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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-01-31

AUTHORS

Jianbing Mu, Rachel A. Myers, Hongying Jiang, Shengfa Liu, Stacy Ricklefs, Michael Waisberg, Kesinee Chotivanich, Polrat Wilairata, Srivicha Krudsood, Nicholas J. White, Rachanee Udomsangpetch, Liwang Cui, May Ho, Fengzheng Ou, Haibo Li, Jiangping Song, Guoqiao Li, Xinhua Wang, Suon Seila, Sreng Sokunthea, Duong Socheat, Daniel E. Sturdevant, Stephen F. Porcella, Rick M. Fairhurst, Thomas E. Wellems, Philip Awadalla, Xin-zhuan Su

ABSTRACT

Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome; screening for genes under selection may suggest potential drug or immune targets. 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 approximately 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. More... »

PAGES

268-271

Journal

TITLE

Nature Genetics

ISSUE

3

VOLUME

42

Author Affiliations

  • Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
  • Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27606, USA
  • School of Life Sciences, Xiamen University, Xiamen, Fujian, The People’s Republic of China
  • Genomics Unit, Research Technologies Section, RTB, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
  • Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
  • Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400 Thailand
  • Wellcome-Trust-Mahidol University-Oxford Tropical Medicine Research Programme, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand
  • Pathobiology Department, Faculty of Science, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand
  • Department of Entomology, The Pennsylvania State University, 501 ASI Building, University Park, PA 16802
  • Department of Microbiology and Infectious Disease, University of Calgary, Calgary, Alberta, T2N1N4 Canada
  • Research Center for Qinghao, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
  • Guangzhou University of Chinese Traditional Medicine, Guangzhou, People’s Republic of China
  • National Centre for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
  • Department of Pediatrics, University of Montreal, Faculty of Medicine, Ste. Justine Research Centre, Montreal, Quebec, Canada H3T 1C5
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.528

    DOI

    http://dx.doi.org/10.1038/ng.528

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1052899355

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20101240


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