Genetic susceptibility to malaria and other infectious diseases: from the MHC to the whole genome.
There is substantial evidence that host genetic factors play a major role in determining the outcome of infection with many pathogens. Detailed analysis of malaria has identified twelve genes that affect susceptibility in various human populations. However, less attention has been paid to other major infectious diseases where twin studies have identified an important host genetic component to susceptibility. Recent progress in the analysis of the human genome offers exciting prospects for the mapping and identification of new susceptibility and resistance genes for common infectious diseases. Screening of the whole genome in affected sibling pair studies is now feasible by employing highly informative microsatellite markers. In addition, many polymorphic candidate genes have become available for analysis in case-control studies. It is proposed that these new genetic tools offer a powerful approach to the epidemiological analysis of many infectious diseases in humans and supersede traditional genetic approaches to identifying susceptibility genes in mouse models. Progress in characterizing the role of major histocompatibility genes in susceptibility to malaria and other infectious diseases is reviewed before outlining the methodologies for and progress in identifying non-MHC susceptibility genes.
Hill
A V
AV
Wellcome Trust Centre for Human Genetics, Nuffield Department of Clinical Medicine, University of Oxford, U.K.
D000818:Animals; D020022:Genetic Predisposition to Disease; D016678:Genome; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex; D008288:Malaria / Q000235:genetics* / Q000276:immunology*; D012641:Selection, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha