Letter abstract
Nature Genetics 39, 113 - 119 (2006)
Published online: 10 December 2006 | doi:10.1038/ng1930
A genome-wide map of diversity in Plasmodium falciparum
Sarah K Volkman1,8, Pardis C Sabeti2,8, David DeCaprio2, Daniel E Neafsey2, Stephen F Schaffner2, Danny A Milner, Jr1, Johanna P Daily1, Ousmane Sarr3, Daouda Ndiaye3, Omar Ndir3, Soulyemane Mboup3, Manoj T Duraisingh1, Amanda Lukens1, Alan Derr2, Nicole Stange-Thomann2, Skye Waggoner2, Robert Onofrio2, Liuda Ziaugra2, Evan Mauceli2, Sante Gnerre2, David B Jaffe2, Joanne Zainoun2, Roger C Wiegand2, Bruce W Birren2, Daniel L Hartl4, James E Galagan2, Eric S Lander2,5,6,7 & Dyann F Wirth1,2
Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality1. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (
= 1.16 
10-3) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite.
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA 02115.
- The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA 02142.
- Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, BP 7325 Dakar, Senegal.
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA 02138.
- Department of Biology, MIT, Cambridge, Massachusetts, USA 02139.
- Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA 02142.
- Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA 02115.
- These authors contributed equally to this work.
Correspondence to: Dyann F Wirth1,2 e-mail: dfwirth@hsph.harvard.edu
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