| 2009 |
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| Population diversity and antibody selective pressure to Plasmodium falciparum MSP1
block2 locus in an African malaria-endemic setting. |
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| Noranate, N., Prugnolle, F., Jouin, H., Tall, A., Marrama, L., Sokhna, C., Ekala, M. T., Guillotte,
M., Bischoff, E., Bouchier, C., Patarapotikul, J., Ohashi, J., Trape, J. F., Rogier, C., and Mercereau-Puijalon, O. |
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| Institut Pasteur, Unite d'Immunologie Moleculaire des Parasites, CNRS URA 2581, 28 rue du Dr
ROUX, 75724 Paris Cedex 15, France noranate@gmailcom |
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| Abstract: BACKGROUND: Genetic evidence for diversifying selection identified the Merozoite
Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family
types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and
arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection
operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population
allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission
is intense and perennial. RESULTS: Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR
fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite
population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population
diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic
sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was
moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences
shared by numerous allelic forms within a family type. Seroreactivity to K1-, M |
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| Published in:BMC.Microbiol. 9, 219. 2009. |
