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Sökning: onr:"swepub:oai:DiVA.org:oru-51667" > A protein-truncatin...

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

Rivas, Manuel A. (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Graham, Daniel (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA;
Sulem, Patrick (författare)
deCODE Genetics, Amgen Inc., Reykjavik, Iceland
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Stevens, Christine (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA;
Desch, A. Nicole (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA;
Goyette, Philippe (författare)
Research Center, Montreal Heart Institute, Montréal, Québec, Canada
Gudbjartsson, Daniel (författare)
deCODE Genetics, Amgen Inc., Reykjavik, Iceland; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland
Jonsdottir, Ingileif (författare)
deCODE Genetics, Amgen Inc., Reykjavik, Iceland; Department of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Thorsteinsdottir, Unnur (författare)
deCODE Genetics, Amgen Inc., Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Degenhardt, Frauke (författare)
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
Mucha, Sören (författare)
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
Kurki, Mitja I. (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Li, Dalin (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA; Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, USA
D'Amato, Mauro (författare)
Karolinska Institutet
Annese, Vito (författare)
Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, San Giovanni Rotondo, Italy
Vermeire, Severine (författare)
Department of Clinical and Experimental Medicine, Translational Research in GastroIntestinal Disorders (TARGID), Katholieke Universiteit (KU) Leuven, Leuven, Belgium; Division of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium
Weersma, Rinse K. (författare)
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands; Department of Gastroenterology and Hepatology, University of Groningen, Groningen, The Netherlands
Halfvarson, Jonas, 1970- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden
Paavola-Sakki, Paulina (författare)
Department of Medicine, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland; Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
Lappalainen, Maarit (författare)
Department of Medicine, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland; Research Programs Unit, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland;
Lek, Monkol (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Cummings, Beryl (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Tukiainen, Taru (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Haritunians, Talin (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA; Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, USA
Halme, Leena (författare)
Department of Transplantation and Liver Surgery, University of Helsinki, Helsinki, Finland
Koskinen, Lotta L. E. (författare)
Research Programs Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
Ananthakrishnan, Ashwin N. (författare)
Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA; Division of Medical Sciences, Harvard Medical School, Boston, USA
Luo, Yang (författare)
Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Hinxton, UK
Heap, Graham A. (författare)
IBD Pharmacogenetics, Royal Devon and Exeter NHS Trust, Exeter, UK
Visschedijk, Marijn C. (författare)
Department of Gastroenterology and Hepatology, University of Groningen, Groningen, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
MacArthur, Daniel G. (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Neale, Benjamin M. (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Ahmad, Tariq (författare)
Peninsula College of Medicine and Dentistry, Exeter, UK
Anderson, Carl A. (författare)
Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Hinxton, UK
Brant, Steven R. (författare)
Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, USA; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA
Duerr, Richard H. (författare)
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh,USA; Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, USA
Silverberg, Mark S. (författare)
Department of Medicine, Inflammatory Bowel Disease Centre, Mount Sinai Hospital, Toronto, Canada
Cho, Judy H. (författare)
Department of Genetics, Yale School of Medicine, New Haven, USA
Palotie, Aarno (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston MA, USA
Saavalainen, Päivi (författare)
Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland
Kontula, Kimmo (författare)
Department of Medicine, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland
Färkkilä, Martti (författare)
Department of Medicine, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland; Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
McGovern, Dermot P. B. (författare)
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA; Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, USA
Franke, Andre (författare)
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
Stefansson, Kari (författare)
deCODE Genetics, Amgen Inc., Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Rioux, John D. (författare)
Research Center, Montreal Heart Institute, Montréal, Canada; Faculté de Médecine, Université de Montréal, Montréal, Canada
Xavier, Ramnik J. (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Daly, Mark J. (författare)
Broad Institute, Massachusetts Institute of Technology, Cambridge MA, USA; Broad Institute, Harvard University, Cambridge MA, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA
Barrett, J. (författare)
IBD Pharmacogenetics, Royal Devon and Exeter NHS Trust, Exeter, UK
de Lane, K. (författare)
IBD Pharmacogenetics, Royal Devon and Exeter NHS Trust, Exeter, UK
Wang, M. H. (författare)
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, USA
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 (creator_code:org_t)
2016-08-09
2016
Engelska.
Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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