Advertisement
Research Article

Analysis of Germline GLI1 Variation Implicates Hedgehog Signalling in the Regulation of Intestinal Inflammatory Pathways

  • Charlie W Lees equal contributor mail,

    equal contributor Contributed equally to this work with: Charlie W Lees, William J Zacharias

    To whom correspondence should be addressed. E-mail: Charlie.lees@ed.ac.uk (CWL); dgumucio@umich.edu (DLG)

    Affiliations: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom, Immunobiology Group, Medical Research Council (MRC) Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

    X
  • William J Zacharias equal contributor,

    equal contributor Contributed equally to this work with: Charlie W Lees, William J Zacharias

    Affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

    X
  • Mark Tremelling,

    Affiliation: Inflammatory Bowel Disease (IBD) Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom

    X
  • Colin L Noble,

    Affiliation: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom

    X
  • Elaine R Nimmo,

    Affiliation: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom

    X
  • Albert Tenesa,

    Affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom

    X
  • Jennine Cornelius,

    Affiliation: Department of Pathology, Genentech, Inc, South San Francisco, California, United States of America

    X
  • Leif Torkvist,

    Affiliation: Department of Medical & Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden

    X
  • John Kao,

    Affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

    X
  • Susan Farrington,

    Affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom

    X
  • Hazel E Drummond,

    Affiliation: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom

    X
  • Gwo-Tzer Ho,

    Affiliation: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom

    X
  • Ian D. R Arnott,

    Affiliation: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom

    X
  • Henry D Appelman,

    Affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

    X
  • Lauri Diehl,

    Affiliation: Department of Pathology, Genentech, Inc, South San Francisco, California, United States of America

    X
  • Harry Campbell,

    Affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom

    X
  • Malcolm G Dunlop,

    Affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom

    X
  • Miles Parkes,

    Affiliation: Inflammatory Bowel Disease (IBD) Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom

    X
  • Sarah E. M Howie,

    Affiliation: Immunobiology Group, Medical Research Council (MRC) Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

    X
  • Deborah L Gumucio mail,

    To whom correspondence should be addressed. E-mail: Charlie.lees@ed.ac.uk (CWL); dgumucio@umich.edu (DLG)

    Affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

    These authors are joint senior authors on this work.

    X
  • Jack Satsangi

    Affiliation: Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom

    These authors are joint senior authors on this work.

    X
  • Published: December 09, 2008
  • DOI: 10.1371/journal.pmed.0050239

About the Authors

Charlie W Lees, Colin L Noble, Elaine R Nimmo, Hazel E Drummond, Gwo-Tzer Ho, Ian D. R Arnott, Jack Satsangi
Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, United Kingdom
Charlie W Lees, Sarah E. M Howie
Immunobiology Group, Medical Research Council (MRC) Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
William J Zacharias, Deborah L Gumucio
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
Mark Tremelling, Miles Parkes
Inflammatory Bowel Disease (IBD) Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Albert Tenesa, Susan Farrington, Harry Campbell, Malcolm G Dunlop
Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom
Jennine Cornelius, Lauri Diehl
Department of Pathology, Genentech, Inc, South San Francisco, California, United States of America
Leif Torkvist
Department of Medical & Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden
John Kao
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
Henry D Appelman
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

Corresponding Authors

Competing Interests

Lauri Diehl is a paid employee of Genentech, Inc and a stockholder in that company. While this paper does not describe any Genentech product, it is possible that these findings may be relevant to a pathway or pathways of interest to the company for current or future therapeutic agents. None of the other authors have any competing interests to declare.

Author Contributions

CWL, WJZ, CLN, ERN, LD, DLG, and JS designed the experiments/the study. CWL, WJZ, MT, CLN, JC, LT, JK, HED, IDRA, HDA, LD, MP, and SEMH collected data or did experiments for the study. CWL, WJZ, MT, AT, JK, LD, and DLG analyzed the data. CWL, MT, CLN, LT, G-TH, IRDA, SF, MGD and MP enrolled patients. CWL and WJZ wrote the first draft of the paper. CWL, WJZ, MT, AT, HC, MGD, SEMH, DLG, and JS contributed to writing the paper.