Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection.
BACKGROUND: Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation. METHODS: We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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University of Chicago Press
2014
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| _version_ | 1797079439406792704 |
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| author | Nwakanma, D Duffy, C Amambua-Ngwa, A Oriero, E Bojang, K Pinder, M Drakeley, C Sutherland, C Milligan, P Macinnis, B Kwiatkowski, D Clark, T Greenwood, B Conway, D |
| author_facet | Nwakanma, D Duffy, C Amambua-Ngwa, A Oriero, E Bojang, K Pinder, M Drakeley, C Sutherland, C Milligan, P Macinnis, B Kwiatkowski, D Clark, T Greenwood, B Conway, D |
| author_sort | Nwakanma, D |
| collection | OXFORD |
| description | BACKGROUND: Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation. METHODS: We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium falciparum drug resistance genes in 668 archived parasite-positive blood samples of a Gambian population between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin combination therapy. We separately performed genome-wide sequence analysis of 52 clinical isolates from 2008 to prospect for loci under recent directional selection. RESULTS: Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and mdr1 genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulfadoxine resistance. Temporal changes fit a model incorporating likely selection coefficients over the period. Three of the drug resistance loci were in the top 4 regions under strong selection implicated by the genome-wide analysis. CONCLUSIONS: Genome-wide polymorphism analysis of an endemic population sample robustly identifies loci with detailed documentation of recent selection, demonstrating power to prospectively detect emerging drug resistance genes. |
| first_indexed | 2024-03-07T00:45:52Z |
| format | Journal article |
| id | oxford-uuid:84a29bd2-9d1c-4594-a1ac-6f36e2ee64c1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:45:52Z |
| publishDate | 2014 |
| publisher | University of Chicago Press |
| record_format | dspace |
| spelling | oxford-uuid:84a29bd2-9d1c-4594-a1ac-6f36e2ee64c12022-03-26T21:52:22ZChanges in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:84a29bd2-9d1c-4594-a1ac-6f36e2ee64c1EnglishSymplectic Elements at OxfordUniversity of Chicago Press2014Nwakanma, DDuffy, CAmambua-Ngwa, AOriero, EBojang, KPinder, MDrakeley, CSutherland, CMilligan, PMacinnis, BKwiatkowski, DClark, TGreenwood, BConway, DBACKGROUND: Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation. METHODS: We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium falciparum drug resistance genes in 668 archived parasite-positive blood samples of a Gambian population between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin combination therapy. We separately performed genome-wide sequence analysis of 52 clinical isolates from 2008 to prospect for loci under recent directional selection. RESULTS: Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and mdr1 genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulfadoxine resistance. Temporal changes fit a model incorporating likely selection coefficients over the period. Three of the drug resistance loci were in the top 4 regions under strong selection implicated by the genome-wide analysis. CONCLUSIONS: Genome-wide polymorphism analysis of an endemic population sample robustly identifies loci with detailed documentation of recent selection, demonstrating power to prospectively detect emerging drug resistance genes. |
| spellingShingle | Nwakanma, D Duffy, C Amambua-Ngwa, A Oriero, E Bojang, K Pinder, M Drakeley, C Sutherland, C Milligan, P Macinnis, B Kwiatkowski, D Clark, T Greenwood, B Conway, D Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. |
| title | Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. |
| title_full | Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. |
| title_fullStr | Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. |
| title_full_unstemmed | Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. |
| title_short | Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection. |
| title_sort | changes in malaria parasite drug resistance in an endemic population over a 25 year period with resulting genomic evidence of selection |
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