Abstract

Although the precise aetiology of multiple sclerosis remains uncertain, available epidemiological data indicates that the disease most likely results from unknown environmental factors acting on genetically susceptible individuals; with “nurture” seeming to account for most of the differences between populations and “nature” primarily determining who is affected within any given population. Results from careful analysis of familial recurrence risks and whole genome linkage studies indicate that susceptibility is determined by a set of relatively common alleles, each exerting only a modest individual effect on risk. Regrettably, identifying these genes has proven to be difficult. The disproportionately large, but still relatively modest effect attributable to the DRB1 gene enabled its early identification, but thereafter three decades of intense international efforts have failed to identify any other loci. Fortunately progress in the human genome project has now reached the point where the resources and technology necessary to identify relevant loci are available and affordable. The first application of these exciting new tools has already confirmed the involvement of Interleukin 7 Receptor (IL7R) and Interleukin 2 Receptor (IL2R). It is clear that the analysis of the complex genetics determining susceptibility to multiple sclerosis is entering a new era