title: Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population.
abstract: We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of beta-thal, beta S, G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous alpha-/alpha-genotype and an overall alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with alpha-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the alpha-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.
authors.affiliation: Department of Biology, University of Rome, Tor Vergata, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Modiano
authors.forename: G
authors.initials: G
authors.lastname: Morpurgo
authors.forename: L
authors.initials: L
authors.lastname: Terrenato
authors.forename: A
authors.initials: A
authors.lastname: Novelletto
authors.forename: A
authors.initials: A
authors.lastname: Di Rienzo
authors.forename: B
authors.initials: B
authors.lastname: Colombo
authors.forename: M
authors.initials: M
authors.lastname: Purpura
authors.forename: M
authors.initials: M
authors.lastname: Mariani
authors.forename: S
authors.initials: S
authors.lastname: Santachiara-Benerecetti
authors.forename: A
authors.initials: A
authors.lastname: Brega
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D004588:Electrophoresis, Cellulose Acetate; D004912:Erythrocytes / Q000469:parasitology; D005819:Genetic Markers; D006579:Heterozygote; D006720:Homozygote; D008288:Malaria / Q000235:genetics / Q000517:prevention & control*; D009390:Nepal; D010641:Phenotype; D010963:Plasmodium falciparum / Q000254:growth & development; D013789:Thalassemia / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D004247:DNA