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  • 1
    Publication Date: 2018-11-02
    Description: Reconfiguration of nuclear structure and function during mitosis presents a significant challenge to resume the next cell cycle in the progeny cells without compromising structural and functional identity of the cells. Equally important is the requirement for cancer cells to retain the transformed phenotype, that is, unrestricted proliferative potential, suppression of cell phenotype, and activation of oncogenic pathways. Mitotic gene bookmarking retention of key regulatory proteins that include sequence-specific transcription factors, chromatin-modifying factors, and components of RNA Pol (RNAP) I and II regulatory machineries at gene loci on mitotic chromosomes plays key roles in coordinate control of cell phenotype, growth, and proliferation postmitotically. There is growing recognition that three distinct protein types, mechanistically, play obligatory roles in mitotic gene bookmarking: (i) Retention of phenotypic transcription factors on mitotic chromosomes is essential to sustain lineage commitment; (ii) Select chromatin modifiers and posttranslational histone modifications/variants retain competency of mitotic chromatin for gene reactivation as cells exit mitosis; and (iii) Functional components of RNAP I and II transcription complexes (e.g., UBF and TBP, respectively) are retained on genes poised for reactivation immediately following mitosis. Importantly, recent findings have identified oncogenes that are associated with target genes on mitotic chromosomes in cancer cells. The current review proposes that mitotic gene bookmarking is an extensively utilized epigenetic mechanism for stringent control of proliferation and identity in normal cells and hypothesizes that bookmarking plays a pivotal role in maintenance of tumor phenotypes, that is, unrestricted proliferation and compromised control of differentiation. Mol Cancer Res; 16(11); 1617–24. ©2018 AACR .
    Print ISSN: 1541-7786
    Electronic ISSN: 1557-3125
    Topics: Medicine
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  • 2
    Publication Date: 2018-04-03
    Description: Aggressive breast cancer is difficult to treat as it is unresponsive to many hormone-based therapies; therefore, it is imperative to identify novel, targetable regulators of progression. Long non-coding RNAs (lncRNA) are important regulators in breast cancer and have great potential as therapeutic targets; however, little is known about how the majority of lncRNAs function within breast cancer. This study characterizes a novel lncRNA, MANCR (mitotically-associated long noncoding RNA; LINC00704), which is upregulated in breast cancer patient specimens and cells. Depletion of MANCR in triple-negative breast cancer cells significantly decreases cell proliferation and viability, with concomitant increases in DNA damage. Transcriptome analysis, based on RNA sequencing, following MANCR knockdown reveals significant differences in the expression of 〉2,000 transcripts, and gene set enrichment analysis identifies changes in multiple categories related to cell-cycle regulation. Furthermore, MANCR expression is highest in mitotic cells by both RT-qPCR and RNA in situ hybridization. Consistent with a role in cell-cycle regulation, MANCR-depleted cells have a lower mitotic index and higher incidences of defective cytokinesis and cell death. Taken together, these data reveal a role for the novel lncRNA, MANCR, in genomic stability of aggressive breast cancer, and identify it as a potential therapeutic target. Implications: The novel lncRNA, MANCR (LINC00704), is upregulated in breast cancer and is functionally linked with cell proliferation, viability, and genomic stability. Mol Cancer Res; 16(4); 587–98. ©2018 AACR .
