Genes for MS in a cohort of Australian families

Project Outcomes

This project is the continuation of a large, collaborative study investigating the genetics of Multiple Sclerosis (MS) in the Australian population. An initial genome-wide scan of 170 Tasmanian families provided suggestive evidence for MS susceptibility loci in 5 genomic regions. Subsequent detailed mapping of the Human Leukocyte Antigen (HLA) locus also revealed significant association of this genomic region with MS in the Tasmanian cohort. The aim of this next stage of the project was to investigate the genetic regions further in order to refine the loci and characterise any underlying MS susceptibility genes. The five candidate regions were fine mapped using microsatellite markers, and two of the loci, one on chromosome 6q and the other on 10q, remained interesting. In partnership with GlaxoSmithKline, the two loci were genotyped with a dense panel of 852 Single Nucleotide Polymorphisms (SNPs) in a cohort of 62 Tasmanian and 297 Victorian families. At this resolution, only SNPs from the 10q region remained significantly associated with MS susceptibility. The significantly associated SNPs were located at the boundary of the region that was genotyped, so an additional 78 SNPs were added to the analysis. It is with considerable excitement that we can report that a cluster of SNPs on chromosome10q is significantly associated with MS. These SNPs fall within an interesting candidate gene. Further functional analysis is required to confirm and clarify the role this gene plays in susceptibility to MS. The results of this work are currently being prepared for publication.