How do Multiple Sclerosis Risk Genes Work?
Previously we have collaborated on genome-wide association (GWA) studies to identify genetic variants that increase risk of multiple sclerosis (MS), a severe neurodegenerative autoimmune disease which is more common in Tasmania than in other parts of Australia. So far GWA studies have identified 60 MS risk variants. However little is known about the actions of these
variants. Many variants lie near genes with immunological functions or have been associated with other immune diseases, suggesting that they cause changes in gene expression in immune cells.
To investigate this hypothesis we are collaborating with neurologists, wet-lab geneticists and immunologists at Menzies, at the University of Melbourne and at James Cook University. Our wetlab collaborators are separating five immune cell types from the blood of MS patients and controls and measuring expression levels of all genes in these cells. We have just begun analysing data from two cell types in small numbers of individuals, and have identified seven MS-associated genetic variants that are correlated with expression of nearby genes. Some of these genes are also differentially expressed in cases compared to controls.
There are a number of different statistical and bioinformatics approaches that could be used to explore these data further. For example, by looking at correlation in expression between genes near MS-associated variants, it may be possible to identify common regulatory mechanisms that are important in MS. Joint analyses of expression patterns across multiple cell types may also be revealing. Another valuable information source for understanding MS risk genes is the wealth of public data on gene regulation and transcription factor binding from chromatin-precipitation experiments.
- Dr Jac Charlesworth (Research Fellow)
- Professor Bruce Taylor
- Professor Alan Baxter, James Cook University
- Dr Helmet Butzkueven, University of Melbourne
- Dr Judith Field, University of Melbourne
- Dr Jim Stankovich, University of Melbourne