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  • 11
    Publication Date: 2002-03-16
    Description: An outbreak of paralytic poliomyelitis occurred in the Dominican Republic (13 confirmed cases) and Haiti (8 confirmed cases, including 2 fatal cases) during 2000-2001. All but one of the patients were either unvaccinated or incompletely vaccinated children, and cases occurred in communities with very low (7 to 40%) rates of coverage with oral poliovirus vaccine (OPV). The outbreak was associated with the circulation of a derivative of the type 1 OPV strain, probably originating from a single OPV dose given in 1998-1999. The vaccine-derived poliovirus associated with the outbreak had biological properties indistinguishable from those of wild poliovirus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kew, Olen -- Morris-Glasgow, Victoria -- Landaverde, Mauricio -- Burns, Cara -- Shaw, Jing -- Garib, Zacarias -- Andre, Jean -- Blackman, Elizabeth -- Freeman, C Jason -- Jorba, Jaume -- Sutter, Roland -- Tambini, Gina -- Venczel, Linda -- Pedreira, Cristina -- Laender, Fernando -- Shimizu, Hiroyuki -- Yoneyama, Tetsuo -- Miyamura, Tatsuo -- van Der Avoort, Harrie -- Oberste, M Steven -- Kilpatrick, David -- Cochi, Stephen -- Pallansch, Mark -- de Quadros, Ciro -- New York, N.Y. -- Science. 2002 Apr 12;296(5566):356-9. Epub 2002 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA 30333, USA. okew@cdc.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11896235" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions ; Adolescent ; Animals ; Capsid/genetics ; Capsid Proteins ; Child ; Child, Preschool ; *Disease Outbreaks ; Dominican Republic/epidemiology ; Female ; Genes, Viral ; Haiti/epidemiology ; Humans ; Immunization Programs ; Infant ; Male ; Mice ; Molecular Sequence Data ; Point Mutation ; Poliomyelitis/*epidemiology/prevention & control/transmission/*virology ; Poliovirus/classification/*genetics/isolation & purification/*pathogenicity ; Poliovirus Vaccine, Oral/*adverse effects ; Population Surveillance ; Recombination, Genetic ; Vaccination ; Virulence
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 12
    Publication Date: 2003-05-06
    Description: We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marra, Marco A -- Jones, Steven J M -- Astell, Caroline R -- Holt, Robert A -- Brooks-Wilson, Angela -- Butterfield, Yaron S N -- Khattra, Jaswinder -- Asano, Jennifer K -- Barber, Sarah A -- Chan, Susanna Y -- Cloutier, Alison -- Coughlin, Shaun M -- Freeman, Doug -- Girn, Noreen -- Griffith, Obi L -- Leach, Stephen R -- Mayo, Michael -- McDonald, Helen -- Montgomery, Stephen B -- Pandoh, Pawan K -- Petrescu, Anca S -- Robertson, A Gordon -- Schein, Jacqueline E -- Siddiqui, Asim -- Smailus, Duane E -- Stott, Jeff M -- Yang, George S -- Plummer, Francis -- Andonov, Anton -- Artsob, Harvey -- Bastien, Nathalie -- Bernard, Kathy -- Booth, Timothy F -- Bowness, Donnie -- Czub, Martin -- Drebot, Michael -- Fernando, Lisa -- Flick, Ramon -- Garbutt, Michael -- Gray, Michael -- Grolla, Allen -- Jones, Steven -- Feldmann, Heinz -- Meyers, Adrienne -- Kabani, Amin -- Li, Yan -- Normand, Susan -- Stroher, Ute -- Tipples, Graham A -- Tyler, Shaun -- Vogrig, Robert -- Ward, Diane -- Watson, Brynn -- Brunham, Robert C -- Krajden, Mel -- Petric, Martin -- Skowronski, Danuta M -- Upton, Chris -- Roper, Rachel L -- New York, N.Y. -- Science. 