Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria.
Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity wou...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2674215?pdf=render |
| _version_ | 1818139044135043072 |
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| author | Watcharee Chokejindachai David J Conway |
| author_facet | Watcharee Chokejindachai David J Conway |
| author_sort | Watcharee Chokejindachai |
| collection | DOAJ |
| description | Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity would allow higher levels of linkage disequilibrium (LD) than would exist in more highly endemic areas.Assessment of LD was first made with 11 microsatellite loci widely dispersed in the parasite genome, and 16 microsatellite loci covering a approximately 140 kb region of chromosome 2 (an arbitrarily representative non-telomeric part of the genome), in a sample of 100 P. falciparum isolates. The dispersed loci showed minimal LD (Index of Association, I(S) (A) = 0.013, P = 0.10), while those on chromosome 2 showed significant LD values mostly between loci <5 kb apart. A disease association study was then performed comparing parasites in 113 severe malaria cases and 245 mild malaria controls. Genotyping was performed on almost all polymorphisms in the binding domains of three erythrocyte binding antigens (eba175, eba140 and eba181), and repeat sequence polymorphisms approximately 2 kb apart in each of three reticulocyte binding homologues (Rh1, Rh2a/b, and Rh4). Differences between cases and controls were seen for (i) codons 388-90 in eba175, and (ii) a repeat sequence centred on Rh1 codon 667.Allelic association studies on P. falciparum require dense genotypic markers, even in a population of only moderate endemicity that has more extensive LD than highly endemic populations. Disease-associated polymorphisms in the eba175 and Rh1 genes encode differences in the middle of previously characterised erythrocyte binding domains, marking these for further investigation. |
| first_indexed | 2024-12-11T10:21:50Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T10:21:50Z |
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| spelling | doaj.art-1d700bd2b1ce4265bc01da58ac44d6132022-12-22T01:11:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0145e545410.1371/journal.pone.0005454Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria.Watcharee ChokejindachaiDavid J ConwayStudies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity would allow higher levels of linkage disequilibrium (LD) than would exist in more highly endemic areas.Assessment of LD was first made with 11 microsatellite loci widely dispersed in the parasite genome, and 16 microsatellite loci covering a approximately 140 kb region of chromosome 2 (an arbitrarily representative non-telomeric part of the genome), in a sample of 100 P. falciparum isolates. The dispersed loci showed minimal LD (Index of Association, I(S) (A) = 0.013, P = 0.10), while those on chromosome 2 showed significant LD values mostly between loci <5 kb apart. A disease association study was then performed comparing parasites in 113 severe malaria cases and 245 mild malaria controls. Genotyping was performed on almost all polymorphisms in the binding domains of three erythrocyte binding antigens (eba175, eba140 and eba181), and repeat sequence polymorphisms approximately 2 kb apart in each of three reticulocyte binding homologues (Rh1, Rh2a/b, and Rh4). Differences between cases and controls were seen for (i) codons 388-90 in eba175, and (ii) a repeat sequence centred on Rh1 codon 667.Allelic association studies on P. falciparum require dense genotypic markers, even in a population of only moderate endemicity that has more extensive LD than highly endemic populations. Disease-associated polymorphisms in the eba175 and Rh1 genes encode differences in the middle of previously characterised erythrocyte binding domains, marking these for further investigation.http://europepmc.org/articles/PMC2674215?pdf=render |
| spellingShingle | Watcharee Chokejindachai David J Conway Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria. PLoS ONE |
| title | Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria. |
| title_full | Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria. |
| title_fullStr | Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria. |
| title_full_unstemmed | Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria. |
| title_short | Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria. |
| title_sort | case control approach to identify plasmodium falciparum polymorphisms associated with severe malaria |
| url | http://europepmc.org/articles/PMC2674215?pdf=render |
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