversity, global change in culture, Human genetic variation, Biology, DNA, Mitochondrial, Haplogroup, Bottleneck, Evolution, Molecular, 03 medical and health sciences, Genetics, Humans, education, Phylogeny, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Chromosomes, Human, Y, Base Sequence, Models, Genetic, Research, Racial Groups, 030305 genetics & heredity, Haplotype, Genetic Variation, Sequence Analysis, DNA, Genetics, Population, Ancient DNA, Haplotypes, Evolutionary biology, Biological dispersal
Abstract: It is commonly thought that human genetic diversity in non-African populations was primarily shaped by a recent out-of-Africa dispersal. Here we present a large geographical Y chromosome study using 459 high coverage sequences, including 302 newly reported here. We date the Y chromosomal Most Recent Common Ancestor (MRCA) in Africa at 254 (95% CI 192- 307) kya and differentiation of African and non-African lineages 52-121 kya. The age estimates for major non-African founder haplogroups cluster closely in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. We find that the highest basal Y chromosome diversity outside Africa has been preserved in South and Southeast Asians while extant Y chromosome diversity in Europe and the Near East stems from a small number of mid-Holocene founders. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck, followed by a fast recovery in Old World populations dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
Published: 2015

24. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

Author: Josep M. Llovet, Vincenzo Mazzaferro, Clément Meiller, Augusto Villanueva, Ludmil B. Alexandrov, Alexis Laurent, Eric Letouzé, Frédéric Soysouvanh, Kornelius Schulze, Sandra Rebouissou, Sandrine Imbeaud, Laura Pelletier, Jean-Charles Nault, Jayendra Shinde, Anna Line Calatayud, Jessica Zucman-Rossi, Michael R. Stratton, Charles Balabaud, Julien Calderaro, Jean-Frédéric Blanc, Paulette Bioulac-Sage, Gabrielle Couchy, Fabien Calvo, Roser Pinyol, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Wellcome Trust Sanger Institute [Cambridge], Theoretical Division [LANL], Los Alamos National Laboratory (LANL), Assistance Publique-Hôpitaux de Paris, Department of Pathology, Centre hospitalier universitaire Henri Mondor, F-94000 Créteil, France, Hepatocellular Carcinoma Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group Barcelona, Catalonia, Spain, Inserm, UMR-1053, Université de Bordeaux, Bordeaux, F-33076, France, Assistance Publique-Hôpitaux de Paris, Department of Digestive and Hepatobiliary Surgery, Centre hospitalier universitaire Henri Mondor, F-94000 Créteil, France, Inserm, UMR-955, F-94000 Créteil, France, Centre hospitalier universitaire de Bordeaux, Department of Hepatology, Hôpital Saint-André, Bordeaux, F-33076, France, Department of Liver Surgery and Transplant, Fondazione Istituto Tumori, via Venezian 1, 20133 Milan, Italy, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaires Paris – Seine Saint-Denis, Site Jean Verdier, Pôle d’Activité Cancérologique Spécialisée, Service d’Hépatologie, F-93143 Bondy, France, Centre hospitalier universitaire de Bordeaux, Pellegrin Hospital, Department of Pathology, Bordeaux, F-33076, France, Institució Catalana de Recerca i Estudis Avançats (ICREA), Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou, F-75015 Paris, France, Schulze, Kornelius, Université Paris 13 (UP13) - Université Paris Diderot - Paris 7 (UPD7) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom, Mount Sinai Liver Cancer Program (Division of Liver Diseases), Mount Sinai School of Medicine, New York, USA, and Institució Catalana de Recerca i Estudis Avançats, Barcelona. Catalonia, Spain
Subjects: Male, Carcinoma, Hepatocellular, Lactams, Macrocyclic, medicine.medical_treatment, DNA Mutational Analysis, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, medicine.disease_cause, Bioinformatics, Article, Targeted therapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, CDKN2A, Cell Line, Tumor, Benzoquinones, NAD(P)H Dehydrogenase (Quinone), Genetics, medicine, Humans, Exome, HSP90 Heat-Shock Proteins, Molecular Targeted Therapy, Genetic Association Studies, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Aged, Sequence Deletion, Hepatitis B virus, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Liver Neoplasms, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Hepatocellular carcinoma, Cancer research, Female, Liver cancer
Abstract: Genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. Analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereas FGF3, FGF4, FGF19 or CCND1 amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)-approved drugs. In conclusion, we identified risk factor-specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.
Published: 2015

25. Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells

Author: Teunis B. H. Geijtenbeek, Gianfranco Pancino, Günter Weiss, Olivier Lambotte, Paul Kellam, Ralf Gallasch, Cornelia Lass-Flörl, Doris Wilflingseder, Zlatko Trajanoski, Hubert Hackl, Andrea Schroll, Wilfried Posch, Dan Frampton, Asier Sáez-Cirión, Laurence Weiss, Guibert, Marie-Genevieve, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University College of London [London] (UCL), Wellcome Trust Genome Campus, Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), This work was supported by the Austrian Science Fund (grants FWF P22165 and P24598 to D. W., SFB 021 to Z. T., and P25389 to W. P.), the Oesterreichische Nationalbank Anniversary Fund (project 14875 to W. P.), and the Agence Nationale de la Recherche Contre le SIDA et les Hépatites Virales (to A. S.-C.)., Amsterdam institute for Infection and Immunity, Infectious diseases, Experimental Immunology, Innsbruck Medical University [Austria] (IMU), Institut Pasteur [Paris], and HIV, Inflammation et persistance
Subjects: Adult, Male, opsonization, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, CD11c, chemical and pharmacologic phenomena, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, medicine, Immunology and Allergy, Humans, complement, Antigens, 030304 developmental biology, 0303 health sciences, CD11b Antigen, biology, Follicular dendritic cells, CD11b, Cell Differentiation, Complement System Proteins, Dendritic Cells, Middle Aged, MAPK, 3. Good health, CD11c Antigen, Antibody opsonization, Infectious Diseases, Cytokine, Integrin alpha M, Immunology, biology.protein, HIV-1, Th17 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Th17, Ex vivo, 030215 immunology
Abstract: International audience; Early on in human immunodeficiency virus (HIV) type 1 infection, gut T-helper (Th) 17 cells are massively depleted leading eventually to compromised intestinal barrier function and excessive immune activation. In contrast, the functional Th17 cell compartment of the gut is well-maintained in nonpathogenic simian immunodeficiency virus infection as well as HIV-1 long-term nonprogressors. Here, we show that dendritic cells (DCs) loaded with HIV-1 bearing high surface complement levels after incubation in plasma from HIV-infected individuals secreted significantly higher concentrations of Th17-polarizing cytokines than DCs exposed to nonopsonized HIV-1. The enhanced Th17-polarizing capacity of in vitro-generated and BDCA-1(+) DCs directly isolated from blood was linked to activation of ERK. In addition, C3a produced from DCs exposed to complement-opsonized HIV was associated with the higher Th17 polarization. Our in vitro and ex vivo data, therefore, indicate that complement opsonization of HIV-1 strengthens DC-mediated antiviral immune functions by simultaneously triggering Th17 expansion and intrinsic C3 formation via DC activation.
Published: 2015

26. Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

Author: Doris Lechner, Miriam Capri, Stefan Böhringer, Stefan Schreiber, Gonneke Willemsen, Paolo Garagnani, Irene Maeve Rea, Andres Metspalu, Palmi V. Jonsson, Thomas B. L. Kirkwood, Lene Christiansen, Fernando Rivadeneira, Giuseppina Rose, J. Wouter Jukema, Serena Dato, Owen A. Ross, Almut Nebel, Cornelia M. van Duijn, Gary Saunders, Bernard Jeune, David J. Stott, Jeanine J. Houwing-Duistermaat, A. Murphy, Anton J. M. de Craen, Friederike Flachsbart, Karen Andersen-Ranberg, Albert Hofman, Ian Ford, Ellen A. Nohr, Giuseppe Passarino, Krista Fischer, Elisa Cevenini, Carmen Martin-Ruiz, Jutta Gampe, Iris Postmus, Christopher P. Nelson, Stefano Salvioli, Alberto Montesanto, Mark Lathrop, Marianne Nygaard, Marie E. Breen, Jennifer Harrow, Hae-Won Uh, Erik B. van den Akker, Thorkild I. A. Sørensen, André G. Uitterlinden, Alexander Viktorin, Bastiaan T. Heijmans, Susan E. McNerlan, Quinta Helmer, Naveed Sattar, Claudio Franceschi, Eco J. C. de Geus, E. Mihailov, Jouke-Jan Hottenga, Qihua Tan, Kari Stefansson, Yoichiro Kamatani, Paolina Crocco, Henning Tiemeier, Stella Trompet, Patrik K. E. Magnusson, Marian Beekman, Riin Tamm, Amke Caliebe, Maris Alver, Femke-Anouska Heinsen, Pilar Galan, Daníel F. Guðbjartsson, Joris Deelen, Linda Broer, Ruud van der Breggen, Kristin L. Ayers, Anna M. Bennet, Dorret I. Boomsma, P. Eline Slagboom, Kaare Christensen, Diana van Heemst, Joanna Collerton, Karen Davies, Rudi G. J. Westendorp, Hélène Blanché, Lavinia Paternoster, Nilesh J. Samani, Hreinn Stefansson, Simon P. Mooijaart, Heather J. Cordell, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), LeidenUniversity Medical Centre, Department of Epidemiology, The Netherlands Cancer Institute, Institute of Genetic Medicine, Newcastle University [Newcastle], National Institute of Public Health, University of Southern Denmark (SDU), Department of Clinical Genetics, Odense University Hospital, Fondation Jean Dausset - Centre d’Étude du Polymorphisme Humain, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Tartu, Institute of Molecular and Cell Biology, Department of Gerontology and Geriatrics, Leiden University Medical Center (LUMC), deCODE genetics [Reykjavik], Christian-Albrechts University of Kiel, University of Calabria, Delft University of Technology (TU Delft), Department of Cardiovascular Sciences, Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospitals Leicester, Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], School of Medicine, Dentistry and Biomedical Sciences [Belfast], Queen's University [Belfast] (QUB), University of Iowa [Iowa City], DIMES: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Institute for Ageing and Health, University of Glasgow, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), EMGO Institute for Health and Care Research, VU University Amsterdam Medical Center, Landspitali National University Hospital of Iceland, University of Iceland, McGill University = Université McGill [Montréal, Canada], Genome Quebec Innovation Centre, Institut de Génomique, Belfast Health and Social Care Trust, Estonian Biocentre, Partenaires INRAE, Aarhus University [Aarhus], School of Social and Community Medicine, Erasmus University Rotterdam, Mayo Clinic, BHF Glasgow Cardiovascular Research Centre, University Medical Center Schleswig-Holstein, Institute of Cardiovascular and Medical Sciences, Sophia Children's Hospital, 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), Augustinus Foundation, Avera Institute for Human Genetics (AIHG), AXA Research Fund, Belfast City Hospital Trust Fund, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI -NL) [184.021.007], Biotechnology and Biological Sciences Research Council (BBSRC), Bristol-Myers Squibb, Center for Inherited Disease Research (CIDR), Centre for Medical Systems Biology (CMSB), CERA Foundation, Commissariat a L'Energie Atomique (CEA)-Centre National de Genotypage (CNG), Danish Agency for Science, Technology and Innovation (DASTI)/The Danish Council for Independent Research (DCIR) [11-107308], Danish National Research Foundation (DNRF), Department of Health and Social Services (Northern Ireland), DFG-Cluster of Excellence 'Inflammation at Interfaces', Dunhill Medical Trust [R124/0509], Egmont Foundation, Estonian Science Foundation [7859], Estonian Government [SF0180142s08], European Research Council (ERC) [230374], European Science Foundation (ESF) [EU/QLRT-2001-01254], European Union [FP5-QLK6-CY-2001-00128, FP6-LIFESCIHEALTH-36894, FP6-LSH M-CT-2004-503270, FP7-HEALTH-2007-B-223004, FP7-HEALTH-F4-2007-201413, FP7-HEALTH-F4-2008-202047, FP7-HEALTH-2009-single-stage-242244, FP7-HEALTH-2010-two-stage-259679], Fondation Caisse d'Epargne Rhone-Alpes Lyon CERAL, Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health (NIMH) [MH081802], GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254], Guy's & St Thomas' NHS Foundation Trust, Health Foundation, Heart and Lung foundation [20070481], Innovation-Oriented Research Program on Genomics (SenterNovem) [IGE05007], Institut National de la Recherche Agronomique (INRA), Institut National de la Sante et de la Recherche Medicale (INSERM), King's College London, Medical Research Council (MRC) [G0500997, G0601333], Ministere de l'Enseignement superieur et de la Recherche (MESR), National Institutes of Health (NIH)/National Institute of Aging (NIA) [P01AG08761, R01D0042157-01A, U01DK066134], National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre, NBIC BioAssist [NWO-NBIC/BioAssist/RK/2008.024], Netherlands Consortium for Healthy Ageing (NCHA) [050-060-810], Netherlands Genomics Initiative (NGI), Netherlands Heart Foundation (NHF) [2001 D 032], Netherlands Organization for Scientific Research (NWO, MagW/ZonMW) [904-61-090, 904-61-193, 480-04-004, 400-05-717, Spinozapremie 56-464-14192, 175.010.2005.011, 911-03-012, 985-10-002, Addiction-31160008, Middelg-root-911-09-032], Netspar - Living longer for a good health, NHS North of Tyne (Newcastle Primary Care Trust), Pharmacy Foundation, Regione Autonoma della Sardegna, Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06], Swedish Research Council [M-2005-1112], Tampere University Hospital and Academy of Finland, Danish Interdisciplinary Research Council, Health Foundation (Helsefonden), Ministry for Higher Education, National Program for Research Infrastructure [09-063256], March of Dimes Birth Defects Foundation, Swedish Foundation for Strategic Research (SSF), Unilever Discover Colworth, Universite Paris 13, University of Tartu [SP1GVAR-ENG], Velux Foundation, VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA), Wellcome Trust [084762, 085475, 087436], IDEAL [FP7-HEALTH-2010-two-stage-259679], Research and Education into Ageing-0153, European Regional Development Fund, Deelen J, Beekman M, Uh HW, Broer L, Ayers KL, Tan Q, Kamatani Y, Bennet AM, Tamm R, Trompet S, Guðbjartsson DF, Flachsbart F, Rose G, Viktorin A, Fischer K, Nygaard M, Cordell HJ, Crocco P, van den Akker EB, Böhringer S, Helmer Q, Nelson CP, Saunders GI, Alver M, Andersen-Ranberg K, Breen ME, van der Breggen R, Caliebe A, Capri M, Cevenini E, Collerton JC, Dato S, Davies K, Ford I, Gampe J, Garagnani P, de Geus EJ, Harrow J, van Heemst D, Heijmans BT, Heinsen FA, Hottenga JJ, Hofman A, Jeune B, Jonsson PV, Lathrop M, Lechner D, Martin-Ruiz C, McNerlan SE, Mihailov E, Montesanto A, Mooijaart SP, Murphy A, Nohr EA, Paternoster L, Postmus I, Rivadeneira F, Ross OA, Salvioli S, Sattar N, Schreiber S, Stefánsson H, Stott DJ, Tiemeier H, Uitterlinden AG, Westendorp RG, Willemsen G, Samani NJ, Galan P, Sørensen TI, Boomsma DI, Jukema JW, Rea IM, Passarino G, de Craen AJ, Christensen K, Nebel A, Stefánsson K, Metspalu A, Magnusson P, Blanché H, Christiansen L, Kirkwood TB, van Duijn CM, Franceschi C, Houwing-Duistermaat JJ, Slagboom PE., Leiden Univ, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands [ 2 ] Leiden Univ, Netherlands Consortium Healthy Ageing, NL-2300 RC Leiden, Netherlands [ 3 ] Leiden Univ, Dept Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands [ 4 ] Leiden Univ, Dept Cardiol, NL-2300 RC Leiden, Netherlands [ 5 ] Leiden Univ, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands [ 6 ] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands [ 7 ] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands [ 8 ] Newcastle Univ, Int Ctr Life, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England [ 9 ] Univ So Denmark, Inst Publ Hlth, DK-5000 Odense C, Denmark [ 10 ] Univ So Denmark, Inst Clin Res, Dept Gynecol & Obstet, DK-5000 Odense C, Denmark [ 11 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark [ 12 ] Odense Univ Hosp, Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark [ 13 ] Fdn Jean Dausset CEPH, F-75010 Paris, France [ 14 ] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden [ 15 ] Univ Tartu, Estonian Genome Ctr, Tartu 51010, Estonia [ 16 ] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia [ 17 ] deCODE Genet, Populat Gen, IS-101 Reykjavik, Iceland [ 18 ] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany [ 19 ] Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany [ 20 ] Univ Calabria, Dept Biol Ecol & Earth Sci, I-87036 Arcavacata Di Rende, Italy [ 21 ] Delft Univ Technol, Delft Bioinformat Lab, NL-2600 GA Delft, Netherlands [ 22 ] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England [ 23 ] Glenfield Hosp, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester LE3 9QP, Leics, England [ 24 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England [ 25 ] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland [ 26 ] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA [ 27 ] Univ Bologna, Dept Expt Diagnost & Specialty Med, I-40126 Bologna, Italy [ 28 ] Univ Bologna, Interdepartmental Ctr L Galvani, I-40126 Bologna, Italy [ 29 ] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England [ 30 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland [ 31 ] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland [ 32 ] Max Planck Inst Demograf Forsch, Lab Stat Demog, D-18057 Rostock, Germany [ 33 ] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands [ 34 ] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands [ 35 ] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland [ 36 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland [ 37 ] CEA, Inst Genom, F-91057 Evry, France [ 38 ] McGill Univ, Montreal, PQ H3G 1A4, Canada [ 39 ] Genome Quebec Innovat Ctr, Montreal, PQ H3G 1A4, Canada [ 40 ] Belfast Hlth & Social Care Trust, Cytogenet Lab, Belfast BT8 8BH, Antrim, North Ireland [ 41 ] Estonian Bioctr, EE-51010 Tartu, Estonia [ 42 ] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark [ 43 ] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England [ 44 ] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA [ 45 ] Univ Glasgow, Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland [ 46 ] Univ Kiel, PopGen Biobank, D-24105 Kiel, Germany [ 47 ] Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany [ 48 ] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CA Rotterdam, Netherlands [ 49 ] Univ Paris 04, UREN, U557, INSERM, F-93017 Bobigny, France [ 50 ] U1125 Inra, F-93017 Bobigny, France [ 51 ] Cnam, F-93017 Bobigny, France [ 52 ] Univ Paris 13, CRNH IdF, F-93017 Bobigny, France [ 53 ] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr, DK-2200 Copenhagen N, Denmark [ 54 ] Inst Prevent Med, DK-2000 Copenhagen, Denmark [ 55 ] Frederiksberg Univ Hosp, DK-2000 Copenhagen, Denmark [ 56 ] Interuniv Cardiol Inst Netherlands, NL-3501 DG Utrecht, Netherlands [ 57 ] Bellaria Hosp, IRCCS Inst Neurol Sci, I-40139 Bologna, Italy [ 58 ] CNR, ISOF, I-40129 Bologna, Italy, Epidemiology, Surgery, Internal Medicine, Child and Adolescent Psychiatry / Psychology, ProdInra, Migration, Vrije Universiteit Amsterdam [Amsterdam] (VU), 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), VU University Amsterdam, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Male, Netherlands Twin Register (NTR), Disease/genetics, Lífslíkur, Longevity/genetics, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Genetic Linkage, Genome-wide association study, 0302 clinical medicine, Prospective Studies, Genetics (clinical), Genetics, Aged, 80 and over, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Association Studies Articles, Age Factors, Chromosome Mapping, Genetic Loci/physiology, General Medicine, 3. Good health, Europe, Phenotype, Cardiovascular Diseases, Hypertension, Chromosomes, Human, Pair 5, Female, Human Longevity, genetics, meta-analysis, Aging/genetics, Cardiology and Cardiovascular Medicine, HUMAN AGING, Longevity, European Continental Ancestry Group, Population, HUMAN GENETICS, Single-nucleotide polymorphism, Locus (genetics), Biology, FAMILIAL LONGEVITY, White People, 03 medical and health sciences, Gene mapping, SDG 3 - Good Health and Well-being, Cardiovascular Diseases/genetics, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Allele, education, Molecular Biology, Aged, 030304 developmental biology, Genetic association, Öldrun, Genome, Human, Arfgengi, Minor allele frequency, Ageing, Genetic Loci, Chromosomes, Human, Pair 19, Hypertension/genetics, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract: To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. The genetic contribution to the variation in human lifespan is ∼ 25%. Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality. We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16 121 younger controls (
Published: 2014

