Poster Presentation 9th GeneMappers Conference 2012

Gene expression in immune cell subsets – A Risk Gene Study for Multiple Sclerosis (#103)

Judith Field 1 , Grace Foo 2 , Margaret Jordan 3 , Laura J Johnson 1 , Louise Laverick 2 , Melissa Gresle 2 , Jac Charlesworth 4 , Jim Stankovich 5 , Alan Baxter 3 , Helmut Butzkueven 2
  1. Florey Neuroscience Institutes, Parkville, VIC, Australia
  2. Department of Medicine, University of Melbourne, Parkville, Australia
  3. Comparative Genomics Centre, James Cook University, Townsville, Australia
  4. The Menzies Research Institute, Hobart, Australia
  5. The Walter and Eliza Hall Institute, Melbourne, Australia

Genome-wide association scans (GWAS) for multiple sclerosis (MS) have resulted in the identification of multiple genetic loci associated with the risk of developing disease. The challenge now is to ascertain what influence these genetic changes will have on gene expression and/or splicing alterations, and the functional consequences of these changes. In addition, the expression of these genes may be differential in patients with MS compared to healthy controls. Of the SNPs associated with increased risk of MS, three are known to alter both the gene and protein expression of nearby genes. These include SNPs within CD40, , MOG and IL7R. In this study we aim to correlate the known MS risk SNP genotypes with expression levels of nearby genes in immune cell subsets isolated from the peripheral blood of healthy individuals and patients with MS, and to examine any potential differences in gene expression between MS cases and healthy controls. We have successfully isolated pure populations of B cells, CD4 and CD8+ T cells, NK cells and monocytes from peripheral blood followed by RNA extraction and gene expression analysis using the Affymetrix Human 1.0 ST arrays in 21 MS patients and 20 controls. DNA samples from each of the MS patients and controls were used to genotype loci associated with risk of MS. Gene expression analysis using RNA of monocytes has confirmed the genotype-dependent expression of CD40. In addition, we have identified novel expression quantitative trait loci (eQTL) relevant to MS in monocytes and NK cells.