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  • 1
    Publication Date: 2010-09-10
    Description: Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-a macrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 x 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 x 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657719/" 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/PMC3657719/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinig, Matthias -- Petretto, Enrico -- Wallace, Chris -- Bottolo, Leonardo -- Rotival, Maxime -- Lu, Han -- Li, Yoyo -- Sarwar, Rizwan -- Langley, Sarah R -- Bauerfeind, Anja -- Hummel, Oliver -- Lee, Young-Ae -- Paskas, Svetlana -- Rintisch, Carola -- Saar, Kathrin -- Cooper, Jason -- Buchan, Rachel -- Gray, Elizabeth E -- Cyster, Jason G -- Cardiogenics Consortium -- Erdmann, Jeanette -- Hengstenberg, Christian -- Maouche, Seraya -- Ouwehand, Willem H -- Rice, Catherine M -- Samani, Nilesh J -- Schunkert, Heribert -- Goodall, Alison H -- Schulz, Herbert -- Roider, Helge G -- Vingron, Martin -- Blankenberg, Stefan -- Munzel, Thomas -- Zeller, Tanja -- Szymczak, Silke -- Ziegler, Andreas -- Tiret, Laurence -- Smyth, Deborah J -- Pravenec, Michal -- Aitman, Timothy J -- Cambien, Francois -- Clayton, David -- Todd, John A -- Hubner, Norbert -- Cook, Stuart A -- 061858/Wellcome Trust/United Kingdom -- 076113/Wellcome Trust/United Kingdom -- 089989/Wellcome Trust/United Kingdom -- MC_U120061454/Medical Research Council/United Kingdom -- MC_U120085815/Medical Research Council/United Kingdom -- MC_U120097112/Medical Research Council/United Kingdom -- P301/10/0290/British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Sep 23;467(7314):460-4. doi: 10.1038/nature09386. Epub 2010 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Delbruck-Center for Molecular Medicine (MDC), Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20827270" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromosomes, Human, Pair 13/genetics ; Chromosomes, Mammalian/genetics ; Diabetes Mellitus, Type 1/*genetics/immunology ; Gene Regulatory Networks/genetics ; Genetic Loci/*genetics ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Humans ; Immunity, Innate/*genetics ; Inflammation/genetics/immunology ; Interferon Regulatory Factor-7/immunology ; Macrophages/immunology/metabolism ; Organ Specificity ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Rats ; Receptors, G-Protein-Coupled/genetics/metabolism ; Viruses/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchan, J Ross -- Parker, Roy -- New York, N.Y. -- Science. 2007 Dec 21;318(5858):1877-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, University of Arizona, Tucson, AZ 85721, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18096794" target="_blank"〉PubMed〈/a〉
    Keywords: *3' Untranslated Regions ; Animals ; Cell Cycle ; *Gene Expression Regulation ; Humans ; MicroRNAs/*metabolism ; *Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/metabolism ; Tumor Necrosis Factor-alpha/biosynthesis/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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  • 3
    Publication Date: 2011-10-08
    Description: Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-alpha and PGC1alpha (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189541/" 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/PMC3189541/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDermott-Roe, Chris -- Ye, Junmei -- Ahmed, Rizwan -- Sun, Xi-Ming -- Serafin, Anna -- Ware, James -- Bottolo, Leonardo -- Muckett, Phil -- Canas, Xavier -- Zhang, Jisheng -- Rowe, Glenn C -- Buchan, Rachel -- Lu, Han -- Braithwaite, Adam -- Mancini, Massimiliano -- Hauton, David -- Marti, Ramon -- Garcia-Arumi, Elena -- Hubner, Norbert -- Jacob, Howard -- Serikawa, Tadao -- Zidek, Vaclav -- Papousek, Frantisek -- Kolar, Frantisek -- Cardona, Maria -- Ruiz-Meana, Marisol -- Garcia-Dorado, David -- Comella, Joan X -- Felkin, Leanne E -- Barton, Paul J R -- Arany, Zoltan -- Pravenec, Michal -- Petretto, Enrico -- Sanchis, Daniel -- Cook, Stuart A -- 087183/Wellcome Trust/United Kingdom -- MC_U120085815/Medical Research Council/United Kingdom -- MC_U120097112/Medical Research Council/United Kingdom -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Oct 5;478(7367):114-8. doi: 10.1038/nature10490.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21979051" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Body Weight/genetics ; Cardiomegaly/*enzymology/genetics/*pathology/physiopathology ; Cell Respiration ; Chromosomes, Mammalian/genetics ; Crosses, Genetic ; Endodeoxyribonucleases/deficiency/genetics/*metabolism ; Female ; Gene Expression Regulation ; Genes, Mitochondrial/genetics ; Hypertrophy, Left Ventricular/enzymology/genetics/pathology/physiopathology ; Lipid Metabolism ; Male ; Mitochondria/genetics/*metabolism/pathology ; Organ Size/genetics ; Quantitative Trait Loci/genetics ; RNA-Binding Proteins/metabolism ; Rats ; Rats, Inbred Strains ; Reactive Oxygen Species/metabolism ; Receptors, Estrogen/metabolism ; Transcription Factors/metabolism
    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: 1964-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 27 (1981), S. 338-343 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 6
    Publication Date: 1981-07-01
    Print ISSN: 0007-4861
    Electronic ISSN: 1432-0800
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Published by Springer
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  • 7
    Publication Date: 1995-02-01
    Print ISSN: 1047-4838
    Electronic ISSN: 1543-1851
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Springer
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  • 8
    Publication Date: 1970-12-01
    Print ISSN: 0361-0128
    Electronic ISSN: 1554-0774
    Topics: Geosciences
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  • 9
    Publication Date: 1974-05-01
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley on behalf of American Cancer Society.
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  • 10
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    Unknown
    In:  Other Sources
    Publication Date: 2011-08-19
    Description: The use of dictionaries and thesauri in information retrieval is discussed. The structure and functions of thesauri and dictionaries are described. Particular attention is given to the format of the NASA Thesaurus. The relationship between thesauri and dictionaries, the need to regularize terminology, and the capitalization of words are examined.
    Keywords: DOCUMENTATION AND INFORMATION SCIENCE
    Type: Information Services and Use (ISSN 0167-5265); 9, 19
    Format: text
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