Host Genetic Predisposition to Malaria
The notion of innate genetic differences in susceptibility to malaria was initially proposed by Haldane in his “malaria hypothesis,” which suggested that certain deleterious mutations may be under positive selection because they decrease susceptibility to severe malaria (Haldane 1949). In 1954, A.C. Allison published the first evidence-based study supporting the malaria hypothesis, in which he observed both a lower prevalence of parasitemia and a lower parasite density in Ugandan children with sickle cell trait compared to those with normal red blood cells (Allison 1954). This association suggested that the sickle cell allele, which was fatal when homozygous, was protective against malaria when heterozygous. Further, it provided an evolutionary explanation for why sickle trait was so common in populations where malaria was hyper-endemic. It is now well-established that red blood cell polymorphisms that provide protection against severe malaria have risen to high rates in...
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