27. Large scale variation in DNA copy number in chicken breeds

Author: Shurnevia Strickland, Richard P. M. A. Crooijmans, Mark Fife, Richard Redon, Martien A. M. Groenen, Peter K. Kaiser, Tomas W Fitzgerald, Hans H. Cheng, Animal Breeding and Genomics Centre, Wageningen University and Research [Wageningen] (WUR), Genetics and Genomics group, Compton Laboratory, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Department of Animal & Food Sciences, University of Delaware [Newark], Avian Disease and Oncology Laboratory, 4279 E Mount Hope Road, The Roslin Institute, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Biotechnology and Biological Sciences Research Council (BBSRC), Unité de recherche de l'institut du thorax (ITX-lab), and BMC, Ed.
Subjects: Male, Genetic Linkage, Breeding, Genome, feather, Cluster Analysis, Copy-number variation, genes, 2. Zero hunger, Genetics, Comparative Genomic Hybridization, 0303 health sciences, 04 agricultural and veterinary sciences, Chicken, Line-specific CNVs, loci, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Research Article, Biotechnology, DNA Copy Number Variations, mareks-disease, Single-nucleotide polymorphism, Biology, Animal Breeding and Genomics, Structural variation, resistance, 03 medical and health sciences, aCGH, pcr, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetic variation, evolution, human genome, map, Animals, Fokkerij en Genomica, 030304 developmental biology, Copy number variation, 0402 animal and dairy science, Inter-specific CNVs, structural variation, Computational Biology, 040201 dairy & animal science, Genes, WIAS, Human genome, Chickens, Reference genome, Comparative genomic hybridization
Abstract: International audience; BACKGROUND: Detecting genetic variation is a critical step in elucidating the molecular mechanisms underlying phenotypic diversity. Until recently, such detection has mostly focused on single nucleotide polymorphisms (SNPs) because of the ease in screening complete genomes. Another type of variant, copy number variation (CNV), is emerging as a significant contributor to phenotypic variation in many species. Here we describe a genome-wide CNV study using array comparative genomic hybridization (aCGH) in a wide variety of chicken breeds. RESULTS: We identified 3,154 CNVs, grouped into 1,556 CNV regions (CNVRs). Thirty percent of the CNVs were detected in at least 2 individuals. The average size of the CNVs detected was 46.3 kb with the largest CNV, located on GGAZ, being 4.3 Mb. Approximately 75% of the CNVs are copy number losses relatively to the Red Jungle Fowl reference genome. The genome coverage of CNVRs in this study is 60 Mb, which represents almost 5.4% of the chicken genome. In particular large gene families such as the keratin gene family and the MHC show extensive CNV. CONCLUSIONS: A relative large group of the CNVs are line-specific, several of which were previously shown to be related to the causative mutation for a number of phenotypic variants. The chance that inter-specific CNVs fall into CNVRs detected in chicken is related to the evolutionary distance between the species. Our results provide a valuable resource for the study of genetic and phenotypic variation in this phenotypically diverse species.
Published: 2013

28. Genome-wide diversity in the levant reveals recent structuring by culture

Author: Daniel E. Platt, Laura R. Botigué, R. Spencer Wells, Priya Moorjani, Dominique Gauguier, Chris Tyler-Smith, Pierre Zalloua, Sonia Youhanna, Nick Patterson, David Comas, Jaume Bertranpetit, Elizabeth Matisoo-Smith, Marc Haber, David F. Soria-Hernanz, Williams, Scott M, Institut de Biologia Evolutiva (CSIC-UPF), Lebanese American University ( LAU ), Wellcome Trust Centre for Human Genetics, University of Oxford [Oxford], Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston] ( MGH ) -Massachusetts Institute of Technology ( MIT ), Harvard Medical School [Boston] ( HMS ), Universitat Pompeu Fabra [Barcelona], Bioinformatics and Pattern Discovery, IBM T. J. Watson Research Centre, Allan Wilson Center for Molecular Ecology and Evolution, University of Auckland [Auckland], National Geographic Society, Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Harvard School of Public Health, Lebanese American University (LAU), The Wellcome Trust Centre for Human Genetics [Oxford], Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Universitat Pompeu Fabra [Barcelona] (UPF), University of Auckland [Auckland]-Massey University-University of Canterbury [Christchurch]-University of Otago [Dunedin, Nouvelle-Zélande], The Wellcome Trust Sanger Institute [Cambridge], University of Oxford, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lebanese American University, Wellcome Trust, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and HAL UPMC, Gestionnaire
Subjects: Cancer Research, [SDV.GEN] Life Sciences [q-bio]/Genetics, 0302 clinical medicine, Effective population size, Peninsula, ADN mitocondrial -- Genètica, Ethnicity, Glacial period, Genetics (clinical), Phylogeny, African Continental Ancestry Group, Genetics, 0303 health sciences, education.field_of_study, Middle East, geography.geographical_feature_category, Genètica de poblacions, Genome, Paleogenetics, Gene Pool, Blacks, Mitochondrial, Archaeology, Ethnology, Genetic isolate, Research Article, Human, Gene Flow, lcsh:QH426-470, Population, European Continental Ancestry Group, Black People, Ethnic Groups, Biology, DNA, Mitochondrial, White People, Chromosomes, 03 medical and health sciences, Genetic drift, Effective Population Size, Cultural Evolution, Humans, education, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, geography, Cromosomes humans, [SDV.GEN]Life Sciences [q-bio]/Genetics, Chromosomes, Human, Y, Genome, Human, Whites, Genetic Drift, Human Genome, Genetic Variation, DNA, lcsh:Genetics, Genetics, Population, Haplotypes, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, Population Genetics, Developmental Biology
Abstract: The Levant is a region in the Near East with an impressive record of continuous human existence and major cultural developments since the Paleolithic period. Genetic and archeological studies present solid evidence placing the Middle East and the Arabian Peninsula as the first stepping-stone outside Africa. There is, however, little understanding of demographic changes in the Middle East, particularly the Levant, after the first Out-of-Africa expansion and how the Levantine peoples relate genetically to each other and to their neighbors. In this study we analyze more than 500,000 genome-wide SNPs in 1,341 new samples from the Levant and compare them to samples from 48 populations worldwide. Our results show recent genetic stratifications in the Levant are driven by the religious affiliations of the populations within the region. Cultural changes within the last two millennia appear to have facilitated/maintained admixture between culturally similar populations from the Levant, Arabian Peninsula, and Africa. The same cultural changes seem to have resulted in genetic isolation of other groups by limiting admixture with culturally different neighboring populations. Consequently, Levant populations today fall into two main groups: one sharing more genetic characteristics with modern-day Europeans and Central Asians, and the other with closer genetic affinities to other Middle Easterners and Africans. Finally, we identify a putative Levantine ancestral component that diverged from other Middle Easterners ~23,700-15,500 years ago during the last glacial period, and diverged from Europeans ~15,900-9,100 years ago between the last glacial warming and the start of the Neolithic. © 2013 Haber et al., This study was partly supported by the Lebanese American University and the National Geographic Society (The Genographic Project). CT-S was supported by grant number 098051 from The Wellcome Trust., Haber, Marc et al.
Published: 2013

29. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Author: Thibaut Jombart, Nicholas R. Thomson, David M. Wagner, Jacques Ravel, Giovanna Morelli, Philippe Roumagnac, Camila J. Mazzoni, Yujun Cui, Lila Rahalison, Yanjun Li, Mark Eppinger, Barica Kusecek, Raphaël Leblois, Paul Keim, Ruifu Yang, Mark Achtman, Thierry Wirth, Amy J. Vogler, Jeannine M. Petersen, Mirjam Feldkamp, Peter Lichtner, Yajun Song, Elisabeth Carniel, Francois Balloux, Department of Molecular Biology [MPIIB Berlin], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Department of Microbiology and Environmental Research Institute (Cork, Ireland), University College Cork (UCC), Institute for Genome Sciences, University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Biologie et Génétique des Interactions Plante-Parasite (UMR BGPI), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Department of Biological Sciences [Flagstaff], Northern Arizona University [Flagstaff], The Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Medical Research Council, Centre for Outbreak Analysis and Modelling (MRC), Imperial College Faculty of Medicine, Département Systématique et Évolution, Muséum national d'Histoire naturelle (MNHN), Institute of Human Genetics, German Research Center for Environmental Health, Laboratoire Central de la Peste (CNR), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Pathogen Genomics Division, The Translational Genomics Research Institute (TGen), Yersinia, Institut Pasteur [Paris], We gratefully acknowledge technical assistance by R. Nera and A. Doyle and helpful comments from A. Rambaut and D. Falush. Support was provided by grants from the German Army Medical Corps (MSAB15A013) and the Science Foundation of Ireland (05/FE1/B882) to M.A., the National Key Program for Infectious Diseases of China (2008ZX10004-009) and the State Key Development Program for Basic Research of China (2009CB522600) to R.Y. and the US Department of Homeland Security (NBCH2070001, SHQDC-08-C00158) and US National Institutes of Health (AI065359) to P.K. and D.M.W. Whole genome sequencing of Y. pestis strains IP275, MG05-1020 and UG05-045 was supported by federal funds from the National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Department of Health and Human Services (N01 AI-30071), and sequencing of IP674 was supported by funding for Sanger Institute Pathogen Genomics by the Wellcome Trust. Genomic DNA of Y. pestis MG05-1020 was kindly provided by S. Bearden and M. Schriefer (Centers for Disease Control and Prevention, Fort Collins, Colorado, USA)., Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Helmholtz Zentrum München = German Research Center for Environmental Health, and Institut Pasteur [Paris] (IP)
Subjects: Phylogénie, MESH: Sequence Analysis, DNA, Yersinia pestis, [SDV]Life Sciences [q-bio], MESH: Yersinia pestis, Genomic comparisons, phylogeography, Biology, MESH: Genome, Bacterial, Polymorphism, Single Nucleotide, Genome, MESH: Plague, Article, DNA sequencing, 03 medical and health sciences, Variation génétique, Maladie de l'homme, epidemic spread, Genetics, Typing, MESH: Genetic Variation, neutral evolution, MESH: Phylogeny, Phylogeny, 030304 developmental biology, Plague, 0303 health sciences, Génome, Phylogenetic tree, 030306 microbiology, MESH: Polymorphism, Single Nucleotide, Genetic Variation, Microevolution, Sequence Analysis, DNA, biology.organism_classification, 3. Good health, Maximum parsimony, QR, SNP typing, Phylogenetic diversity, S50 - Santé humaine, Genome, Bacterial
Abstract: International audience; Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.
Published: 2010

30. Design of a high density SNP genotyping assay in the pig using SNPs identified and characterized by next generation sequencing technology

Author: Patrick Dehais, Andy Law, A. M. Ramos, Richard Clark, Denis Milan, Richard P. M. A. Crooijmans, Jakob Hedegaard, Nabeel A. Affara, Robert D. Schnabel, Gary A. Rohrer, Curt P. Van Tassell, Zhi-Liang Hu, Max F. Rothschild, Lawrence B. Schook, Christian Bendixen, Hendrik-Jan Megens, Timothy P. L. Smith, Hindrik H. D. Kerstens, Andreia J. Amaral, Carol Churcher, Alan Archibald, Jonathan E. Beever, D. J. Nonneman, Jeremy F. Taylor, Martien A. M. Groenen, Ralph T Wiedmann, Mark Hansen, Groenen, Martien A.M., Animal Breeding and Genomics Centre, Wageningen University and Research [Wageningen] (WUR), Department of Pathology, University of Cambridge [UK] (CAM), University of Edinburgh, Institute for Genomic Biology, University of Illinois System, Faculty of Agricultural Sciences, Aarhus University [Aarhus], The Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], 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, Illumina, Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University (ISU), United States Department of Agriculture (USDA), Division of Animal Sciences, University of Missouri [Columbia] (Mizzou), and University of Missouri System-University of Missouri System
Subjects: pig, medicine, Swine, [SDV]Life Sciences [q-bio], Molecular Inversion Probe, Education, Extension, Information and Training (General) [CC000], reviews, 2. Zero hunger, Genetics, 0303 health sciences, education.field_of_study, education, Multidisciplinary, evaluation, methodology, 04 agricultural and veterinary sciences, Tag SNP, SNP genotyping, Professions, snp marker, Medicine, Research Article, Genotype, Genetics and Genomics/Animal Genetics, Science, Population, Single-nucleotide polymorphism, Biology, Practice and Service [CC700], Animal Breeding and Genomics, Polymorphism, Single Nucleotide, methods, 03 medical and health sciences, Species Specificity, Genetics and Genomics/Population Genetics, SNP, Life Science, Animals, porcin, Fokkerij en Genomica, Genetics and Genomics/Genomics, Genotyping, Techniques and Methodology [ZZ900], 030304 developmental biology, medical sciences, literature reviews, 0402 animal and dairy science, Sequence Analysis, DNA, 040201 dairy & animal science, Minor allele frequency, veterinary medicine, WIAS, medical education, techniques
Abstract: BackgroundThe dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay.Methodology/Principal FindingsA total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274.Conclusions/SignificanceOverall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs. Udgivelsesdato: August 5. BackgroundThe dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay.Methodology/Principal FindingsA total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274.Conclusions/SignificanceOverall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs.
Published: 2009

31. 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

32. A genomic history of Aboriginal Australia

Author: Sankar Subramanian, David M. Lambert, Pascale Gerbault, Joe Dortch, Stephan Peischl, Marta Mirazón Lahr, Sturla Ellingvåg, Nicolas Brucato, Anna-Sapfo Malaspinas, Gudjugudju Fourmile, François-Xavier Ricaut, William Pomat, Simon Rasmussen, Mark Stoneking, Tim H. Heupink, Mait Metspalu, Michael C. Westaway, J. Víctor Moreno-Mayar, Shengyu Ni, Aubrey Lynch, Elizabeth Matisoo-Smith, Fernando Racimo, Joanne L. Wright, Anders Albrechtsen, Farhang Aghakhanian, Andrea Manica, Warren Clark, Ivan P. Levkivskyi, Yali Xue, Thomas Wales, Rasmus Nielsen, Andrea Bamberg Migliano, Alexander J. Mentzer, Craig Muller, Laurent Excoffier, Anders Bergström, Irina Pugach, Thomas Mailund, Søren Brunak, Jacob E. Crawford, Richard Durbin, Paula F. Campos, Anders Eriksson, Claire Bowern, George Koki, Enrico Macholdt, Manjinder S. Sandhu, Ashot Margaryan, Les Murgha, Betty Logan, Vitor C. Sousa, Thorfinn Sand Korneliussen, Maude E. Phipps, Jade Yu Cheng, Isabel Alves, Stephan Schiffels, Eske Willerslev, Colleen Ma Run Wall, Robert Foley, Georgios Athanasiadis, Chris Tyler-Smith, Stephen Oppenheimer, Oscar Lao, Mark G. Thomas, Ida Moltke, Darren Injie, Jeffrey D. Wall, Mikkel H. Schierup, Chiara Barbieri, Doc Reynolds, Peter McAllister, Peter Siba, Martin Sikora, Matthew Leavesley, Isabelle Dupanloup, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U901), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Forensic Molecular Biology, ErasmusMC, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Evolutionary Genetics, Environmental Futures Centre, Griffith University [Brisbane], Section of Biostatistics [Copenhagen], Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Institute of Ecology and Evolution, University of Berne, Swedish Institute of Space Physics [Uppsala] (IRF), Institut de Biologia Evolutiva (UPF-CSIC), Human Evolution, The Wellcome Trust Sanger Institute [Cambridge], Human Genetics, Technical University of Denmark [Lyngby] (DTU), Allan Wilson Center for Molecular Ecology and Evolution, University of Auckland [Auckland], Wellcome Trust Ctr Human Genet, University of Oxford [Oxford], University of Tartu, Papua New Guinea Institute of Medical Research, Papua New Guinea of Medical Research, Wellcome Trust Genome Campus, Yale University [New Haven], Bioinformatics Research Center (BiRC), Dept Integrat Biol, Strangeways Research Laboratory, MRC, Zoological Institute - Conservation Biology, University of Bern, Section for GeoGenetics, Globe Institute, Center for Biological Sequence Analysis, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Auckland [Auckland]-Massey University-University of Canterbury [Christchurch]-University of Otago [Dunedin, Nouvelle-Zélande], Papua New Guinea Institute of Medical Research (PNG-IMR), Université Nice Sophia Antipolis (1965 - 2019) (UNS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universität Bern [Bern] (UNIBE), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Oxford, Eriksson, Anders [0000-0003-3436-3726], Durbin, Richard [0000-0002-9130-1006], Manica, Andrea [0000-0003-1895-450X], Foley, Robert [0000-0003-0479-3039], Mirazon Lahr, Marta [0000-0001-5752-5770], Sandhu, Manjinder [0000-0002-2725-142X], Willerslev, Eske [0000-0002-7081-6748], and Apollo - University of Cambridge Repository
Subjects: Gene Flow, 0301 basic medicine, Native Hawaiian or Other Pacific Islander, Neanderthal, Population genetics, Human Migration, Population Dynamics, Population, Population structure, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Datasets as Topic, Tasmania, 03 medical and health sciences, 0302 clinical medicine, biology.animal, Humans, education, Denisovan, History, Ancient, Phylogeny, Language, New Guinea, education.field_of_study, Multidisciplinary, biology, Genome, Human, Human migration, business.industry, Racial Groups, Australia, New guinea, Genomics, biology.organism_classification, Data processing, Genetics, Population, 030104 developmental biology, Geography, Anthropology, Africa, Ethnology, Biological dispersal, Desert Climate, business, 030217 neurology & neurosurgery
Abstract: The population history of Aboriginal Australians remains largely uncharacterised, not least because of a lack of extensive genomic data. We generated high-coverage genomes for 83 geographically diverse Aboriginal Australians (all speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified from each other 25-40 thousand years ago (kya), suggesting early population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all contemporary Aboriginal Australians studied descend from a single founding population that differentiated around 10-32 kya. We infer a population expansion in northeast Australia during the Holocene (past c.10 kya) associated with limited gene flow from this region to the rest of Australia. This is broadly consistent with the spread of the Pama-Nyungan languages and cultural changes taking place across the continent in the mid-Holocene. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 60-100 kya, following a single out of Africa dispersal and subsequent admixture with different archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.
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33. DisProt in 2022: improved quality and accessibility of protein intrinsic disorder annotation

