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      Comparison of Plasmodium falciparum allelic frequency distribution in different endemic settings by high-resolution genotyping

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          Abstract

          Background

          The diversity of genotyping markers of Plasmodium falciparum depends on transmission intensity. It has been reported that the diversity of the merozoite surface protein 2 ( msp2) is greater in areas of high compared to low endemicity, however, results for msp1 were inconsistent. These previous reports relied on low resolution genotyping techniques.

          Methods

          In the present study, a high-resolution capillary electrophoresis-based technique was applied to genotype samples from areas of different endemicity in Papua New Guinea and Tanzania. For both endemic settings, the diversity of msp1 and msp2 was investigated; the mean multiplicity of infection (MOI) and the F ST values were determined to investigate whether more accurate sizing generates different results.

          Results and Conclusion

          The results of the present study confirmed previous reports of a higher mean MOI for both marker genes and increased genetic diversity in areas of higher endemicity as estimated by the total number of distinct alleles for msp2. For msp1 a minor increase in diversity was observed. Measures of between population variance in allele frequencies (F ST) indicated little genetic differentiation for both marker genes between the two populations from different endemic settings. MOI adjusted for the probability of multiple infections sharing the same allele was estimated by using the msp2 allele frequency distribution and the distribution of observed numbers of concurrent infections. For the high-resolution typing technique applied in this study, this adjustment made little difference to the estimated mean MOI compared to the observed mean MOI.

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          Most cited references28

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          Arlequin (version 3.0): An integrated software package for population genetics data analysis

          Arlequin ver 3.0 is a software package integrating several basic and advanced methods for population genetics data analysis, like the computation of standard genetic diversity indices, the estimation of allele and haplotype frequencies, tests of departure from linkage equilibrium, departure from selective neutrality and demographic equilibrium, estimation or parameters from past population expansions, and thorough analyses of population subdivision under the AMOVA framework. Arlequin 3 introduces a completely new graphical interface written in C++, a more robust semantic analysis of input files, and two new methods: a Bayesian estimation of gametic phase from multi-locus genotypes, and an estimation of the parameters of an instantaneous spatial expansion from DNA sequence polymorphism. Arlequin can handle several data types like DNA sequences, microsatellite data, or standard multi-locus genotypes. A Windows version of the software is freely available on http://cmpg.unibe.ch/software/arlequin3.
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            Estimation of fixation indices and gene diversities.

            Considering the multinomial sampling of genotypes, unbiased estimators of various gene diversity measures in subdivided populations are presented. Using these quantities, formulae for estimating Wright's fixation indices (FIS, FIT, and FST) from a finite sample are developed.
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              Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand.

              Plasmodium falciparum isolates were obtained from Thai patients attending a malaria clinic on the Thai-Kampuchean border over 4 cross-sectional surveys carried out at 3-monthly intervals. The genetic structure of the parasite populations was determined by nested polymerase chain reaction (PCR) amplification of polymorphic regions of 3 P. falciparum antigen genes: msp1, msp2 and glurp. Although a high degree of diversity characterized these isolates, the overall population structure of the parasites associated with patent malaria infections was observed to remain relatively stable over time. The highest degree of polymorphism was observed with msp2, and the mean number of lines per infection (multiplicity of infection) calculated with this marker was higher than that obtained using msp1 or glurp alone, or combined. Infections with > or = 2 parasite lines were seen in 76% of the samples, and were proportionally more numerous at the start and end of the rainy season. Two interesting exceptions to the random distribution were observed and involved 2 allelic variants which in one case were found dissociated (msp1 MAD20-family) and in the other were associated (msp2 FC27-family). The epidemiological significance of these types of data is discussed.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2009
                30 October 2009
                : 8
                : 250
                Affiliations
                [1 ]Swiss Tropical Institute, Socinstr 57, 4002-Basel, Switzerland
                [2 ]Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, Eastern Highland Province 441, Papua New Guinea
                Article
                1475-2875-8-250
                10.1186/1475-2875-8-250
                2774868
                19878560
                6ab10fe6-846f-4dab-b330-22d11c6f07a8
                Copyright © 2009 Schoepflin et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 July 2009
                : 30 October 2009
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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