Approaches to the identification of susceptibility genes

Although previous studies have revealed a great deal about the genetic basis of susceptibility and resistance to parasite infection, there is now an opportunity to considerably enhance understanding through genome-wide association mapping. The application of association mapping to complex inheritance has recently become achievable given reduced costs, sophisticated genotyping platforms and powerful statistical methods which build upon increased knowledge of the linkage disequilibrium structure of the human genome. Linkage mapping and related approaches remain useful for the localization of the rarer genetic variants and candidate region association studies can be a very cost-effective route to progress. However, genome-wide association offers the greatest promise, despite the challenges posed by phenotype complexity, ensuring genotype coverage/quality and robust statistical analysis. The available approaches for mapping genes underlying susceptibility are reviewed here, emphasizing their relative merits and drawbacks and highlighting specific software tools and resources that enable successful mapping.