2003 May 30;300(5624):1399-404. Epub 2003 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉British Columbia Cancer Agency (BCCA) Genome Sciences Centre, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. mmarra@bccgsc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730501" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Animals ; Base Sequence ; Conserved Sequence ; Coronavirus/classification/genetics ; DNA, Complementary ; Frameshifting, Ribosomal ; *Genome, Viral ; Humans ; Membrane Glycoproteins/chemistry/genetics ; Nucleocapsid Proteins/chemistry/genetics ; Open Reading Frames ; Phylogeny ; RNA Replicase/chemistry/genetics ; RNA, Viral/*genetics/isolation & purification ; Regulatory Sequences, Nucleic Acid ; SARS Virus/classification/*genetics/isolation & purification ; Sequence Analysis, DNA ; Severe Acute Respiratory Syndrome/virology ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins/chemistry/genetics ; Viral Matrix Proteins/chemistry/genetics ; Viral Proteins/chemistry/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 13
    Publication Date: 2005-10-15
    Description: Genetic maps, which document the way in which recombination rates vary over a genome, are an essential tool for many genetic analyses. We present a high-resolution genetic map of the human genome, based on statistical analyses of genetic variation data, and identify more than 25,000 recombination hotspots, together with motifs and sequence contexts that play a role in hotspot activity. Differences between the behavior of recombination rates over large (megabase) and small (kilobase) scales lead us to suggest a two-stage model for recombination in which hotspots are stochastic features, within a framework in which large-scale rates are constrained.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myers, Simon -- Bottolo, Leonardo -- Freeman, Colin -- McVean, Gil -- Donnelly, Peter -- U54 HG2750/HG/NHGRI NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2005 Oct 14;310(5746):321-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16224025" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Chromosome Mapping ; Chromosomes, Human ; Evolution, Molecular ; Female ; *Genome, Human ; Humans ; Male ; Models, Genetic ; Polymorphism, Single Nucleotide ; Recombination, Genetic/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 14
    Publication Date: 1993-11-05
    Description: Although presentation of antigen to the T cell receptor is necessary for the initiation of an immune response, additional molecules expressed on antigen-presenting cells deliver essential costimulatory signals. T cell activation, in the absence of costimulation, results in T cell anergy. The B7-1 protein is a costimulator molecule that regulates interleukin-2 (IL-2) secretion by signaling through the pathway that uses CD28 and CTLA-4 (hereafter referred to as the CD28 pathway). We have cloned a counter-receptor of CD28 and CTLA-4, termed B7-2. Although only 26 percent identical to B7-1, B7-2 also costimulates IL-2 production and T cell proliferation. Unlike B7-1, B7-2 messenger RNA is constitutively expressed in unstimulated B cells. It is likely that B7-2 provides a critical early costimulatory signal determining if the T cell will contribute to an immune response or become anergic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freeman, G J -- Gribben, J G -- Boussiotis, V A -- Ng, J W -- Restivo, V A Jr -- Lombard, L A -- Gray, G S -- Nadler, L M -- CA 40216/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 5;262(5135):909-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematologic Malignancies, Dana-Farber Cancer Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7694363" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Amino Acid Sequence ; Animals ; *Antigens, CD ; Antigens, CD28/metabolism ; Antigens, CD80/chemistry/genetics/*immunology/metabolism ; Antigens, CD86 ; Antigens, Differentiation/*metabolism ; B-Lymphocytes/*immunology/metabolism ; CTLA-4 Antigen ; Cell Line ; *Cloning, Molecular ; DNA, Complementary/genetics ; Humans ; *Immunoconjugates ; *Lymphocyte Activation ; *Membrane Glycoproteins ; Molecular Sequence Data ; Sequence Alignment ; Signal Transduction ; T-Lymphocytes/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 2002-06-22
