title: Progress in deciphering the genetics of multiple sclerosis.
abstract: OBJECTIVE
  Multiple sclerosis is the most common neurological disease affecting young adults. The aetiology is unknown, although many clues point to an autoimmune inflammatory nature. Family studies of multiple sclerosis have shown familial aggregation, and therefore suggest that the disease entails a genetic component that has been widely studied. Some of the studies from the extensive literature in the field of multiple sclerosis genetics published in the past year are discussed here.
  
  
  RESULTS
  A number of the recent publications considered in this review have reconfirmed the well-known association with the major histocompatibility complex as well as identifying that there are at least two important loci within this region. These findings add further complexity to the role of the major histocompatibility complex in multiple sclerosis. Links to other diseases have been few for multiple sclerosis, but the association with diabetes in the Sardinian population and, perhaps, a 'protective' effect of Down's syndrome can now be added. Numerous candidate genes for susceptibility and disease-modifying effect have also been studied in the literature, but with few replications. Associations with components of the endocrine and the neuro-endocrine system have also been considered in this review along with the potential value of microarray analysis.
  
  
  CONCLUSIONS
  Multiple sclerosis is a complex trait that is associated with the major histocompatibility complex, although the form of this association may not be as straightforward as previously thought. Recent findings raise the possibility of an association with haplotype blocks rather than with single alleles. The finding of allelic heterogeneity within the major histocompatibility complex, as with the Sardinians, adds an additional layer of complexity. Genome scans for this and other autoimmune diseases have often been notably disappointing despite many claims for linkages. The reasons for the difficulty may encompass locus heterogeneity, small effects and phenocopies, among others. A variety of attempts to study more restricted populations are in progress, including rare individual pedigrees with high recurrence risk.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, UK.
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Herrera
authors.forename: George C
authors.initials: GC
authors.lastname: Ebers
mesh_terms: D003920:Diabetes Mellitus / Q000235:genetics; D018450:Disease Progression; D004314:Down Syndrome / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D011960:Receptors, Estrogen / Q000235:genetics
chemical_list: D006681:HLA-D Antigens; D011960:Receptors, Estrogen