A Major Genome Region Underlying Artemisinin Resistance in Malaria

被引：299

作者：

Cheeseman, Ian H. ^{[1
]}

Miller, Becky A. ^{[2
]}

Nair, Shalini ^{[1
]}

Nkhoma, Standwell ^{[1
]}

Tan, Asako ^{[2
]}

Tan, John C. ^{[2
]}

Al Saai, Salma ^{[1
]}

Phyo, Aung Pyae ^{[3
]}

Moo, Carit Ler ^{[3
]}

Lwin, Khin Maung ^{[3
]}

McGready, Rose ^{[3
,4
,5
]}

Ashley, Elizabeth ^{[3
,4
,5
]}

Imwong, Mallika ^{[4
]}

Stepniewska, Kasia ^{[4
,5
,7
]}

Yi, Poravuth ^{[8
]}

Dondorp, Arjen M. ^{[4
,5
]}

Mayxay, Mayfong ^{[6
]}

Newton, Paul N. ^{[5
,6
]}

White, Nicholas J. ^{[4
,5
]}

Nosten, Francois ^{[3
,4
,5
]}

Ferdig, Michael T. ^{[2
]}

Anderson, Timothy J. C. ^{[1
]}

机构：

[1] Texas Biomed Res Inst, San Antonio, TX 78245 USA

[2] Univ Notre Dame, Eck Inst Global Hlth, Dept Biol Sci, Notre Dame, IN 46556 USA

[3] Shoklo Malaria Res Unit, Mae Sot, Tak, Thailand

[4] Mahidol Univ, Fac Trop Med, Bangkok, Thailand

[5] Churchill Hosp, Ctr Trop Med, Oxford OX3 7LJ, England

[6] Mahosot Hosp, Trust Mahosot Hosp, Oxford Trop Med Res Collaborat, Viangchan, Laos

[7] Worldwide Antimalarial Resistance Network, Oxford, England

[8] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia

来源：

SCIENCE | 2012年 / 336卷 / 6077期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

PLASMODIUM-FALCIPARUM; POSITIVE SELECTION; HIGH-ALTITUDE; PARASITES; POPULATIONS; ADAPTATION; EVOLUTION; SPREAD;

D O I：

10.1126/science.1215966

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：79 / 82

页数：4

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