Author: Valentin Iglesias, Vasilis J. Promponas, Alexander Miguel Monzon, Konstantinos D. Tsirigos, Juliet F Nilsson, Attila Mészáros, Samuel Peña-Díaz, Edoardo Salladini, Silvio C. E. Tosatto, Peter Tompa, Zsuzsanna Dosztányi, Zsofia E. Kalman, Norman E. Davey, Christos A. Ouzounis, Nazanin Farahi, Giovanni Minervini, Martín N. Salas, Arne Elofsson, Mátyás Pajkos, Julia Marchetti, Maria Cristina Aspromonte, Elena Papaleo, Sonia Longhi, Juliana Glavina, Anastasia Chasapi, Federica Quaglia, Gabriele Pozzati, Tamás Szaniszló, Rita Pancsa, Damiano Piovesan, András Hatos, Aditi Shenoy, Bálint Mészáros, Suvarna Nadendla, Javier Iserte, Pascale Gaudet, Lucía B. Chemes, Emanuela Leonardi, Jaime Santos, Radoslav Davidovic, Michelle G. Giglio, Gábor Erdős, Eva Schad, Emiliano Maiani, Salvador Ventura, Pedro Pereira, László Dobson, Nevena Veljkovic, Jordi Pujols, Claudio Bassot, Alma Carolina Sanchez Rocha, Veronika Ács, Cristina Marino-Buslje, Erzsébet Fichó, Gustavo Parisi, Sandra Macedo-Ribeiro, Nicolas Palopoli, Luciana Rodriguez Sawicki, Marian Novotný, Tamas Lazar, Matteo Lambrughi, Universita degli Studi di Padova, European Molecular Biology Laboratory [Heidelberg] (EMBL), Research Centre for Natural Sciences, Hungarian Academy of Sciences (MTA), Universidad Nacional de San Martin (UNSAM), Eötvös Loránd University (ELTE), Vrije Universiteit Brussel (VUB), Universitat Autònoma de Barcelona (UAB), Stockholm University, Centre for Research & Technology Hellas, Chester Beatty Laboratories, University of Belgrade [Belgrade], Swiss Institute of Bioinformatics [Genève] (SIB), University of Maryland School of Medicine, University of Maryland System, Fundación Instituto Leloir [Buenos Aires], Pázmány Péter Catholic University, Danish Cancer Society Research Center, Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade do Porto, Universidad Nacional de Quilmes (UNQ), Faculty of Science, Aristotle University of Thessaloniki, Technical University of Denmark [Lyngby] (DTU), University of Cyprus (UCY), Charles University [Prague] (CU), Wellcome Trust Genome Campus, European Project: 778247,IDPfun, Department of Bio-engineering Sciences, Structural Biology Brussels, Università degli Studi di Padova = University of Padua (Unipd), Centre for Research and Technology Hellas (CERTH), Universidade do Porto = University of Porto, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), University of Cyprus [Nicosia] (UCY), Italian Ministry of University and Research (MIUR), PRIN 2017 under grant agreement no. 2017483NH8., and Ukupan broj autora: 61
Subjects: Process (engineering), AcademicSubjects/SCI00010, [SDV]Life Sciences [q-bio], Interoperability, Datasets as Topic, Biology, Ontology (information science), Intrinsically disordered proteins, World Wide Web, 03 medical and health sciences, Consistency (database systems), Annotation, 0302 clinical medicine, Genetics, Humans, Database Issue, Amino Acid Sequence, Databases, Protein, 030304 developmental biology, computer.programming_language, 0303 health sciences, Internet, Molecular Sequence Annotation, DNA, Intrinsically Disordered Proteins, Gene Ontology, 030220 oncology & carcinogenesis, RNA, Elixir (programming language), User interface, computer, Software, Protein Binding
Abstract: The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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34. A landscape of pharmacogenomic interactions in cancer

Author: Howard Lightfoot, Thomas Cokelaer, Xeni Mitropoulos, Patricia Greninger, Lodewyk F. A. Wessels, Ultan McDermott, Daniel A. Haber, Daniel J. Vis, Xianming Deng, Michael Schubert, Sergi Sayols, Jinhua Wang, Heshani de Silva, Maryam Soleimani, Manel Esteller, Nanne Aben, Laura Richardson, Nuria Lopez-Bigas, Cyril H. Benes, Ewald van Dyk, Julio Saez-Rodriguez, Sebastian Moran, Emanuel Gonçalves, Regina K. Egan, Tinghu Zhang, Graham R. Bignell, Michael R. Stratton, Syd Barthorpe, Nathanael S. Gray, Han Chang, Petra Ross-Macdonald, Tatiana Mironenko, Michael P. Menden, Theo A. Knijnenburg, Qingsong Liu, Holger Heyn, David Tamborero, Mathew J. Garnett, Francesco Iorio, Universitat de Barcelona, European Molecular Biology Laboratory, Wellcome Trust Genome Campus, European Bioinformatics Institute, The Wellcome Trust Sanger Institute [Cambridge], Institute for Systems Biology [Seattle] (ISB), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, RWTH Aachen University, Delft University of Technology (TU Delft), Massachusetts General Hospital [Charlestown, MA, États-Unis], Bristol-Myers Squibb Research and Development (BMS), Bellvitge Biomedical Research Institute, Partenaires INRAE, Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), IMIM-Hospital del Mar, Generalitat de Catalunya, Institució Catalana de Recerca i Estudis Avançats (ICREA), University of Barcelona, Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Cancer Genomics Netherlands [Rotterdam, The Netherlands], This work was funded by the Wellcome Trust (086375 and 102696). F.I. was supported by the European Bioinformatics Institute and Wellcome Trust Sanger Institute post-doctoral (ESPOD) program. T.A.K. was supported by the National Cancer Institute (U24CA143835) and the Netherlands Organization for Scientific Research. D.T. was supported by the People Programme (Marie Curie Actions) of the 7th Framework Programme of the European Union (FP7/2007-2013, 600388) and the Agency of Competitiveness for Companies of the Government of Catalonia (ACCIÓ). N.L.-B. was supported by La Fundació la Marató de TV3. M.E. was funded by the European Research Council (268626), the Ministerio de Ciencia e Innovacion (SAF2011-22803), the Institute of Health Carlos III (ISCIII) under the Integrated Project of Excellence (PIE13/00022), the Spanish Cancer Research Network (RD12/0036/0039), the Health and Science Departments of the Catalan Government Generalitat de Catalunya 2014-SGR 633, and the Cellex Foundation. U.M. was supported by a Cancer Research UK Clinician Scientist Fellowship. We thank Aiqing He for expression data and Ilya Shmulevich for assistance with the LOBICO framework. We thank P. Campbell, M. Ranzani, J. Brammeld, M. Petljak, F. Behan, C. Alsinet Armengol, H. Francies, V. Grinkevich, and A. 'Lilla' Mupo for useful comments. P.R.-M., H.C., and H.d.S. are employees and shareholders of Bristol-Myers Squibb. Research in the M.J.G. lab is supported in part with funding from AstraZeneca., European Project: 600388,EC:FP7:PEOPLE,FP7-PEOPLE-2012-COFUND,TECNIOSPRING(2013), European Project: 268626,EC:FP7:ERC,ERC-2010-AdG_20100317,EPINORC(2011), and Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH)
Subjects: 0301 basic medicine, MESH: Oncogenes, Carcinogenesis, [SDV]Life Sciences [q-bio], Gene Dosage, medicine.disease_cause, MESH: Gene Dosage, Medicaments antineoplàstics, MESH: DNA Methylation, Oncogènesi, Neoplasms, Antineoplastic agents, MESH: Neoplasms, MESH: Models, Genetic, Precision Medicine, Càncer, Càncer -- Aspectes genètics, Cancer, Genetics, Mutation, Phenotype, MESH: Drug Resistance, Neoplasm, 3. Good health, Fenotip, DNA methylation, Farmacogenètica, Càncer -- Tractament, Lineage (genetic), MESH: Mutation, MESH: Cell Line, Tumor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Biology, Gene dosage, MESH: Precision Medicine, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, MESH: Analysis of Variance, Cell Line, Tumor, medicine, Humans, Genomes, Resistència als medicaments, Analysis of Variance, MESH: Humans, Models, Genetic, Biochemistry, Genetics and Molecular Biology(all), Oncogenes, DNA Methylation, medicine.disease, Precision medicine, Genòmica, 030104 developmental biology, Drug Resistance, Neoplasm, Pharmacogenetics, Pharmacogenomics, Drug resistance, MESH: Antineoplastic Agents
Abstract: Cell 166(3), 740-754 (2016). doi:10.1016/j.cell.2016.06.017, Published by Elsevier, New York, NY

35. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression

Author: Cedric Notredame, Timo Lassmann, Carrie A. Davis, Thomas Derrien, Roderic Guigó, Tim Hubbard, Sarah Djebali, Julien Lagarde, Giovanni Bussotti, Gregory Guernec, Jennifer Harrow, José M. González, Yijun Ruan, Ramin Shiekhattar, Xiaoan Ruan, Angelika Merkel, Hagen Tilgner, David C. Martin, Mark G. Thomas, James B. Brown, Leonard Lipovich, Rory Johnson, Lavanya Veeravalli, Thomas R. Gingeras, Piero Carninci, Andrea Tanzer, David G. Knowles, Bioinformatics and Genomics, Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra [Barcelona], Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Fédératif de Recherche - Génétique Fonctionnelle Agronomie et Santé (IFR 140 GFAS), Plateforme bioinformatique GenOuest [Rennes], Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Plateforme Génomique Santé Biogenouest®-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec, Agency for Science, Technology and Research, Genome, Genome Institute of Singapore (GIS), Agency for Science, Technology and Research Genome, Riken Omics Science Center, Riken Yokohama Institute, Department of Statistics, University of California, Center for Molecular Medicine and Genetics, Wayne State University, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Cold Spring Harbor, Cold Spring Harbor Laboratory, The Wistar Institute, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra [Barcelona] (UPF), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Plateforme Génomique Santé Biogenouest®-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Wayne State University [Detroit], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Plateforme Génomique Santé Biogenouest®-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Université de Rennes (UR)-Plateforme Génomique Santé Biogenouest®-Inria Rennes – Bretagne Atlantique, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), and University of California (UC)
Subjects: Primates, Resource, Transcription, Genetic, Computational biology, Biology, Evolution, Molecular, Histones, Open Reading Frames, 03 medical and health sciences, 0302 clinical medicine, Databases, Genetic, Genetics, Animals, Cluster Analysis, Humans, RNA, Messenger, RNA Processing, Post-Transcriptional, Selection, Genetic, Gene, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genètica -- Bases de dades, Genetics (clinical), 030304 developmental biology, Cell Nucleus, Regulation of gene expression, 0303 health sciences, GENCODE, Gene Expression Profiling, Alternative splicing, Intron, Molecular Sequence Annotation, Exons, RNA no missatgers, Gene expression profiling, Alternative Splicing, Gene Expression Regulation, Organ Specificity, 030220 oncology & carcinogenesis, RNA splicing, RNA, Long Noncoding, Human genome, RNA Splice Sites
Abstract: The human genome contains many thousands of long noncoding RNAs (lncRNAs). While several studies have demonstrated compelling biological and disease roles for individual examples, analytical and experimental approaches to investigate these genes have been hampered by the lack of comprehensive lncRNA annotation. Here, we present and analyze the most complete human lncRNA annotation to date, produced by the GENCODE consortium within the framework of the ENCODE project and comprising 9277 manually annotated genes producing 14,880 transcripts. Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths. In contrast to protein-coding genes, however, lncRNAs display a striking bias toward two-exon transcripts, they are predominantly localized in the chromatin and nucleus, and a fraction appear to be preferentially processed into small RNAs. They are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes. Importantly, about one-third seem to have arisen within the primate lineage. Comprehensive analysis of their expression in multiple human organs and brain regions shows that lncRNAs are generally lower expressed than protein-coding genes, and display more tissue-specific expression patterns, with a large fraction of tissue-specific lncRNAs expressed in the brain. Expression correlation analysis indicates that lncRNAs show particularly striking positive correlation with the expression of antisense coding genes. This GENCODE annotation represents a valuable resource for future studies of lncRNAs. This work has been carried out under grants RD07/0067/0012, BIO2006-03380, and CSD2007-00050 from the Spanish Ministry of Science, grant SGR-1430 from the Catalan Government, grants 1U54HG004557-01 and 1U54HG004555-01 from the National Institutes of Health, and INBISCIII from Instituto de Salud Carlos III and FEDER. This research project has been cofinanced by the European Commission, within the 7th Framework Programme, Grant Agreement KBBE-2A-222664 (‘‘Quantomics’’). C.N. is financed by the Plan Nacional BFU2008-00419. G.B. is supported by the La Caixa Ph.D. program

36. The genome of the yellow potato cyst nematode, Globodera rostochiensis, reveals in-sights into the bases of parasitism and virulence

Author: Eves-Van Den Akker, S., Laetsch, D. R., Thorpe, P., Lilley, C. J., Danchin, E. G. J., Darocha, M., Rancurel, C., Holroyd, N. E., Cotton, J. A., Szitenberg, A., Grenier, E., Montarry, J., Mimee, B., Duceppe, M., Boyes, I., Marvin, J. M. C., Jones, L. M., Yusup, H. B., Lafond-Lapalme, J., Esquibet, M., Sabeh, M., Rott, M., Overmars, H., Finkers-Tomczak, A., Smant, G., Koutsovoulos, G., Blok, V., Mantelin, S., Cock, P. J. A., Phillips, W., Henrissat, B., Urwin, P. E., Mark Blaxter, Jones, J. T., Division of Plant Sciences, College of Life Sciences, University of Dundee, Institute of Evolutionary Biology, Cell and Molecular Sciences Group, Dundee Effector Consortium, The James Hutton Institute, Centre for Plant Sciences, University of Leeds, Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], School of Biological, Biomedical and Environmental Sciences, University of Hull, Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Horticulture Research and Development Centre, Agriculture and Agri-Food [Ottawa] (AAFC), Sidney Laboratory, Canadian Food Inspection Agency (CFIA), Laboratory of Nematology, Department of Plant Sciences, Wageningen University and Research Center (WUR), Information and Computational Sciences Group, Horticultural Crops Research Laboratory, USDA-ARS : Agricultural Research Service, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of Biological Sciences, The Open University [Milton Keynes] (OU), School of Biology, University of St Andrews, University of St Andrews [Scotland], Institut Sophia Agrobiotech (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Agriculture and Agri-Food (AAFC), Wageningen University and Research [Wageningen] (WUR), School of Biology [University of St Andrews], Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)
Subjects: Vertebrate Zoology, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Zoologie des vertébrés
Abstract: The yellow potato cyst nematode Globodera rostochiensis is a devastating plant pathogen of global economic importance, classified into pathotypes of different plant resistance-breaking phenotypes. G. rostochiensis secretes effectors, some of which were acquired by horizontal gene transfer (HGT), from pharyngeal glands into the host to manipulate host processes and promote parasitism. We generated a high-quality genome assembly for G. rostochiensis pathotype Ro1 and identified putative effectors and HGT events, mapped gene expression through the life cycle focusing on key parasitic transitions, and sequenced the genomes of eight populations including three additional pathotypes.

37. Pig genome sequence - analysis and publication strategy

Author: Alan L Archibald, Lars Bolund, Carol Churcher, Merete Fredholm, Martien A M Groenen, Barbara Harlizius, Kyung-Tai Lee, Denis Milan, Jane Rogers, Max F Rothschild, Hirohide Uenishi, Jun Wang, Lawrence B Schook, Swine Genome Sequencing Consortium, Archibald, Alan L., The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Beijing Genomics Institute [Shenzhen] (BGI), Institute of Human Genetics, Aarhus University [Aarhus], The Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], University of Copenhagen = Københavns Universitet (KU), Animal Breeding and Genomics Centre, Wageningen University and Research [Wageningen] (WUR), Institute for Pig Genetics, Partenaires INRAE, National Institute of Animal Science, 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, Genome Analysis Centre, Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University (ISU), National Institute of Agrobiological Sciences, Department of Biology, Northern Arizona University [Flagstaff], and Institute of Genomic Biology
Subjects: Cancer genome sequencing, lcsh:QH426-470, lcsh:Biotechnology, [SDV]Life Sciences [q-bio], Sus scrofa, genetic processes, information science, Sequence assembly, Genomics, Animal Breeding and Genomics, Biology, 03 medical and health sciences, lcsh:TP248.13-248.65, Correspondence, Genetics, Animals, Life Science, Fokkerij en Genomica, natural sciences, Exome sequencing, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, Genome, Shotgun sequencing, Publications, 0402 animal and dairy science, food and beverages, Sequence Analysis, DNA, 04 agricultural and veterinary sciences, Genome project, 040201 dairy & animal science, lcsh:Genetics, WIAS, Reference genome, Biotechnology
Abstract: Background The pig genome is being sequenced and characterised under the auspices of the Swine Genome Sequencing Consortium. The sequencing strategy followed a hybrid approach combining hierarchical shotgun sequencing of BAC clones and whole genome shotgun sequencing. Results Assemblies of the BAC clone derived genome sequence have been annotated using the Pre-Ensembl and Ensembl automated pipelines and made accessible through the Pre-Ensembl/Ensembl browsers. The current annotated genome assembly (Sscrofa9) was released with Ensembl 56 in September 2009. A revised assembly (Sscrofa10) is under construction and will incorporate whole genome shotgun sequence (WGS) data providing > 30× genome coverage. The WGS sequence, most of which comprise short Illumina/Solexa reads, were generated from DNA from the same single Duroc sow as the source of the BAC library from which clones were preferentially selected for sequencing. In accordance with the Bermuda and Fort Lauderdale agreements and the more recent Toronto Statement the data have been released into public sequence repositories (Genbank/EMBL, NCBI/Ensembl trace repositories) in a timely manner and in advance of publication. Conclusions In this marker paper, the Swine Genome Sequencing Consortium (SGSC) sets outs its plans for analysis of the pig genome sequence, for the application and publication of the results.
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38. Phenotypic variation in the lipopolysaccharide O-antigen of Salmonella Paratyphi A and implications for vaccine development.

Author: Mylona E, Pereira-Dias J, Keane JA, Karkey A, Dongol S, Khokhar F, Tran TA, Cormie C, Higginson E, and Baker S
Abstract: Enteric fever remains a major public health problem in South and Southeast Asia. The recent roll-out of the typhoid conjugate vaccine protecting against S. Typhi exhibits great promise for disease reduction in high burden areas. However, some endemic regions remain vulnerable to S. Paratyphi A due to a lack of licensed vaccines and inadequate WASH. Several developmental S. Paratyphi A vaccines exploit O-antigen as the target antigen. It has been hypothesised that O-antigen is under selective and environmental pressure, with mutations in O-antigen biosynthesis genes being reported, but their phenotypic effects are unknown. Here, we aimed to evaluate O-antigen variation in S. Paratyphi A originating from Nepal, and the potential effect of this variation on antibody binding. O-antigen variation was determined by measuring LPS laddering shift following electrophoresis; this analysis was complemented with genomic characterisation of the O-antigen region. We found structural O-antigen variation in <10 % of S. Paratyphi A organisms, but a direct underlying genetic cause could not be identified. High-content imaging was performed to determine antibody binding by commercial O2 monoclonal (mAb) and polyclonal antibodies, as well as polyclonal sera from convalescent patients naturally infected with S. Paratyphi A. Commercial mAbs detected only a fraction of an apparently "clonal" bacterial population, suggesting phase variation and nonuniform O-antigen composition. Notably, and despite visible subpopulation clusters, O-antigen structural changes did not appear to affect the binding ability of polyclonal human antibody considerably, which led to no obvious differences in the functionality of antibodies targeting organisms with different O-antigen conformations. Although these results need to be confirmed in organisms from alternative endemic areas, they are encouraging the use of O-antigen as the target antigen in S. Paratyphi A vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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39. Single-cell RNA sequencing offers opportunities to explore the depth of physiology, adaptation, and biochemistry in non-model organisms exposed to pollution.

