title: A genome-wide map of diversity in Plasmodium falciparum.
abstract: 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 mortality. 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 (pi = 1.16 x 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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Volkman
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.forename: David
authors.initials: D
authors.lastname: DeCaprio
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Neafsey
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Danny A
authors.initials: DA
authors.lastname: Milner
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Daily
authors.forename: Ousmane
authors.initials: O
authors.lastname: Sarr
authors.forename: Daouda
authors.initials: D
authors.lastname: Ndiaye
authors.forename: Omar
authors.initials: O
authors.lastname: Ndir
authors.forename: Soulyemane
authors.initials: S
authors.lastname: Mboup
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
authors.forename: Amanda
authors.initials: A
authors.lastname: Lukens
authors.forename: Alan
authors.initials: A
authors.lastname: Derr
authors.forename: Nicole
authors.initials: N
authors.lastname: Stange-Thomann
authors.forename: Skye
authors.initials: S
authors.lastname: Waggoner
authors.forename: Robert
authors.initials: R
authors.lastname: Onofrio
authors.forename: Liuda
authors.initials: L
authors.lastname: Ziaugra
authors.forename: Evan
authors.initials: E
authors.lastname: Mauceli
authors.forename: Sante
authors.initials: S
authors.lastname: Gnerre
authors.forename: David B
authors.initials: DB
authors.lastname: Jaffe
authors.forename: Joanne
authors.initials: J
authors.lastname: Zainoun
authors.forename: Roger C
authors.initials: RC
authors.lastname: Wiegand
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Birren
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hartl
authors.forename: James E
authors.initials: JE
authors.lastname: Galagan
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Dyann F
authors.initials: DF
authors.lastname: Wirth
mesh_terms: D000349:Africa; D000818:Animals; D001208:Asia; D002489:Central America; D002874:Chromosome Mapping / Q000379:methods*; D014644:Genetic Variation; D018503:Genome, Protozoan; D005838:Genotype; D006801:Humans; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013020:South America