    Print ISSN: 1541-7786
    Electronic ISSN: 1557-3125
    Topics: Medicine
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  • 3
    Publication Date: 2015-01-22
    Description: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393366/" 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/PMC4393366/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hibar, Derrek P -- Stein, Jason L -- Renteria, Miguel E -- Arias-Vasquez, Alejandro -- Desrivieres, Sylvane -- Jahanshad, Neda -- Toro, Roberto -- Wittfeld, Katharina -- Abramovic, Lucija -- Andersson, Micael -- Aribisala, Benjamin S -- Armstrong, Nicola J -- Bernard, Manon -- Bohlken, Marc M -- Boks, Marco P -- Bralten, Janita -- Brown, Andrew A -- Chakravarty, M Mallar -- Chen, Qiang -- Ching, Christopher R K -- Cuellar-Partida, Gabriel -- den Braber, Anouk -- Giddaluru, Sudheer -- Goldman, Aaron L -- Grimm, Oliver -- Guadalupe, Tulio -- Hass, Johanna -- Woldehawariat, Girma -- Holmes, Avram J -- Hoogman, Martine -- Janowitz, Deborah -- Jia, Tianye -- Kim, Sungeun -- Klein, Marieke -- Kraemer, Bernd -- Lee, Phil H -- Olde Loohuis, Loes M -- Luciano, Michelle -- Macare, Christine -- Mather, Karen A -- Mattheisen, Manuel -- Milaneschi, Yuri -- Nho, Kwangsik -- Papmeyer, Martina -- Ramasamy, Adaikalavan -- Risacher, Shannon L -- Roiz-Santianez, Roberto -- Rose, Emma J -- Salami, Alireza -- Samann, Philipp G -- Schmaal, Lianne -- Schork, Andrew J -- Shin, Jean -- Strike, Lachlan T -- Teumer, Alexander -- van Donkelaar, Marjolein M J -- van Eijk, Kristel R -- Walters, Raymond K -- Westlye, Lars T -- Whelan, Christopher D -- Winkler, Anderson M -- Zwiers, Marcel P -- Alhusaini, Saud -- Athanasiu, Lavinia -- Ehrlich, Stefan -- Hakobjan, Marina M H -- Hartberg, Cecilie B -- Haukvik, Unn K -- Heister, Angelien J G A M -- Hoehn, David -- Kasperaviciute, Dalia -- Liewald, David C M -- Lopez, Lorna M -- Makkinje, Remco R R -- Matarin, Mar -- Naber, Marlies A M -- McKay, D Reese -- Needham, Margaret -- Nugent, Allison C -- Putz, Benno -- Royle, Natalie A -- Shen, Li -- Sprooten, Emma -- Trabzuni, Daniah -- van der Marel, Saskia S L -- van Hulzen, Kimm J E -- Walton, Esther -- Wolf, Christiane -- Almasy, Laura -- Ames, David -- Arepalli, Sampath -- Assareh, Amelia A -- Bastin, Mark E -- Brodaty, Henry -- Bulayeva, Kazima B -- Carless, Melanie A -- Cichon, Sven -- Corvin, Aiden -- Curran, Joanne E -- Czisch, Michael -- de Zubicaray, Greig I -- Dillman, Allissa -- Duggirala, Ravi -- Dyer, Thomas D -- Erk, Susanne -- Fedko, Iryna O -- Ferrucci, Luigi -- Foroud, Tatiana M -- Fox, Peter T -- Fukunaga, Masaki -- Gibbs, J Raphael -- Goring, Harald H H -- Green, Robert C -- Guelfi, Sebastian -- Hansell, Narelle K -- Hartman, Catharina A -- Hegenscheid, Katrin -- Heinz, Andreas -- Hernandez, Dena G -- Heslenfeld, Dirk J -- Hoekstra, Pieter J -- Holsboer, Florian -- Homuth, Georg -- Hottenga, Jouke-Jan -- Ikeda, Masashi -- Jack, Clifford R Jr -- Jenkinson, Mark -- Johnson, Robert -- Kanai, Ryota -- Keil, Maria -- Kent, Jack W Jr -- Kochunov, Peter -- Kwok, John B -- Lawrie, Stephen M -- Liu, Xinmin -- Longo, Dan L -- McMahon, Katie L -- Meisenzahl, Eva -- Melle, Ingrid -- Mohnke, Sebastian -- Montgomery, Grant W -- Mostert, Jeanette C -- Muhleisen, Thomas W -- Nalls, Michael A -- Nichols, Thomas E -- Nilsson, Lars G -- Nothen, Markus M -- Ohi, Kazutaka -- Olvera, Rene L -- Perez-Iglesias, Rocio -- Pike, G Bruce -- Potkin, Steven G -- Reinvang, Ivar -- Reppermund, Simone -- Rietschel, Marcella -- Romanczuk-Seiferth, Nina -- Rosen, Glenn D -- Rujescu, Dan -- Schnell, Knut -- Schofield, Peter R -- Smith, Colin -- Steen, Vidar M -- Sussmann, Jessika E -- Thalamuthu, Anbupalam -- Toga, Arthur W -- Traynor, Bryan J -- Troncoso, Juan -- Turner, Jessica A -- Valdes Hernandez, Maria C -- van 't Ent, Dennis -- van der Brug, Marcel -- van der Wee, Nic J A -- van Tol, Marie-Jose -- Veltman, Dick J -- Wassink, Thomas H -- Westman, Eric -- Zielke, Ronald H -- Zonderman, Alan B -- Ashbrook, David G -- Hager, Reinmar -- Lu, Lu -- McMahon, Francis J -- Morris, Derek W -- Williams, Robert W -- Brunner, Han G -- Buckner, Randy L -- Buitelaar, Jan K -- Cahn, Wiepke -- Calhoun, Vince D -- Cavalleri, Gianpiero L -- Crespo-Facorro, Benedicto -- Dale, Anders M -- Davies, Gareth E -- Delanty, Norman -- Depondt, Chantal -- Djurovic, Srdjan -- Drevets, Wayne C -- Espeseth, Thomas -- Gollub, Randy L -- Ho, Beng-Choon -- Hoffmann, Wolfgang -- Hosten, Norbert -- Kahn, Rene S -- Le Hellard, Stephanie -- Meyer-Lindenberg, Andreas -- Muller-Myhsok, Bertram -- Nauck, Matthias -- Nyberg, Lars -- Pandolfo, Massimo -- Penninx, Brenda W J H -- Roffman, Joshua L -- Sisodiya, Sanjay M -- Smoller, Jordan W -- van Bokhoven, Hans -- van Haren, Neeltje E M -- Volzke, Henry -- Walter, Henrik -- Weiner, Michael W -- Wen, Wei -- White, Tonya -- Agartz, Ingrid -- Andreassen, Ole A -- Blangero, John -- Boomsma, Dorret I -- Brouwer, Rachel M -- Cannon, Dara M -- Cookson, Mark R -- de Geus, Eco J C -- Deary, Ian J -- Donohoe, Gary -- Fernandez, Guillen -- Fisher, Simon E -- Francks, Clyde -- Glahn, David C -- Grabe, Hans J -- Gruber, Oliver -- Hardy, John -- Hashimoto, Ryota -- Hulshoff Pol, Hilleke E -- Jonsson, Erik G -- Kloszewska, Iwona -- Lovestone, Simon -- Mattay, Venkata S -- Mecocci, Patrizia -- McDonald, Colm -- McIntosh, Andrew M -- Ophoff, Roel A -- Paus, Tomas -- Pausova, Zdenka -- Ryten, Mina -- Sachdev, Perminder S -- Saykin, Andrew J -- Simmons, Andy -- Singleton, Andrew -- Soininen, Hilkka -- Wardlaw, Joanna M -- Weale, Michael E -- Weinberger, Daniel R -- Adams, Hieab H H -- Launer, Lenore J -- Seiler, Stephan -- Schmidt, Reinhold -- Chauhan, Ganesh -- Satizabal, Claudia L -- Becker, James T -- Yanek, Lisa -- van der Lee, Sven J -- Ebling, Maritza -- Fischl, Bruce -- Longstreth, W T Jr -- Greve, Douglas -- Schmidt, Helena -- Nyquist, Paul -- Vinke, Louis N -- van Duijn, Cornelia M -- Xue, Luting -- Mazoyer, Bernard -- Bis, Joshua C -- Gudnason, Vilmundur -- Seshadri, Sudha -- Ikram, M Arfan -- Alzheimer's Disease Neuroimaging Initiative -- CHARGE Consortium -- EPIGEN -- IMAGEN -- SYS -- Martin, Nicholas G -- Wright, Margaret J -- Schumann, Gunter -- Franke, Barbara -- Thompson, Paul M -- Medland, Sarah E -- 100309/Wellcome Trust/United Kingdom -- 104036/Wellcome Trust/United Kingdom -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0701120/Medical Research Council/United Kingdom -- G1001245/Medical Research Council/United Kingdom -- K99 LM011384/LM/NLM NIH HHS/ -- K99 MH101367/MH/NIMH NIH HHS/ -- MR/K026992/1/Medical Research Council/United Kingdom -- P41 EB015922/EB/NIBIB NIH HHS/ -- P50 AG005133/AG/NIA NIH HHS/ -- P50 AG005134/AG/NIA NIH HHS/ -- P50 AG005146/AG/NIA NIH HHS/ -- R00 LM011384/LM/NLM NIH HHS/ -- R01 AG040060/AG/NIA NIH HHS/ -- R01 EB015611/EB/NIBIB NIH HHS/ -- RF1 AG041915/AG/NIA NIH HHS/ -- U01 AG049505/AG/NIA NIH HHS/ -- U24 AG021886/AG/NIA NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- UL1 TR001108/TR/NCATS NIH HHS/ -- UL1 TR001120/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Apr 9;520(7546):224-9. doi: 10.1038/nature14101. Epub 2015 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. ; 1] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. [2] Neurogenetics Program, Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095, USA. ; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [4] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK. ; 1] Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur, Paris 75015, France. [2] Centre Nationale de Recherche Scientifique (CNRS) Unite de Recherche Associee (URA) 2182 Genes, Synapses and Cognition, Institut Pasteur, Paris 75015, France. [3] Universite Paris Diderot, Sorbonne Paris Cite, Paris 75015, France. ; 1] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany. [2] Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. ; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. ; Umea Centre for Functional Brain Imaging (UFBI), Umea University, Umea 901 87, Sweden. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Department of Computer Science, Lagos State University, Lagos, Nigeria. [3] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. [2] School of Mathematics and Statistics, University of Sydney, Sydney 2006, Australia. ; The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway. ; 1] Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal H4H 1R3, Canada. [2] Department of Psychiatry and Biomedical Engineering, McGill University, Montreal H3A 2B4, Canada. ; Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. ; 1] Imaging Genetics Center, Institute for Neuroimaging &Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90292, USA. [2] Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, California 90095, USA. ; Biological Psychology, Neuroscience Campus Amsterdam &EMGO Institute for Health and Care Research, VU University &VU Medical Center, Amsterdam 1081 BT, The Netherlands. ; 1] NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. [2] Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway. ; Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim 68159, Germany. ; 1] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands. [2] International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands. ; Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany. ; Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. ; 1] Department of Psychology, Yale University, New Haven, Connecticut 06511, USA. [2] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [3] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA. [4] Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. ; Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. ; 1] Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark. [2] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen DK-8000, Denmark. [3] Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus DK-8000, Denmark. ; Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands. ; Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. ; 1] Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. [2] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Department of Psychiatry, University Hospital Marques de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander 39008, Spain. [2] Cibersam (Centro Investigacion Biomedica en Red Salud Mental), Madrid 28029, Spain. ; 1] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. [2] Center