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Common variation in the MOG gene influences transcript splicing in humans

Citation

Jensen, CJ and Stankovich, J and Butzkueven, H and Oldfield, BJ and Rubio, JP, Common variation in the MOG gene influences transcript splicing in humans, Journal of Neuroimmunology, 229, (1-2) pp. 225-231. ISSN 0165-5728 (2010) [Refereed Article]

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DOI: doi:10.1016/j.jneuroim.2010.07.027

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 (520GNA, rs3130253, V145I and 511GNC, 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 520GNA 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.

Item Details

Item Type:Refereed Article
Keywords:Myelin oligodendrocyte glycoprotein; MOG; Splicing; SNP; Multiple sclerosis; Exonic splicing enhancer
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Neurogenetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Stankovich, J (Dr Jim Stankovich)
ID Code:67283
Year Published:2010
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-03-02
Last Modified:2011-05-03
Downloads:0

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