Publication Date:
2012-04-12
Description:
Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10(-6) to 10(-12)) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355473/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355473/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheeseman, Ian H -- Miller, Becky A -- Nair, Shalini -- Nkhoma, Standwell -- Tan, Asako -- Tan, John C -- Al Saai, Salma -- Phyo, Aung Pyae -- Moo, Carit Ler -- Lwin, Khin Maung -- McGready, Rose -- Ashley, Elizabeth -- Imwong, Mallika -- Stepniewska, Kasia -- Yi, Poravuth -- Dondorp, Arjen M -- Mayxay, Mayfong -- Newton, Paul N -- White, Nicholas J -- Nosten, Francois -- Ferdig, Michael T -- Anderson, Timothy J C -- 089275/Wellcome Trust/United Kingdom -- 093956/Wellcome Trust/United Kingdom -- AI075145/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- R01 AI048071/AI/NIAID NIH HHS/ -- R01 AI075145/AI/NIAID NIH HHS/ -- R37 AI048071/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Apr 6;336(6077):79-82. doi: 10.1126/science.1215966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Texas Biomedical Research Institute, San Antonio, TX 78245, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491853" target="_blank"〉PubMed〈/a〉
Keywords:
Antimalarials/*pharmacology/therapeutic use
;
Artemisinins/*pharmacology/therapeutic use
;
Cambodia
;
DNA Copy Number Variations
;
Drug Resistance/*genetics
;
Gene Frequency
;
Genetic Association Studies
;
*Genome, Protozoan
;
Haplotypes
;
Humans
;
Laos
;
Malaria, Falciparum/drug therapy/*parasitology
;
Microsatellite Repeats
;
Plasmodium falciparum/*drug effects/*genetics
;
Polymorphism, Single Nucleotide
;
Protozoan Proteins/genetics
;
*Selection, Genetic
;
Thailand
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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