Chapter 24 : Host Genetic Factors in Resistance and Susceptibility to Malaria

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Well-controlled genetic studies are easier to conduct with mice than with humans, and it has long been known that certain strains of mice consistently show a greater degree of resistance to infection than other strains. It is clear that these differences are primarily genetic, rather than environmental or acquired. This chapter discusses specific genetic loci that have been identified as responsible for some of these differences. Genetic factors also appear to underlie some striking differences in resistance to malaria that have been observed between ethnic groups who live in the same area. The chapter deals with the growing list of genes that show some evidence of influencing resistance to malaria. Glycophorins A and B, encoded by the homologous genes GYPA and GYPB, are major sialoglycoproteins of the erythrocyte membrane, which carries the antigenic determinants for various blood groups. Hemoglobin S (HbS) homozygotes have sickle cell disease, a debilitating and often fatal disorder caused by the red blood cell deformities that result from this structural defect, particularly at low oxygen concentrations. The thalassemias are a group of genetic disorders due to defective production of α- or β- globin chains, arising from a diverse set of deletions and other disruptions of the globin gene clusters on chromosomes 11 and 16. Haptoglobin, encoded by the HP gene, is a protein found in plasma. Parasite sequestration in cerebral capillaries, a hallmark of human cerebral malaria, is notable by its absence in the ANKA (PBA) experimental model.

Citation: Kwiatkowski D, Luoni G. 2005. Host Genetic Factors in Resistance and Susceptibility to Malaria, p 462-479. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch24

Key Concept Ranking

Major Histocompatibility Complex
Tumor Necrosis Factor
Nitric Oxide Synthase
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