Author: Collí-Dulá RC and Papatheodorou I
Abstract: Single-cell Sequencing technology (scSeq) has revolutionized our understanding of individual cells, uncovering unprecedented heterogeneity within tissues and cell populations, principality through single-cell RNA Sequencing (scRNA-Seq). This short review highlights the pivotal role of scRNA-Seq in elucidating genotype-phenotype relationships, particularly in biological systems. Based on published articles, our analysis involved manual curation and automated Scopus tools to illustrate recent advances in the application of scRNA-Seq. The results reveal that scRNA-Seq has been extensively utilized in various biological areas, including biochemistry, genetics, molecular biology, immunology, and microbiology, followed by health sciences covering studies related to the nervous system, immune system, human health, development, and diseases, with a particular focus on cancer research. However, the potential of scRNA-Seq extends beyond disease research, offering insights into non-model organisms' responses to environmental contaminants. By enabling the study of cellular reactions at a molecular level, scRNA-Seq provides a comprehensive understanding of intracellular heterogeneity that enhances our comprehension of physiological, biochemical, and pathological environmental impacts on non-model organisms exposed to pollution. This understanding has many practical benefits, as it can aid in regulation and conservation efforts that benefit the environment and the use of economically essential and ecologically relevant organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2024
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40. High-resolution functional mapping of RAD51C by saturation genome editing.

Author: Olvera-León R, Zhang F, Offord V, Zhao Y, Tan HK, Gupta P, Pal T, Robles-Espinoza CD, Arriaga-González FG, Matsuyama LSAS, Delage E, Dicks E, Ezquina S, Rowlands CF, Turnbull C, Pharoah P, Perry JRB, Jasin M, Waters AJ, and Adams DJ
Subjects: Humans, Female, Breast Neoplasms genetics, Alleles, CRISPR-Cas Systems genetics, Gene Editing methods, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, Ovarian Neoplasms genetics
Abstract: Pathogenic variants in RAD51C confer an elevated risk of breast and ovarian cancer, while individuals homozygous for specific RAD51C alleles may develop Fanconi anemia. Using saturation genome editing (SGE), we functionally assess 9,188 unique variants, including >99.5% of all possible coding sequence single-nucleotide alterations. By computing changes in variant abundance and Gaussian mixture modeling (GMM), we functionally classify 3,094 variants to be disruptive and use clinical truth sets to reveal an accuracy/concordance of variant classification >99.9%. Cell fitness was the primary assay readout allowing us to observe a phenomenon where specific missense variants exhibit distinct depletion kinetics potentially suggesting that they represent hypomorphic alleles. We further explored our exhaustive functional map, revealing critical residues on the RAD51C structure and resolving variants found in cancer-segregating kindred. Furthermore, through interrogation of UK Biobank and a large multi-center ovarian cancer cohort, we find significant associations between SGE-depleted variants and cancer diagnoses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
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41. Polyclonality overcomes fitness barriers in Apc-driven tumorigenesis.

Author: Sadien ID, Adler S, Mehmed S, Bailey S, Sawle A, Couturier DL, Eldridge M, Adams DJ, Kemp R, Lourenço FC, and Winton DJ
Subjects: Animals, Mice, Female, Male, Proto-Oncogene Proteins c-myc metabolism, Proto-Oncogene Proteins c-myc genetics, Intestinal Neoplasms genetics, Intestinal Neoplasms pathology, Intestinal Neoplasms metabolism, Cell Lineage, Genetic Fitness, Clone Cells metabolism, Signal Transduction, Genes, APC, Humans, Cell Transformation, Neoplastic genetics, Carcinogenesis genetics, Carcinogenesis pathology, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Adenomatous Polyposis Coli Protein genetics, Adenomatous Polyposis Coli Protein metabolism, Neoplastic Stem Cells pathology, Neoplastic Stem Cells metabolism, Mutation
Abstract: Loss-of-function mutations in the tumour suppressor APC are an initial step in intestinal tumorigenesis 1,2 . APC-mutant intestinal stem cells outcompete their wild-type neighbours through the secretion of Wnt antagonists, which accelerates the fixation and subsequent rapid clonal expansion of mutants 3-5 . Reports of polyclonal intestinal tumours in human patients and mouse models appear at odds with this process 6,7 . Here we combine multicolour lineage tracing with chemical mutagenesis in mice to show that a large proportion of intestinal tumours have a multiancestral origin. Polyclonal tumours retain a structure comprising subclones with distinct Apc mutations and transcriptional states, driven predominantly by differences in KRAS and MYC signalling. These pathway-level changes are accompanied by profound differences in cancer stem cell phenotypes. Of note, these findings are confirmed by introducing an oncogenic Kras mutation that results in predominantly monoclonal tumour formation. Further, polyclonal tumours have accelerated growth dynamics, suggesting a link between polyclonality and tumour progression. Together, these findings demonstrate the role of interclonal interactions in promoting tumorigenesis through non-cell autonomous pathways that are dependent on the differential activation of oncogenic pathways between clones., (© 2024. The Author(s).)
Published: 2024
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42. IntAct Database for Accessing IMEx's Contextual Metadata of Molecular Interactions.

Author: Panneerselvam K, Porras P, Del-Toro N, Perfetto L, Shrivastava A, Ragueneau E, Reyes JJM, Orchard S, and Hermjakob H
Subjects: Humans, Databases, Protein, Databases, Factual, Computational Biology methods, User-Computer Interface, Protein Interaction Mapping methods, Metadata
Abstract: The International Molecular Exchange Consortium (IMEx) has evolved into a vital partnership of open resources dedicated to curating molecular interaction data from the scientific literature. This consortium, which includes IntAct, MINT, MatrixDB, and DIP, is a collaborative effort with a central mission of aggregating detailed molecular interaction experimental evidence in a machine-readable format, supported by controlled vocabularies and standard ontologies. The IntAct molecular interaction database (www.ebi.ac.uk/intact), as an IMEx partner, serves as a valuable portal for accessing IMEx data through user-friendly search options and an array of interactive filters. The resource currently hosts an extensive repository of 1,293,508 binary interactions meticulously captured from 75,098 experiments documented in 23,366 publications (as of the February 2024 release), with this corpora being added to by regular data releases. IMEx curation policy has consistently prioritized a fine-grained data and curation model, with a focus on capturing the relevant experimental details essential for interpreting molecular interaction data effectively. Our curation process is designed to support the generation of interactomes tailored to contexts such as disease-specific or tissue-/cell-type-specific interactomes. These interactions are ranked according to a scoring system based on the Proteomics Standard Initiative Molecular Interaction (PSI MI) standards. This scoring system allows users to assess the degree of confidence in binary interactions, enhancing the value of the data. The resource provides insights into the nature of relationships among interacting partners as defined by the experimental setup and the associated biological context. Interactive filters enable users to navigate these rich, multilayered data, promoting a deeper understanding of biological complexity. Additionally, the IntAct website fosters the creation of networks for collaborative analyses by the scientific community. The recent transformation of the IntAct website, supported by a graph-type database, empowers users to execute custom queries tailored to their specific research interests. This article illustrates the diverse levels of annotations available for interactions and the multiple search options at users' disposal to access data of interest. © 2024 European Molecular Biology Laboratory, European Bioinformatics Institute. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Using Quick Search, network visualization, and filters Support Protocol: Accessing fine annotations from intact: Unlocking the molecular details Alternate Protocol: Using batch search: Querying multiple interactors Basic Protocol 2: Using advanced search: Precision and customization., (© 2024 European Molecular Biology Laboratory, European Bioinformatics Institute. Current Protocols published by Wiley Periodicals LLC.)
Published: 2024
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43. Integration of variant annotations using deep set networks boosts rare variant association testing.

Author: Clarke B, Holtkamp E, Öztürk H, Mück M, Wahlberg M, Meyer K, Munzlinger F, Brechtmann F, Hölzlwimmer FR, Lindner J, Chen Z, Gagneur J, and Stegle O
Subjects: Humans, Neural Networks, Computer, Phenotype, Exome Sequencing methods, Genome-Wide Association Study methods, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Biological Specimen Banks, Genetic Association Studies methods, Genetic Predisposition to Disease, Genetic Variation
Abstract: Rare genetic variants can have strong effects on phenotypes, yet accounting for rare variants in genetic analyses is statistically challenging due to the limited number of allele carriers and the burden of multiple testing. While rich variant annotations promise to enable well-powered rare variant association tests, methods integrating variant annotations in a data-driven manner are lacking. Here we propose deep rare variant association testing (DeepRVAT), a model based on set neural networks that learns a trait-agnostic gene impairment score from rare variant annotations and phenotypes, enabling both gene discovery and trait prediction. On 34 quantitative and 63 binary traits, using whole-exome-sequencing data from UK Biobank, we find that DeepRVAT yields substantial gains in gene discoveries and improved detection of individuals at high genetic risk. Finally, we demonstrate how DeepRVAT enables calibrated and computationally efficient rare variant tests at biobank scale, aiding the discovery of genetic risk factors for human disease traits., (© 2024. The Author(s).)
Published: 2024
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44. A research data management (RDM) community for ELIXIR.

