Ovalocytosis and cerebral malaria

Genton, Blaise; Al-Yaman, Fadwa; Cs, Mgone; Nast, Alexander; Mm, Paniu; Mp, Alpers; Mokela, D

doi:10.1038/378564a0

Cited by 166 publications

(113 citation statements)

References 8 publications

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“…This deletion results in an abnormal protein structure and function and causes ovalocytosis, an abnormal shape of red blood cells (it is known as Southeast Asian ovalocytosis, or SAO), and mild hemolytic anemia in the heterozygote. The homozygote appears to be lethal because it has never been observed even in progeny from heterozygous matings (Genton et al, 1995).…”

Section: Slc4a1 or Band 3 Ovalocytosismentioning

confidence: 99%

Population genetics of malaria resistance in humans

2011

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Section: Slc4a1 or Band 3 Ovalocytosismentioning

confidence: 99%

Population genetics of malaria resistance in humans

2011

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“…However, studies in PNG have found no evidence for differences in parasite densities among HH, HL and LL genotypes for CR1, although the HL genotype is significantly protected from severe malaria (29). The lack of correlation between protection against severe malaria and reduced parasitemia has been observed for other blood polymorphisms, including α-thalassemia and SAO, and remains a confounding dilemma in the field (30,31). In terms of CR1 polymorphisms, the lack of measurable differences in parasite densities is likely due to the fact that HH, HL, and LL erythrocytes from PNG individuals all have low CR1 levels (<400 molecules per cell) compared with Caucasian individuals.…”

Section: Discussionmentioning

confidence: 99%

Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand

Tham

Wilson

Lopaticki

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

195

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Plasmodium falciparum is responsible for the most severe form of malaria disease in humans, causing more than 1 million deaths each year. As an obligate intracellular parasite, P. falciparum's ability to invade erythrocytes is essential for its survival within the human host. P. falciparum invades erythrocytes using multiple host receptor-parasite ligand interactions known as invasion pathways. Here we show that CR1 is the host erythrocyte receptor for PfRh4, a major P. falciparum ligand essential for sialic acid-independent invasion. PfRh4 and CR1 interact directly, with a K d of 2.9 μM. PfRh4 binding is strongly correlated with the CR1 level on the erythrocyte surface. Parasite invasion via sialic acid-independent pathways is reduced in low-CR1 erythrocytes due to limited availability of this receptor on the surface. Furthermore, soluble CR1 can competitively block binding of PfRh4 to the erythrocyte surface and specifically inhibit sialic acid-independent parasite invasion. These results demonstrate that CR1 is an erythrocyte receptor used by the parasite ligand PfRh4 for P. falciparum invasion.malaria | red blood cell | merozoite | reticulocyte-binding-like homologue

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“…Regardless of its origins, SAO confers extraordinary fitness benefits in areas where P. falciparum is highly endemic. 6 Because of this, it is interesting to consider the extent to which the SAO mutation itself could have facilitated the spread of Austronesian speakers (or their genes) into malarial environments.…”

Section: Discussionmentioning

confidence: 99%

“…1-4 SAO is of interest because there is strong evidence that the condition confers a protective effect with respect to cerebral malaria and malaria-related mortality caused by Plasmodium falciparum. 5,6 This protection most likely is mediated by alteration of the cytoadherence properties of Plasmodium-infected SAO erythrocytes relative to wild-type red blood cells. 7 As such, it is probable that SAO is maintained in malarial populations by natural selection.…”

Section: Introductionmentioning

confidence: 99%

Molecular population genetics of SLC4A1 and Southeast Asian Ovalocytosis

et al. 2009

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Southeast Asian ovalocytosis (SAO) is an erythrocyte abnormality that protects affected individuals from cerebral malaria. This trait is caused by a 27-bp deletion in the SLC4A1 gene, which is lethal when homozygous. We reseqeunced approximately 5 kb of SLC4A1 in an Indonesian population where SAO is prevalent to better understand the evolution of this clinically important trait. The four SAO chromosomes we resequenced share a single haplotype that differs from a sampled non-SAO haplotype only by the 27-bp deletion. Comparison of Indonesian sequence data to that from two other Asian populations (aboriginal Taiwanese and Japanese) shows Indonesian SLC4A1 to be strongly differentiated from the Taiwanese, but not the Japanese. Indeed, the Taiwanese sample contains only chromosomes that are highly divergent from all sampled SAO chromosomes. Because earlier studies have found an association between Austronesian-speakers (who most likely originated in Taiwan) and SAO, our failure to find SAO-like chromosomes in Taiwan is unexpected. Finally, our data find a strong excess of high-frequency derived alleles in all three populations. These alleles include the non-synonymous 'Memphis' variant, which is known to affect anion transport across the erythrocyte membrane. Our data suggest a role for recent natural selection acting on Memphis or a linked variant.

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Ovalocytosis and cerebral malaria

Cited by 166 publications

References 8 publications

Population genetics of malaria resistance in humans

Population genetics of malaria resistance in humans

Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand

Molecular population genetics of SLC4A1 and Southeast Asian Ovalocytosis

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