The Role of Genomics in Studying Genetic Susceptibility to Infectious Disease: Figure 1.

Beta-thalassemia

“…84 -88 Finally, it should be pointed out that there is marked evidence indicating that the high frequency of beta-thalassemia in certain areas of the world is related to heterozygote advantage vis-a-vis Plasmodium falciparum malaria. 89 Exposure to malaria, however, resulted also in the expansion of polymorphisms at many other genetic loci, including human leukocyte antigen (HLA), tumor necrosis factor alpha, and intercellular adhesion molecule-1, which have an important role in the defense mechanisms against infectious diseases. 90 -92 This consideration may indicate that children with beta-thalassemia may respond to infections differently than normal children.…”

Using Mouse Genetics to Understand Infectious Disease Pathogenesis

“…More ominously, there could be a lack of polymorphism in an important host susceptibility gene in either mouse or human because of the differential selective effects of the infectious diseases important in the history of the mouse and human populations. An illustration of the power of infectious disease as a selective force is provided by the high prevalence of apparently deleterious hemoglobin alleles among humans living in regions where malaria infection is extremely common (for review, see Weatherall et al 1997). For these reasons, it is vital to scan for useful genetic polymorphisms in more than one mammalian host, to minimize the chance that a molecule that may be a key target of therapeutic intervention goes undiscovered.…”

Genetic variability in response to infection: malaria and after

“…The growing literature on genetic variation in response to bacteria, viruses, and parasites has been reviewed recently 1,52 and is summarised together with key references in Table 1. It is only possible to outline a few of the principles that are emerging from this field.…”