Author: D'Anna F, Jareborg N, Jetten M, Ahokas M, Alper P, Andrews R, Bösl K, D'Altri T, Faria D, Fatima N, Fuchs S, Garrard C, Gu W, Heil KF, Kallberg Y, Licciulli F, Lübke NC, Melo AMP, Mičetić I, Oliveira J, Oulas A, Palagi PM, Poterlowicz K, Perez-Sitja X, Ruch P, Sansone SA, Schnitzer H, van Gelder C, Vergoulis T, Wibberg D, Wittig U, Leskošek B, Vondrasek J, and Andrabi M
Subjects: Humans, Research, Data Management methods
Abstract: Research data management (RDM) is central to the implementation of the FAIR (Findable Accessible, Interoperable, Reusable) and Open Science principles. Recognising the importance of RDM, ELIXIR Platforms and Nodes have invested in RDM and launched various projects and initiatives to ensure good data management practices for scientific excellence. These projects have resulted in a rich set of tools and resources highly valuable for FAIR data management. However, these resources remain scattered across projects and ELIXIR structures, making their dissemination and application challenging. Therefore, it becomes imminent to coordinate these efforts for sustainable and harmonised RDM practices with dedicated forums for RDM professionals to exchange knowledge and share resources. The proposed ELIXIR RDM Community will bring together RDM experts to develop ELIXIR's vision and coordinate its activities, taking advantage of the available assets. It aims to coordinate RDM best practices and illustrate how to use the existing ELIXIR RDM services. The Community will be built around three integral pillars, namely, a network of RDM professionals, RDM knowledge management and RDM training expertise and resources. It will also engage with external stakeholders to leverage benefits and provide a forum to RDM professionals for regular knowledge exchange, capacity building and development of harmonised RDM practices, keeping in line with the overall scope of the RDM Community. In the short term, the Community aims to build upon the existing resources and ensure that the content of these remain up to date and fit for purpose. In the long run, the Community will aim to strengthen the skills and knowledge of its RDM professionals to support the emerging needs of the scientific community. The Community will also devise an effective strategy to engage with other ELIXIR structures and international stakeholders to influence and align with developments and solutions in the RDM field., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 D'Anna F et al.)
Published: 2024
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45. Phenotypic spectrum of dual diagnoses in developmental disorders.

Author: Ridsdale AM, Dickerson A, Chundru VK, Firth HV, and Wright CF
Abstract: As more patients receive genome-wide sequencing, the number of individuals diagnosed with multiple monogenic conditions is increasing. We sought to investigate the relative phenotypic contribution of dual diagnoses using both manual curation and computational approaches. First, we computed 1,003,236 semantic similarity scores for all possible pairs of 1,417 genes in the Developmental Disorder Gene2Phenotype (DDG2P) database using Human Phenotype Ontology terms. Next, for 62 probands with two molecular diagnoses in the Deciphering Developmental Disorders study, we computed semantic similarity scores between the probands' phenotypes and DDG2P phenotypes associated with the two disorders and compared the results with manual attribution of proband phenotypes to none, one, or both of the genes. We found a spectrum of phenotypic similarity for dual diagnoses, both across all DDG2P genes and within dual diagnosed probands, from phenotypically distinct through blended to indistinguishable conditions. Pairwise semantic similarity scores between two DDG2P genes were a good predictor of the extent of phenotypic blending observed in probands. Dual diagnoses involving genes linked with synergistic phenotypes can result in more extreme presentations while those involving antagonistic phenotypes have spuriously high pairwise semantic similarity scores despite a potentially milder atypical presentation. We suggest that the phenotypic contribution of two molecular diagnoses may contain discrete, synergistic, or antagonistic elements. Conceptual recognition of this phenotypic spectrum is important for making a final clinico-molecular diagnosis and providing accurate genetic counseling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
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46. A New Method for Conditional Gene-Based Analysis Effectively Accounts for the Regional Polygenic Background.

Author: Svishcheva GR, Belonogova NM, Kirichenko AV, Tsepilov YA, and Axenovich TI
Subjects: Humans, Genome-Wide Association Study methods, Models, Genetic, Genotype, Polymorphism, Single Nucleotide genetics, Multifactorial Inheritance genetics, Linkage Disequilibrium
Abstract: Gene-based association analysis is a powerful tool for identifying genes that explain trait variability. An essential step of this analysis is a conditional analysis. It aims to eliminate the influence of SNPs outside the gene, which are in linkage disequilibrium with intragenic SNPs. The popular conditional analysis method, GCTA-COJO, accounts for the influence of several top independently associated SNPs outside the gene, correcting the z statistics for intragenic SNPs. We suggest a new TauCOR method for conditional gene-based analysis using summary statistics. This method accounts the influence of the full regional polygenic background, correcting the genotype correlations between intragenic SNPs. As a result, the distribution of z statistics for intragenic SNPs becomes conditionally independent of distribution for extragenic SNPs. TauCOR is compatible with any gene-based association test. TauCOR was tested on summary statistics simulated under different scenarios and on real summary statistics for a 'gold standard' gene list from the Open Targets Genetics project. TauCOR proved to be effective in all modelling scenarios and on real data. The TauCOR's strategy showed comparable sensitivity and higher specificity and accuracy than GCTA-COJO on both simulated and real data. The method can be successfully used to improve the effectiveness of gene-based association analyses.
Published: 2024
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47. The lipidomics reporting checklist a framework for transparency of lipidomic experiments and repurposing resource data.

Author: Kopczynski D, Ejsing CS, McDonald JG, Bamba T, Baker ES, Bertrand-Michel J, Brügger B, Coman C, Ellis SR, Garrett TJ, Griffiths WJ, Guan XL, Han X, Höring M, Holčapek M, Hoffmann N, Huynh K, Lehmann R, Jones JW, Kaddurah-Daouk R, Köfeler HC, Meikle PJ, Metz TO, O'Donnell VB, Saigusa D, Schwudke D, Shevchenko A, Torta F, Vizcaíno JA, Welti R, Wenk MR, Wolrab D, Xia Y, Ekroos K, Ahrends R, and Liebisch G
Subjects: Humans, Lipids analysis, Lipids chemistry, Lipidomics methods, Lipidomics standards, Checklist
Abstract: The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research., Competing Interests: Conflict of interests Kaddurah-Daouk is an inventor on key patents in the field of metabolomics and hold equity in Metabolon, a biotech company in North Carolina. In addition, she holds patents licensed to Chymia LLC and PsyProtix with royalties and ownership. Kim Ekroos is the owner of Lipidomics Consulting Ltd., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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48. Leave no transcripts behind.

Author: Moy M, Kyany'a C, and Maes M
Published: 2024
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49. RBPs: an RNA editor's choice.

Author: Fierro-Monti I
Abstract: RNA-binding proteins (RBPs) play a key role in gene expression and post-transcriptional RNA regulation. As integral components of ribonucleoprotein complexes, RBPs are susceptible to genomic and RNA Editing derived amino acid substitutions, impacting functional interactions. This article explores the prevalent RNA Editing of RBPs, unravelling the complex interplay between RBPs and RNA Editing events. Emphasis is placed on their influence on single amino acid variants (SAAVs) and implications for disease development. The role of Proteogenomics in identifying SAAVs is briefly discussed, offering insights into the RBP landscape. RNA Editing within RBPs emerges as a promising target for precision medicine, reshaping our understanding of genetic and epigenetic variations in health and disease., 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 Fierro-Monti.)
Published: 2024
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50. Natural products from food sources can alter the spread of antimicrobial resistance plasmids in Enterobacterales .

Author: Alav I, Pordelkhaki P, Rodriguez-Navarro J, Neo O, Kessler C, Awodipe RJ, Cliffe P, Pulavan N, Marton HL, Gibbons S, and Buckner MMC
Subjects: Drug Resistance, Bacterial genetics, Conjugation, Genetic, Bacterial Proteins genetics, Bacterial Proteins metabolism, Enterobacteriaceae drug effects, Enterobacteriaceae genetics, Microbial Sensitivity Tests, Food Microbiology, Gene Transfer, Horizontal, Plasmids genetics, Anti-Bacterial Agents pharmacology, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae genetics, Escherichia coli genetics, Escherichia coli drug effects, beta-Lactamases genetics, beta-Lactamases metabolism, Biological Products pharmacology
Abstract: Antimicrobial resistance (AMR) poses a significant threat to global public health. Notably, resistance to carbapenem and extended-spectrum β-lactam antibiotics in Gram-negative bacteria is a major impediment to treating infections. Genes responsible for antibiotic resistance are frequently carried on plasmids, which can transfer between bacteria. Therefore, exploring strategies to prevent this transfer and the prevalence of AMR plasmids is timely and pertinent. Here, we show that certain natural product extracts and associated pure compounds can reduce the conjugation of AMR plasmids into new bacterial hosts. Using our established high-throughput fluorescence-based flow cytometry assay, we found that the natural products were more active in reducing transmission of the IncK extended-spectrum β-lactamase-encoding plasmid pCT in Escherichia coli EC958c, compared to Klebsiella pneumoniae Ecl8 carrying the IncFII carbapenemase-encoding plasmid pKpQIL. The exception was the natural product rottlerin, also active in K. pneumoniae . In classical conjugation assays, rottlerin also reduced the conjugation frequency of the IncFII bla NDM-1 carrying plasmid pCPE16_3 from a clinical K. pneumoniae isolate. Our data indicate that the natural products tested here, in their current molecular structure, reduced conjugation by a small amount, which is unlikely to achieve a large-scale reduction in AMR in bacterial populations. However, certain natural products like rottlerin could provide a foundation for further research into compounds with effective anti-plasmid activity.
Published: 2024
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