    Description: Many biological processes are initiated by cooperative assembly of large multicomponent complexes; however, mechanisms for modulating or terminating the actions of these complexes are not well understood. For example, hormone-bound intracellular receptors (IRs) nucleate formation of transcriptional regulatory complexes whose actions cease promptly upon hormone withdrawal. Here, we show that the p23 molecular chaperone localizes in vivo to genomic response elements in a hormone-dependent manner, disrupting receptor-mediated transcriptional activation in vivo and in vitro; Hsp90 weakly displayed similar activities. Indeed, p23 and Hsp90 also disrupted the activities of some non-IR-containing transcriptional regulatory complexes. We suggest that molecular chaperones promote disassembly of transcriptional regulatory complexes, thus enabling regulatory machineries to detect and respond to signaling changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freeman, Brian C -- Yamamoto, Keith R -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2232-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12077419" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA/metabolism ; Dexamethasone/metabolism/pharmacology ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/*metabolism ; HeLa Cells ; Humans ; Molecular Chaperones/*metabolism ; Nuclear Receptor Coactivator 2 ; Phosphoproteins/*metabolism ; Promoter Regions, Genetic ; Rats ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Receptors, Glucocorticoid/metabolism ; Receptors, Retinoic Acid/metabolism ; Receptors, Thyroid Hormone/metabolism ; Recombinant Fusion Proteins/metabolism ; *Response Elements ; Retinoid X Receptors ; Transcription Factors/metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Tryptophan Oxygenase/genetics ; Tumor Cells, Cultured ; Tyrosine Transaminase/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 16
    Publication Date: 2011-11-01
    Description: Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224101/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224101/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baillie, J Kenneth -- Barnett, Mark W -- Upton, Kyle R -- Gerhardt, Daniel J -- Richmond, Todd A -- De Sapio, Fioravante -- Brennan, Paul M -- Rizzu, Patrizia -- Smith, Sarah -- Fell, Mark -- Talbot, Richard T -- Gustincich, Stefano -- Freeman, Thomas C -- Mattick, John S -- Hume, David A -- Heutink, Peter -- Carninci, Piero -- Jeddeloh, Jeffrey A -- Faulkner, Geoffrey J -- 090385/Wellcome Trust/United Kingdom -- 090385/Z/09/Z/Wellcome Trust/United Kingdom -- BB/H005935/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2011 Oct 30;479(7374):534-7. doi: 10.1038/nature10531.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22037309" target="_blank"〉PubMed〈/a〉
    Keywords: Alu Elements/genetics ; Base Sequence/genetics ; Brain/*metabolism ; Caudate Nucleus/metabolism ; Clonal Evolution/genetics ; DNA Copy Number Variations/genetics ; Epistasis, Genetic ; Genome, Human/genetics ; Germ-Line Mutation/*genetics ; Hippocampus/metabolism ; Histone Deacetylase 1/genetics ; Humans ; Mosaicism ; Mutagenesis, Insertional/*genetics ; Nerve Tissue Proteins/genetics ; Organ Specificity/genetics ; Polymerase Chain Reaction ; Retroelements/*genetics ; Transcription Factors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 17
