Genetic approaches to solving common diseases

The pathway to solving simple Mendelian inherited neurological disease is now well established. Barely a month goes by without new linkage data or mutations in a novel gene being reported. These developments are giving insights into a range of neurological conditions from the cortex to the muscle. However, most of these diseases are individually rare, and one of the major challenges facing neuroscience is to devise methods to find the genetic variants that confer risk of common diseases and differential response to treatment. This latter area is an important emerging field known as pharmacogenomics. Unlike Mendelian genetics where effective strategies are well established, the strategies for detecting moderate genetic effects in populations have been problematic. It is likely that a combination of techniques will be used, involving both linkage analysis and linkage disequilibrium mapping. In this review we consider some of the approaches that can be taken to resolve the common genetic variation underlying common disease.