Many inflammatory bowel disease risk loci include regions that regulate gene expression in immune cells and the intestinal epithelium

Gastroenterology
Michal MokryEdward E S Nieuwenhuis

Abstract

The contribution of genetic factors to the pathogenesis of inflammatory bowel disease (IBD) has been established by twin, targeted-sequencing, and genome-wide association studies. These studies identified many risk loci, and research is underway to identify causal variants. These studies have focused mainly on protein-coding genes. We investigated other functional elements in the human genome, such as regulatory regions. Using acetylated histone 3 lysine 27 chromatin immunoprecipitation and sequencing, we identified tens of thousands of potential regulatory regions that are active in intestinal epithelium (primary intestinal crypts and cultured organoids) isolated from resected material and from biopsies collected during ileo-colonoscopies and immune cells (monocytes, macrophages, CD34(+), CD4(+), and CD8(+)). We correlated these regions with susceptibility loci for IBD. We have generated acetylated histone 3 lysine 27 profiles from primary intestinal epithelium and cultured organoids, which we have made publically available. We found that 45 of 163 single nucleotide polymorphisms (SNPs) associated with IBD overlap specifically with active regulatory elements. In addition, by taking strong linkage disequilibrium into account, a...Continue Reading

References

Dec 19, 2003·Nucleic Acids Research·Albin SandelinBoris Lenhard
Oct 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Michael KrauthammerAndrey Rzhetsky
Apr 20, 2006·Advances in Experimental Medicine and Biology·Edward E S Nieuwenhuis, Richard S Blumberg
Oct 30, 2007·American Journal of Human Genetics·Kai WangMaja Bucan
Nov 1, 2007·Nature Methods·Marieke SimonisWouter de Laat
Feb 28, 2009·Journal of Cellular Biochemistry·Melissa J Fullwood, Yijun Ruan
May 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucia A HindorffTeri A Manolio
Aug 5, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·José BessaJosé Luis Gómez-Skarmeta
Nov 6, 2009·The New England Journal of Medicine·Erik-Oliver GlockerChristoph Klein
Dec 19, 2009·PLoS Genetics·Peter C HollenhorstBarbara J Graves
Feb 16, 2010·Inflammatory Bowel Diseases·Christina M HammSteven R Hunt
Jun 2, 2010·Bioinformatics·Hui JiangWing Hung Wong
Sep 3, 2010·Nature·UNKNOWN International HapMap 3 ConsortiumJean E McEwen
Oct 15, 2010·Nature Biotechnology·Bradley E BernsteinJames A Thomson
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Menno P CreyghtonRudolf Jaenisch
Dec 22, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Elizabeth A WortheyDavid P Dimmock
Mar 29, 2011·Nature·Jason ErnstBradley E Bernstein
May 3, 2011·Gastroenterology·Judy H Cho, Steven R Brant
Oct 21, 2011·The New England Journal of Medicine·Diana C BlaydonDavid P Kelsell
Apr 14, 2012·Science·Batool Akhtar-ZaidiPeter C Scacheri
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Sep 8, 2012·Nature·Amartya SanyalJob Dekker
Sep 8, 2012·Science·Matthew T MauranoJohn A Stamatoyannopoulos
Sep 8, 2012·Genome Research·Marc A SchaubMichael Snyder
Sep 8, 2012·Genome Research·Alan P BoyleMichael Snyder
Oct 5, 2012·The New England Journal of Medicine·Joep de LigtLisenka E L M Vissers
Dec 25, 2012·Nature Genetics·Gosia TrynkaSoumya Raychaudhuri
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng

❮ Previous
Next ❯

Citations

May 17, 2014·Inflammatory Bowel Diseases·Umang JainAndrew W Stadnyk
Sep 27, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Giorgos BamiasFabio Cominelli
Feb 26, 2014·Gastroenterology·Arthur Kaser, Bogdan Pasaniuc
Nov 26, 2015·Biochemical and Biophysical Research Communications·Aping YuanGuanglin Cui
Apr 19, 2016·Best Practice & Research. Clinical Gastroenterology·Jorik M van RijnSabine Middendorp
Aug 11, 2015·Gastroenterology·Dermot McGovernJudy H Cho
Jul 29, 2015·Nature Reviews. Nephrology·Maarten B RookmaakerHans Clevers
Apr 24, 2015·Autophagy·Mohammad SalemOle Haagen Nielsen
May 21, 2015·Genome Medicine·Aashiq H MirzaFlemming Pociot
Jan 17, 2015·Frontiers in Medicine·Mehmet Coskun
May 4, 2016·Current Infectious Disease Reports·Nancy Fu, Titus Wong
May 12, 2016·Annual Review of Immunology·Joanna M PeloquinRamnik J Xavier
Jul 10, 2016·Autoimmunity Reviews·Oded ShamrizOmry Koren
Sep 1, 2016·Mediators of Inflammation·Esmé van der GrachtMitchell Kronenberg
Oct 8, 2016·Frontiers in Pharmacology·Fangkun LiuWei Zhao
Nov 23, 2016·PloS One·Michal MokryEdward E S Nieuwenhuis
Apr 14, 2017·Current Opinion in Gastroenterology·Heitor S P de Souza
Aug 19, 2016·United European Gastroenterology Journal·Chao Li, John F Kuemmerle
Feb 28, 2018·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Magdalena Harakalova, Folkert W Asselbergs
May 23, 2018·Inflammatory Bowel Diseases·Claire Liefferinckx, Denis Franchimont
Jan 6, 2018·Stroke; a Journal of Cerebral Circulation·Melanie D LaarmanYnte M Ruigrok
Aug 24, 2018·The Journal of Clinical Investigation·Ta-Chiang LiuThaddeus S Stappenbeck
Nov 9, 2018·Inflammatory Bowel Diseases·Greeshma Ray, Michelle S Longworth
Nov 16, 2019·International Journal of Molecular Sciences·Claudia BeaurivageDorota Kurek
Aug 18, 2017·JCI Insight·Elizabeth M McDonoughChristopher S Williams
Jan 13, 2015·World Journal of Gastroenterology : WJG·Gian Eugenio TontiniHelmut Neumann
Jun 24, 2016·Journal of Cellular Biochemistry·Mehmet CoskunJesper Thorvald Troelsen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.