Searching for needles in haystacks-the genetics of multiple sclerosis and other common neurological diseases

Recent years have witnessed considerable advances in our understanding of monogenic neurodegenerative diseases, such as hereditary motor sensory neuropathy and Huntington's Chorea. Progress has been slower in the genetic dissection of other more common neurological diseases with a complex mode of inheritance. The identification of relevant genes in some, such as Alzheimer's disease (AD) or Parkinson's disease (PD), has been facilitated by characteristic pathological findings and autosomal dominant inheritance in a proportion of early onset families. Attempts to identify relevant genes for multiple sclerosis have highlighted the role of the major histocompatibility complex, but so far failed to unequivocally implicate other immunologic or structural candidate genes. Six linkage-based whole genome screens have been completed in multiple sclerosis and several regions of interest have been identified. As technology and progress in the human genome project advance, it has become clear that future studies of common neurological diseases will depend critically on the availability of large sample sizes and will have to address issues of disease heterogeneity.