HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Common variation in the MOG gene influences transcript splicing in humans.

Abstract
Multiple sclerosis (MS) is a complex autoimmune disease characterised by demyelinating lesions in the central nervous system (CNS) and myelin oligodendrocyte glycoprotein (MOG), a CNS-restricted protein expressed on the outer cell membrane of oligodendrocytes, has been linked with disease pathogenesis. We have investigated whether expression of MOG in post-mortem human brain tissue is associated with genetic variations in the MOG gene that have previously been associated with genetic susceptibility to MS (520G>A, rs3130253, V145I and 511G>C, rs2857766, V142L). Using quantitative reverse transcriptase PCR (qPCR), we found that the haplotype containing the 520A (rs3130253A, I145) allele is associated with a 1.7-fold increase in splicing of exon 2 to exon 3, which encodes the extracellular and transmembrane domains of MOG. Using predictive algorithms, we found that the 520G>A variant also alters a putative exonic splicing enhancer (ESE) involving the SC35 and SRp55 RNA-binding proteins, supporting the notion that this variation has a regulatory effect. No consistent differences in allele-specific expression were observed for any of the SNPs using the SNaPshot® method. In this exploratory study we have observed that changes in splicing, but not expression levels, are associated with common genetic variation in the MOG gene. Further work is now required to confirm these data and determine whether this altered MOG expression profile, which is predicted to be over-represented in Northern Europeans with MS, is relevant to the pathophysiology of this debilitating disease.
AuthorsCathy J Jensen, Jim Stankovich, Helmut Butzkueven, Brian J Oldfield, Justin P Rubio
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 229 Issue 1-2 Pg. 225-31 (Dec 15 2010) ISSN: 1872-8421 [Electronic] Netherlands
PMID20800907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier B.V. All rights reserved.
Chemical References
  • MOG protein, human
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
Topics
  • Analysis of Variance
  • Brain (metabolism, pathology)
  • Computational Biology (methods)
  • Gene Frequency
  • Genotype
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Multiple Sclerosis (genetics, pathology)
  • Myelin Proteins
  • Myelin-Associated Glycoprotein (genetics, metabolism)
  • Myelin-Oligodendrocyte Glycoprotein
  • Polymorphism, Single Nucleotide (genetics)
  • Postmortem Changes
  • RNA Splicing (genetics)
  • Statistics, Nonparametric

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: