Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs

被引：142

作者：

Mu, Jianbing ^{[1
]}

Myers, Rachel A. ^{[2
,3
]}

Jiang, Hongying ^{[1
]}

Liu, Shengfa ^{[1
,4
]}

Ricklefs, Stacy ^{[5
]}

Waisberg, Michael ^{[6
]}

Chotivanich, Kesinee ^{[7
]}

Wilairatana, Polrat ^{[7
]}

Krudsood, Srivicha ^{[8
]}

White, Nicholas J. ^{[9
]}

Udomsangpetch, Rachanee ^{[10
]}

Cui, Liwang ^{[11
]}

Ho, May ^{[12
]}

Ou, Fengzhen ^{[13
]}

Li, Haibo ^{[13
]}

Song, Jianping ^{[13
]}

Li, Guoqiao ^{[13
]}

Wang, Xinhua ^{[14
]}

Seila, Suon ^{[15
]}

Sokunthea, Sreng ^{[15
]}

Socheat, Duong ^{[15
]}

Sturdevant, Daniel E. ^{[5
]}

Porcella, Stephen F. ^{[5
]}

Fairhurst, Rick M. ^{[1
]}

Wellems, Thomas E. ^{[1
]}

Awadalla, Philip ^{[2
]}

Su, Xin-zhuan ^{[1
]}

机构：

[1] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA

[2] Univ Montreal, Dept Pediat, Fac Med, St Justine Res Ctr, Montreal, PQ H3C 3J7, Canada

[3] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA

[4] Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China

[5] NIAID, Genom Unit, Res Technol Sect, Res Technol Branch,Rocky Mt Labs,NIH, Hamilton, MT USA

[6] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA

[7] Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok, Thailand

[8] Mahidol Univ, Fac Trop Med, Dept Trop Hyg, Bangkok, Thailand

[9] Mahidol Univ, Wellcome Trust Mahidol Univ Oxford Trop Med Res P, Bangkok, Thailand

[10] Mahidol Univ, Fac Sci, Dept Pathobiol, Bangkok 10400, Thailand

[11] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA

[12] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB, Canada

[13] Res Ctr Qinghao, Guangzhou, Guangdong, Peoples R China

[14] Guangzhou Univ Chinese Med, Guangzhou, Guangdong, Peoples R China

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

来源：

NATURE GENETICS | 2010年 / 42卷 / 03期

基金：

英国惠康基金;

关键词：

POPULATION-STRUCTURE; QUININE RESISTANCE; MALARIA; CHLOROQUINE; MUTATIONS; MEFLOQUINE; THAILAND; PROTEIN;

D O I：

10.1038/ng.528

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome(1,2); screening for genes under selection may suggest potential drug or immune targets(3). Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of high-throughput genotyping methods, inadequate knowledge of parasite population history and time-consuming adaptations of parasites to in vitro culture. Here we report the first Plasmodium GWAS, which included 189 culture-adapted P. falciparum parasites genotyped using a custom-built Affymetrix molecular inversion probe 3K malaria panel array with a coverage of similar to 1 SNP per 7 kb. Population structure, variation in recombination rate and loci under recent positive selection were detected. Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome.

引用

页码：268 / U113

页数：5

共 31 条

[11] Genome-Wide Compensatory Changes Accompany Drug-Selected Mutations in the Plasmodium falciparum crt Gene [J].

Jiang, Hongying ;

Patel, Jigar J. ;

Yi, Ming ;

Mu, Jianbing ;

Ding, Jinhui ;

Stephens, Robert ;

Cooper, Roland A. ;

Ferdig, Michael T. ;

Su, Xin-zhuan .

PLOS ONE, 2008, 3 (06)

[12] Effects of Plasmodium falciparum mixed infections on in vitro antimalarial drug tests and genotyping [J].

Liu, Shengfa ;

Mu, Jianbing ;

Jiang, Hongying ;

Su, Xin-zhuan .

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2008, 79 (02) :178-184

[13] Recombination hotspots and population structure in Plasmodium falciparum [J].

Mu, JB ;

Awadalla, P ;

Duan, JH ;

McGee, KM ;

Joy, DA ;

McVean, GAT ;

Su, XZ .

PLOS BIOLOGY, 2005, 3 (10) :1734-1741

[14] Multiple transporters associated with malaria parasite responses to chloroquine and quinine [J].

Mu, JB ;

Ferdig, MT ;

Feng, XR ;

Joy, DA ;

Duan, JH ;

Furuya, T ;

Subramanian, G ;

Aravind, L ;

Cooper, RA ;

Wootton, JC ;

Xiong, M ;

Su, XZ .

MOLECULAR MICROBIOLOGY, 2003, 49 (04) :977-989

[15] Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome [J].

Mu, Jianbing ;

Awadalla, Philip ;

Duan, Junhui ;

McGee, Kate M. ;

Keebler, Jon ;

Seydel, Karl ;

McVean, Gilean A. T. ;

Su, Xin-zhuan .

NATURE GENETICS, 2007, 39 (01) :126-130

[16] Evidence of Artemisinin-Resistant Malaria in Western Cambodia [J].

Noedl, Harald ;

Se, Youry ;

Schaecher, Kurt ;

Smith, Bryan L. ;

Socheat, Duong ;

Fukuda, Mark M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (24) :2619-2620

[17] Signals of recent positive selection in a worldwide sample of human populations [J].

Pickrell, Joseph K. ;

Coop, Graham ;

Novembre, John ;

Kudaravalli, Sridhar ;

Li, Jun Z. ;

Absher, Devin ;

Srinivasan, Balaji S. ;

Barsh, Gregory S. ;

Myers, Richard M. ;

Feldman, Marcus W. ;

Pritchard, Jonathan K. .

GENOME RESEARCH, 2009, 19 (05) :826-837

[18] Principal components analysis corrects for stratification in genome-wide association studies [J].

Price, Alkes L. ;

Patterson, Nick J. ;

Plenge, Robert M. ;

Weinblatt, Michael E. ;

Shadick, Nancy A. ;

Reich, David .

NATURE GENETICS, 2006, 38 (08) :904-909

[19]

Pritchard JK, 2000, GENETICS, V155, P945

[20] PLINK: A tool set for whole-genome association and population-based linkage analyses [J].

Purcell, Shaun ;

Neale, Benjamin ;

Todd-Brown, Kathe ;

Thomas, Lori ;

Ferreira, Manuel A. R. ;

Bender, David ;

Maller, Julian ;

Sklar, Pamela ;

de Bakker, Paul I. W. ;

Daly, Mark J. ;

Sham, Pak C. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (03) :559-575

← 1 2 3 4 →