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Title: Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite
Authors: Naoko Sakihama
Masatsugu Kimura
Kenji Hirayama
Tozo Kanda
Kesara Na-Bangchang
Somchai Jongwutiwes
David Conway
Kazuyuki Tanabe
Osaka Institute of Technology
Osaka City University Medical School
Saitma Medical University Faculty of Medicine
Japanese Association for Mental Health
Mahidol University
Chulalongkorn University
London School of Hygiene & Tropical Medicine
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Apr-1999
Citation: Gene. Vol.230, No.1 (1999), 47-54
Abstract: The C-terminal, cysteine-rich 19 kDa domain of merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a target of the host's humoral immunity and thus a malaria vaccine candidate. Although variation in the 19 kDa domain is limited among parasite isolates, tertiary structure-dependent intramolecular associations between the 19 kDa domain and other parts of MSP- 1 are suggested to be involved in immune evasion by allowing competitive binding of protective and non-protective antibodies directed to their epitopes, which are conformationally in close proximity but separated at the primary structure. Since allelic recombination can account for the major variability of the Msp-1 gene, we examined whether linkage disequilibrium occurs between polymorphic loci in the 5'- and the 3'-region, the latter encoding the 19 kDa domain. From 184 Thai field isolates, we selected 69 isolates with a single allelic type in six variable blocks of Msp-1 as determined by PCR-based allelic typing. All the isolates showed no evidence of recombination in blocks 6 to 16, whereas recombination was apparent in blocks 2 to 6. Sequencing of the 3'-region revealed two potential recombination sites in block 17. Strong linkage disequilibrium was seen between polymorphic loci in the 5'- and 3'-regions. The strength of this disequilibrium did not correlate with distance between loci. We discuss the possible role of epistatic selection on particular association types (haplotypes) of Msp-1.
ISSN: 03781119
Appears in Collections:Scopus 1991-2000

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