The Effect of Single Nucleotide Polymorphisms from Genome Wide Association Studies in Multiple Sclerosis on Gene Expression

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 04/2010; 5(4):e10142. DOI: 10.1371/journal.pone.0010142
Source: PubMed


Multiple sclerosis (MS) is a complex neurological disorder. Its aetiology involves both environmental and genetic factors. Recent genome-wide association studies have identified a number of single nucleotide polymorphisms (SNPs) associated with susceptibility to (MS). We investigated whether these genetic variations were associated with alteration in gene expression.
We used a database of mRNA expression and genetic variation derived from immortalised peripheral lymphocytes to investigate polymorphisms associated with MS for correlation with gene expression. Several SNPs were found to be associated with changes in expression: in particular two with HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB4 and HLA-DRB5, one with ZFP57, one with CD58, two with IL7 and FAM164A, and one with FAM119B, TSFM and KUB3. We found minimal cross-over with a recent whole genome expression study in MS patients.
We have shown that many susceptibility loci in MS are associated with changes in gene expression using an unbiased expression database. Several of these findings suggest novel gene candidates underlying the effects of MS-associated genetic variation.

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    • "This would in all probability render the novel transcript susceptible to the nonsense-mediated decay mRNA surveillance pathway [17]. TSFM has been identified as a likely candidate gene in multiple sclerosis susceptibility [18], and its expressio14, para 2n was recently found to be correlated with a variant that alters an enhancer region [19]. Therefore, since overall expression of all TSFM isoforms and of the four reference sequence isoforms (TSFM WT) was not significantly altered by genotype, we conclude that the exon inclusion caused by the SNP is unlikely to be of functional significance. "
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