for Translational Research on Adversity, Neurodevelopment and Substance Abuse (C-TRANS), Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21045, USA. ; 1] Umea Centre for Functional Brain Imaging (UFBI), Umea University, Umea 901 87, Sweden. [2] Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden. ; Max Planck Institute of Psychiatry, Munich 80804, Germany. ; 1] Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA. [2] Department of Cognitive Sciences, University of California, San Diego, California 92161, USA. ; 1] QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. [2] School of Psychology, University of Queensland, Brisbane 4072, Australia. [3] Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia. ; Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany. ; 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Boston, Massachusetts 02142, USA. ; 1] NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway. [2] Department of Psychology, University of Oslo, Oslo 0373, Norway. ; 1] The Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, Oxford University, Oxford OX3 9DU, UK. [2] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. ; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada. ; 1] Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden 01307 Germany. [2] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway. ; NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. ; 1] UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK. [2] Department of Medicine, Imperial College London, London W12 0NN, UK. ; Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK. ; 1] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. [2] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA. ; Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [3] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; 1] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. [2] Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA. [3] Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. ; 1] Texas Biomedical Research Institute, San Antonio, Texas 78245, USA. [2] University of Texas Health Science Center, San Antonio, Texas 78229, USA. ; 1] National Ageing Research Institute, Royal Melbourne Hospital, Melbourne 3052, Australia. [2] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. [2] Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. [3] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [4] Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia. ; Texas Biomedical Research Institute, San Antonio, Texas 78245, USA. ; 1] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel 4055, Switzerland. [2] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Julich, D-52425, Germany. [4] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; School of Psychology, University of Queensland, Brisbane 4072, Australia. ; Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, CCM, Berlin 10117, Germany. ; Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA. ; 1] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] University of Texas Health Science Center, San Antonio, Texas 78229, USA. [2] South Texas Veterans Health Care System, San Antonio, Texas 78229, USA. ; Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. ; Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands. ; Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; Departments of Cognitive and Clinical Neuropsychology, VU University Amsterdam, 1081 BT Amsterdam, The Netherlands. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17489, Germany. ; Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. ; Radiology, Mayo Clinic, Rochester, Minnesota 55905, USA. ; FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK. ; NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA. ; 1] School of Psychology, University of Sussex, Brighton BN1 9QH, UK. [2] Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK. ; Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA. ; 1] Neuroscience Research Australia, Sydney 2031, Australia. [2] School of Medical Sciences, UNSW, Sydney 2052, Australia. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA. ; Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. ; Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia. ; Department of Psychiatry, Ludwig-Maximilians-Universitat, Munich 80336, Germany. ; 1] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [2] Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Julich, D-52425, Germany. [3] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; 1] FMRIB Centre, University of Oxford, Oxford OX3 9DU, UK. [2] Department of Statistics &WMG, University of Warwick, Coventry CV4 7AL, UK. ; 1] Institute of Human Genetics, University of Bonn, Bonn, D-53127, Germany. [2] Department of Genomics, Life &Brain Center, University of Bonn, Bonn D-53127, Germany. ; Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Cibersam (Centro Investigacion Biomedica en Red Salud Mental), Madrid 28029, Spain. [2] Institute of Psychiatry, King's College London, London SE5 8AF, UK. ; 1] Department of Neurology, University of Calgary, Calgary T2N 2T9, Canada. [2] Department of Clinical Neuroscience, University of Calgary, Calgary T2N 2T9, Canada. ; Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA. ; Department of Psychology, University of Oslo, Oslo 0373, Norway. ; 1] Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. [2] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of General Psychiatry, Heidelberg University Hospital, Heidelberg 69115, Germany. ; Department of Neuropathology, MRC Sudden Death Brain Bank Project, University of Edinburgh, Edinburgh EH8 9AG, UK. ; Laboratory of Neuro Imaging, Institute for Neuroimaging and Informatics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. ; Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, USA. ; Psychology Department and Neuroscience Institute, Georgia State University, Atlanta, Georgia 30302, USA. ; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Genentech, South San Francisco, California 94080, USA. ; Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. ; Neuroimaging Centre, University of Groningen, University Medical Center Groningen, Groningen 9713 AW, The Netherlands. ; Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden. ; Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA. ; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. ; 1] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [2] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [3] Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China. ; 1] Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. [2] Cognitive Genetics and Therapy Group, School of Psychology &Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland. ; 1] Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. [2] Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [3] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Department of Psychology, Center for Brain Science, Harvard University, Boston, Massachusetts 02138, USA. ; 1] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [3] Karakter Child and Adolescent Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. ; 1] The Mind Research Network &LBERI, Albuquerque, New Mexico 87106, USA. [2] Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA. ; 1] Center for Translational Imaging and Personalized Medicine, University of California, San Diego, California 92093, USA. [2] Departments of Neurosciences, Radiology, Psychiatry, and Cognitive Science, University of California, San Diego, California 92093, USA. ; Avera Institute for Human Genetics, Sioux Falls, South Dakota, 57108, USA. ; 1] Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland. [2] Neurology Division, Beaumont Hospital, Dublin 9, Ireland. ; Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Janssen Research &Development, Johnson &Johnson, Titusville, New Jersey 08560, USA. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [3] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA. ; 1] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany. [2] Institute for Community Medicine, University Medicine Greifswald, Greifswald D-17475, Germany. ; 1] Max Planck Institute of Psychiatry, Munich 80804, Germany. [2] Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany. [3] University of Liverpool, Institute of Translational Medicine, Liverpool L69 3BX, UK. ; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. ; UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK. ; 1] Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [2] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02115, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Boston, Massachusetts 02141, USA. [4] Harvard Medical School, Boston, Massachusetts 02115, USA. ; Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center, University of California, San Francisco, California 94121, USA. ; 1] Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands. [2] Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway. [3] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden. ; 1] Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA. [2] Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ; 1] Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. ; 1] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands. [2] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands. ; 1] Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany. [2] Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund 18435, Germany. ; 1] Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany. [2] Max Planck Institute of Psychiatry, Munich 80804, Germany. ; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan. ; 1] NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway. [2] Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm SE-171 76, Sweden. ; Medical University of Lodz, Lodz 90-419, Poland. ; 1] Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK. [2] NIHR Dementia Biomedical Research Unit, King's College London, London SE5 8AF, UK. ; 1] Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia 06156, Italy. ; Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. ; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. [2] Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK. ; 1] Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. [2] Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. ; 1] Rotman Research Institute, University of Toronto, Toronto M6A 2E1, Canada. [2] Departments of Psychology and Psychiatry, University of Toronto, Toronto M5T 1R8, Canada. ; 1] The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada. [2] Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto M5S 3E2, Canada. ; 1] Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. [2] Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. ; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia. [2] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney 2031, Australia. ; 1] Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [2] Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. [3] Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, CCM, Berlin 10117, Germany. ; 1] Department of Neuroimaging, Institute of Psychiatry, King's College London, London SE5 8AF, UK. [2] Biomedical Research Centre for Mental Health, King's College London, London SE5 8AF, UK. [3] Biomedical Research Unit for Dementia, King's College London, London SE5 8AF, UK. ; 1] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio FI-70211, Finland. [2] Neurocentre Neurology, Kuopio University Hospital, Kuopio FI-70211, Finland. ; Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK. ; 1] Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA. [2] Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; 1] Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. [2] Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland 20892, USA. ; Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria. ; INSERM U897, University of Bordeaux, Bordeaux 33076, France. ; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [2] Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; 1] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. [2] Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. [3] Department of Psychology, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ; General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Epidemiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands. ; 1] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [2] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] The Athinoula A.Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. [2] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. [3] Computer Science and AI Lab, Massachusetts Institute of Technology, Boston, Massachusetts 02141, USA. ; Department of Neurology University of Washington, Seattle, Washington 98195, USA. ; Institute of Molecular Biology and Biochemistry, Medical University Graz, 8010 Graz, Austria. ; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Groupe d'Imagerie Neurofonctionnelle, UMR5296 CNRS, CEA and University of Bordeaux, Bordeaux 33076, France. ; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington 98101, USA. ; Icelandic Heart Association, University of Iceland, Faculty of Medicine, Reykjavik 101, Iceland. ; 1] Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. [2] Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ; 1] QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. [2] School of Psychology, University of Queensland, Brisbane 4072, Australia. ; 1] Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [2] Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands. [3] Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen 6500 GL, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25607358" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/genetics ; Apoptosis/genetics ; Brain/*anatomy & histology ; Caudate Nucleus/anatomy & histology ; Child ; Female ; Gene Expression Regulation, Developmental/genetics ; Genetic Loci/genetics ; Genetic Variation/*genetics ; *Genome-Wide Association Study ; Hippocampus/anatomy & histology ; Humans ; Magnetic Resonance Imaging ; Male ; Membrane Proteins/genetics ; Middle Aged ; Organ Size/genetics ; Putamen/anatomy & histology ; Sex Characteristics ; Skull/anatomy & histology ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-04-06
    Description: A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784322/" 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/PMC3784322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Apps, Richard -- Qi, Ying -- Carlson, Jonathan M -- Chen, Haoyan -- Gao, Xiaojiang -- Thomas, Rasmi -- Yuki, Yuko -- Del Prete, Greg Q -- Goulder, Philip -- Brumme, Zabrina L -- Brumme, Chanson J -- John, Mina -- Mallal, Simon -- Nelson, George -- Bosch, Ronald -- Heckerman, David -- Stein, Judy L -- Soderberg, Kelly A -- Moody, M Anthony -- Denny, Thomas N -- Zeng, Xue -- Fang, Jingyuan -- Moffett, Ashley -- Lifson, Jeffrey D -- Goedert, James J -- Buchbinder, Susan -- Kirk, Gregory D -- Fellay, Jacques -- McLaren, Paul -- Deeks, Steven G -- Pereyra, Florencia -- Walker, Bruce -- Michael, Nelson L -- Weintrob, Amy -- Wolinsky, Steven -- Liao, Wilson -- Carrington, Mary -- 5-M01-RR-00722/RR/NCRR NIH HHS/ -- HHSN261200800001E/CA/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- K08 AR057763/AR/NIAMS NIH HHS/ -- K08AR057763/AR/NIAMS NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- N02-CP-55504/CP/NCI NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-24/AI/NIAID NIH HHS/ -- P30 MH62246/MH/NIMH NIH HHS/ -- PG/09/077/27964/British Heart Foundation/United Kingdom -- R01 AI046995/AI/NIAID NIH HHS/ -- R01 AI060460/AI/NIAID NIH HHS/ -- R01 AI087145/AI/NIAID NIH HHS/ -- R01 AR065174/AR/NIAMS NIH HHS/ -- R01-AI046995/AI/NIAID NIH HHS/ -- R01-AI060460/AI/NIAID NIH HHS/ -- R01-DA-04334/DA/NIDA NIH HHS/ -- R01-DA-12568/DA/NIDA NIH HHS/ -- R01-DA04334/DA/NIDA NIH HHS/ -- R01-DA12568/DA/NIDA NIH HHS/ -- R24 AI067039/AI/NIAID NIH HHS/ -- U01-AI-067854/AI/NIAID NIH HHS/ -- U01-AI-35039/AI/NIAID NIH HHS/ -- U01-AI-35040/AI/NIAID NIH HHS/ -- U01-AI-35041/AI/NIAID NIH HHS/ -- U01-AI-35042/AI/NIAID NIH HHS/ -- U01-AI-35043/AI/NIAID NIH HHS/ -- U01-AI-37613/AI/NIAID NIH HHS/ -- U01-AI-37984/AI/NIAID NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):87-91. doi: 10.1126/science.1232685.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer and Inflammation Program, Laboratory of Experimental Immunology, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559252" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/genetics ; Alleles ; Amino Acid Sequence ; Anti-Retroviral Agents/therapeutic use ; Crohn Disease/genetics/immunology ; *Gene Expression Regulation ; HIV/genetics/*immunology ; HIV Infections/drug therapy/*genetics/*immunology ; HLA-C Antigens/*genetics ; Humans ; Immunodominant Epitopes/genetics ; Molecular Sequence Data ; Mutation ; Peptide Fragments/immunology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Load/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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  • 5
    Publication Date: 2012-04-13
    Description: Multiple studies have confirmed the contribution of rare de novo copy number variations to the risk for autism spectrum disorders. But whereas de novo single nucleotide variants have been identified in affected individuals, their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations have not been well characterized in matched unaffected controls, and such data are vital to the interpretation of de novo coding mutations observed in probands. Here we show, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects. On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in the same gene among unrelated probands reliably identifies risk alleles, providing a clear path forward for gene discovery. Among a total of 279 identified de novo coding mutations, there is a single instance in probands, and none in siblings, in which two independent nonsense variants disrupt the same gene, SCN2A (sodium channel, voltage-gated, type II, alpha subunit), a result that is highly unlikely by chance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667984/" 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/PMC3667984/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanders, Stephan J -- Murtha, Michael T -- Gupta, Abha R -- Murdoch, John D -- Raubeson, Melanie J -- Willsey, A Jeremy -- Ercan-Sencicek, A Gulhan -- DiLullo, Nicholas M -- Parikshak, Neelroop N -- Stein, Jason L -- Walker, Michael F -- Ober, Gordon T -- Teran, Nicole A -- Song, Youeun -- El-Fishawy, Paul -- Murtha, Ryan C -- Choi, Murim -- Overton, John D -- Bjornson, Robert D -- Carriero, Nicholas J -- Meyer, Kyle A -- Bilguvar, Kaya -- Mane, Shrikant M -- Sestan, Nenad -- Lifton, Richard P -- Gunel, Murat -- Roeder, Kathryn -- Geschwind, Daniel H -- Devlin, Bernie -- State, Matthew W -- K08 MH087639/MH/NIMH NIH HHS/ -- R25 MH077823/MH/NIMH NIH HHS/ -- T32 GM008042/GM/NIGMS NIH HHS/ -- U01 MH081896/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Apr 4;485(7397):237-41. doi: 10.1038/nature10945.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program on Neurogenetics, Child Study Center, Department of Psychiatry, Yale University School of Medicine, 230 South Frontage Road, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22495306" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Autistic Disorder/*genetics ; Codon, Nonsense/genetics ; Exome/*genetics ; Exons/*genetics ; Genetic Heterogeneity ; Genetic Predisposition to Disease/*genetics ; Humans ; Mutation/*genetics ; NAV1.2 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins/*genetics ; RNA Splice Sites/genetics ; Siblings ; Sodium Channels/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 14 (1975), S. 1859-1866 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Exponentially growing HeLa S3 cells were labelled for 48 h with 3H-glucosamine (1 ui ml-1) and three nuclear preparations were isolated. Nuclei containing intact nuclear envelopes as well as some adhering cytoplasm (crude nuclei) were prepared by osmotically swelling cells in 10 mM KC1, 1.5 mM ...
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  • 10
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In vitro 32P-labelled 7-1 IS polysomal RNA from S phase HeLa cells was electrophoresed under denaturing conditions in a 6% (w/v) acrylamide-8.3M urea gel at 55-60 C (Fig. la), and the three RNA bands (A, B, and C) in the H4 region were excised from the gel, and the RNA eluted. When each of these H4 ...
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