    Publication Date: 2014-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freeman, Richard B -- Huang, Wei -- England -- Nature. 2014 Sep 18;513(7518):305. doi: 10.1038/513305a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Bureau of Economic Research, and professor of economics at Harvard University in Cambridge, Massachusetts, USA. ; Harvard University.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25230634" target="_blank"〉PubMed〈/a〉
    Keywords: *Authorship ; *Bibliometrics ; Communication Barriers ; *Cooperative Behavior ; Creativity ; *Cultural Diversity ; Ethnic Groups/ethnology/*statistics & numerical data ; Humans ; International Cooperation ; Journal Impact Factor ; *Names ; Research Personnel/*statistics & numerical data/supply & distribution
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 18
    Publication Date: 2015-03-20
    Description: Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide single nucleotide polymorphism (SNP) data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom. This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography. The regional genetic differentiation and differing patterns of shared ancestry with 6,209 individuals from across Europe carry clear signals of historical demographic events. We estimate the genetic contribution to southeastern England from Anglo-Saxon migrations to be under half, and identify the regions not carrying genetic material from these migrations. We suggest significant pre-Roman but post-Mesolithic movement into southeastern England from continental Europe, and show that in non-Saxon parts of the United Kingdom, there exist genetically differentiated subgroups rather than a general 'Celtic' population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632200/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632200/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Stephen -- Winney, Bruce -- Hellenthal, Garrett -- Davison, Dan -- Boumertit, Abdelhamid -- Day, Tammy -- Hutnik, Katarzyna -- Royrvik, Ellen C -- Cunliffe, Barry -- Wellcome Trust Case Control Consortium 2 -- International Multiple Sclerosis Genetics Consortium -- Lawson, Daniel J -- Falush, Daniel -- Freeman, Colin -- Pirinen, Matti -- Myers, Simon -- Robinson, Mark -- Donnelly, Peter -- Bodmer, Walter -- 072974/Wellcome Trust/United Kingdom -- 072974/Z/03/Z/Wellcome Trust/United Kingdom -- 075491/Wellcome Trust/United Kingdom -- 075491/Z/04/A/Wellcome Trust/United Kingdom -- 075491/Z/04/B/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084818/Wellcome Trust/United Kingdom -- 084818/Z/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 085475DONNELLY/Wellcome Trust/United Kingdom -- 088262/Wellcome Trust/United Kingdom -- 088262/Z/09/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 095552/Z/11/Z/Wellcome Trust/United Kingdom -- 098386/Wellcome Trust/United Kingdom -- 098386/Z/12/Z/Wellcome Trust/United Kingdom -- 098387/Wellcome Trust/United Kingdom -- 098387/Z/12/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Mar 19;519(7543):309-14. doi: 10.1038/nature14230.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia [2] University of Melbourne, Department of Mathematics and Statistics, Parkville, Victoria 3010, Australia [3] University of Oxford, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. ; University of Oxford, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. ; University College London Genetics Institute, Darwin Building, Gower Street, London WC1E 6BT, UK. ; Counsyl, 180 Kimball Way, South San Francisco, California 94080, USA. ; University of Oxford, Institute of Archaeology, 36 Beaumont Street, Oxford OX1 2PG, UK. ; University of Bristol, Department of Mathematics, University Walk, Bristol BS8 1TW, UK. ; College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK. ; The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK. ; University of Helsinki, P.O. Box 20, Helsinki, FI-00014, Finland. ; University of Oxford, Department of Statistics, 1 South Parks Road, Oxford OX1 3TG, UK. ; University of Oxford, University Museum of Natural History, Parks Road, Oxford OX1 3PW, UK. ; 1] The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK [2] University of Oxford, Department of Statistics, 1 South Parks Road, Oxford OX1 3TG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25788095" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; European Continental Ancestry Group/genetics ; *Genetics, Population ; Great Britain/ethnology ; Haplotypes/*genetics ; Humans ; Polymorphism, Single Nucleotide/*genetics ; Principal Component Analysis
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  • 19
    Publication Date: 2011-08-13
    Description: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Multiple Sclerosis Genetics Consortium -- Wellcome Trust Case Control Consortium 2 -- Sawcer, Stephen -- Hellenthal, Garrett -- Pirinen, Matti -- Spencer, Chris C A -- Patsopoulos, Nikolaos A -- Moutsianas, Loukas -- Dilthey, Alexander -- Su, Zhan -- Freeman, Colin -- Hunt, Sarah E -- Edkins, Sarah -- Gray, Emma -- Booth, David R -- Potter, Simon C -- Goris, An -- Band, Gavin -- Oturai, Annette Bang -- Strange, Amy -- Saarela, Janna -- Bellenguez, Celine -- Fontaine, Bertrand -- Gillman, Matthew -- Hemmer, Bernhard -- Gwilliam, Rhian -- Zipp, Frauke -- Jayakumar, Alagurevathi -- Martin, Roland -- Leslie, Stephen -- Hawkins, Stanley -- Giannoulatou, Eleni -- D'alfonso, Sandra -- Blackburn, Hannah -- Martinelli Boneschi, Filippo -- Liddle, Jennifer -- Harbo, Hanne F -- Perez, Marc L -- Spurkland, Anne -- Waller, Matthew J -- Mycko, Marcin P -- Ricketts, Michelle -- Comabella, Manuel -- Hammond, Naomi -- Kockum, Ingrid -- McCann, Owen T -- Ban, Maria -- Whittaker, Pamela -- Kemppinen, Anu -- Weston, Paul -- Hawkins, Clive -- Widaa, Sara -- Zajicek, John -- Dronov, Serge -- Robertson, Neil -- Bumpstead, Suzannah J -- Barcellos, Lisa F -- Ravindrarajah, Rathi -- Abraham, Roby -- Alfredsson, Lars -- Ardlie, Kristin -- Aubin, Cristin -- Baker, Amie -- Baker, Katharine -- Baranzini, Sergio E -- Bergamaschi, Laura -- Bergamaschi, Roberto -- Bernstein, Allan -- Berthele, Achim -- Boggild, Mike -- Bradfield, Jonathan P -- Brassat, David -- Broadley, Simon A -- Buck, Dorothea -- Butzkueven, Helmut -- Capra, Ruggero -- Carroll, William M -- Cavalla, Paola -- Celius, Elisabeth G -- Cepok, Sabine -- Chiavacci, Rosetta -- Clerget-Darpoux, Francoise -- Clysters, Katleen -- Comi, Giancarlo -- Cossburn, Mark -- Cournu-Rebeix, Isabelle -- Cox, Mathew B -- Cozen, Wendy -- Cree, Bruce A C -- Cross, Anne H -- Cusi, Daniele -- Daly, Mark J -- Davis, Emma -- de Bakker, Paul I W -- Debouverie, Marc -- D'hooghe, Marie Beatrice -- Dixon, Katherine -- Dobosi, Rita -- Dubois, Benedicte -- Ellinghaus, David -- Elovaara, Irina -- Esposito, Federica -- Fontenille, Claire -- Foote, Simon -- Franke, Andre -- Galimberti, Daniela -- Ghezzi, Angelo -- Glessner, Joseph -- Gomez, Refujia -- Gout, Olivier -- Graham, Colin -- Grant, Struan F A -- Guerini, Franca Rosa -- Hakonarson, Hakon -- Hall, Per -- Hamsten, Anders -- Hartung, Hans-Peter -- Heard, Rob N -- Heath, Simon -- Hobart, Jeremy -- Hoshi, Muna -- Infante-Duarte, Carmen -- Ingram, Gillian -- Ingram, Wendy -- Islam, Talat -- Jagodic, Maja -- Kabesch, Michael -- Kermode, Allan G -- Kilpatrick, Trevor J -- Kim, Cecilia -- Klopp, Norman -- Koivisto, Keijo -- Larsson, Malin -- Lathrop, Mark -- Lechner-Scott, Jeannette S -- Leone, Maurizio A -- Leppa, Virpi -- Liljedahl, Ulrika -- Bomfim, Izaura Lima -- Lincoln, Robin R -- Link, Jenny -- Liu, Jianjun -- Lorentzen, Aslaug R -- Lupoli, Sara -- Macciardi, Fabio -- Mack, Thomas -- Marriott, Mark -- Martinelli, Vittorio -- Mason, Deborah -- McCauley, Jacob L -- Mentch, Frank -- Mero, Inger-Lise -- Mihalova, Tania -- Montalban, Xavier -- Mottershead, John -- Myhr, Kjell-Morten -- Naldi, Paola -- Ollier, William -- Page, Alison -- Palotie, Aarno -- Pelletier, Jean -- Piccio, Laura -- Pickersgill, Trevor -- Piehl, Fredrik -- Pobywajlo, Susan -- Quach, Hong L -- Ramsay, Patricia P -- Reunanen, Mauri -- Reynolds, Richard -- Rioux, John D -- Rodegher, Mariaemma -- Roesner, Sabine -- Rubio, Justin P -- Ruckert, Ina-Maria -- Salvetti, Marco -- Salvi, Erika -- Santaniello, Adam -- Schaefer, Catherine A -- Schreiber, Stefan -- Schulze, Christian -- Scott, Rodney J -- Sellebjerg, Finn -- Selmaj, Krzysztof W -- Sexton, David -- Shen, Ling -- Simms-Acuna, Brigid -- Skidmore, Sheila -- Sleiman, Patrick M A -- Smestad, Cathrine -- Sorensen, Per Soelberg -- Sondergaard, Helle Bach -- Stankovich, Jim -- Strange, Richard C -- Sulonen, Anna-Maija -- Sundqvist, Emilie -- Syvanen, Ann-Christine -- Taddeo, Francesca -- Taylor, Bruce -- Blackwell, Jenefer M -- Tienari, Pentti -- Bramon, Elvira -- Tourbah, Ayman -- Brown, Matthew A -- Tronczynska, Ewa -- Casas, Juan P -- Tubridy, Niall -- Corvin, Aiden -- Vickery, Jane -- Jankowski, Janusz -- Villoslada, Pablo -- Markus, Hugh S -- Wang, Kai -- Mathew, Christopher G -- Wason, James -- Palmer, Colin N A -- Wichmann, H-Erich -- Plomin, Robert -- Willoughby, Ernest -- Rautanen, Anna -- Winkelmann, Juliane -- Wittig, Michael -- Trembath, Richard C -- Yaouanq, Jacqueline -- Viswanathan, Ananth C -- Zhang, Haitao -- Wood, Nicholas W -- Zuvich, Rebecca -- Deloukas, Panos -- Langford, Cordelia -- Duncanson, Audrey -- Oksenberg, Jorge R -- Pericak-Vance, Margaret A -- Haines, Jonathan L -- Olsson, Tomas -- Hillert, Jan -- Ivinson, Adrian J -- De Jager, Philip L -- Peltonen, Leena -- Stewart, Graeme J -- Hafler, David A -- Hauser, Stephen L -- McVean, Gil -- Donnelly, Peter -- Compston, Alastair -- 068545/Z/02/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084702/Wellcome Trust/United Kingdom -- 085475/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 898/Multiple Sclerosis Society/United Kingdom -- AI076544/AI/NIAID NIH HHS/ -- CA104021/CA/NCI NIH HHS/ -- G0100594/Medical Research Council/United Kingdom -- G0400017/Medical Research Council/United Kingdom -- G0700061/Medical Research Council/United Kingdom -- G0901310/Medical Research Council/United Kingdom -- G0901461/Medical Research Council/United Kingdom -- G19/2/Medical Research Council/United Kingdom -- K23N/S048869/PHS HHS/ -- NS032830/NS/NINDS NIH HHS/ -- NS049477/NS/NINDS NIH HHS/ -- NS049510/NS/NINDS NIH HHS/ -- NS067305/NS/NINDS NIH HHS/ -- NS19142/NS/NINDS NIH HHS/ -- NS26799/NS/NINDS NIH HHS/ -- NS43559/NS/NINDS NIH HHS/ -- PDA/02/06/016/Department of Health/United Kingdom -- R01 NS026799/NS/NINDS NIH HHS/ -- R01 NS049477/NS/NINDS NIH HHS/ -- R01 NS049477-06A1/NS/NINDS NIH HHS/ -- RR020092/RR/NCRR NIH HHS/ -- RR024992/RR/NCRR NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Aug 10;476(7359):214-9. doi: 10.1038/nature10251.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833088" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Differentiation/immunology ; Europe/ethnology ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Genome-Wide Association Study ; HLA-A Antigens/genetics ; HLA-DR Antigens/genetics ; HLA-DRB1 Chains ; Humans ; Immunity, Cellular/genetics/*immunology ; Major Histocompatibility Complex/genetics ; Multiple Sclerosis/*genetics/*immunology ; Polymorphism, Single Nucleotide/genetics ; Sample Size ; T-Lymphocytes, Helper-Inducer/cytology/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 20
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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