@article {540101,
	title = {Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum},
	journal = {PLoS Genet},
	volume = {7},
	number = {4},
	year = {2011},
	note = {<p>Van Tyne, DariaPark, Daniel JSchaffner, Stephen FNeafsey, Daniel EAngelino, ElaineCortese, Joseph FBarnes, Kayla GRosen, David MLukens, Amanda KDaniels, Rachel FMilner, Danny A JrJohnson, Charles AShlyakhter, IlyaGrossman, Sharon RBecker, Justin SYamins, DanielKarlsson, Elinor KNdiaye, DaoudaSarr, OusmaneMboup, SouleymaneHappi, ChristianFurlotte, Nicholas AEskin, EleazarKang, Hyun MinHartl, Daniel LBirren, Bruce WWiegand, Roger CLander, Eric SWirth, Dyann FVolkman, Sarah KSabeti, Pardis CengK25 HL080079/HL/NHLBI NIH HHS/T32 AI007638/AI/NIAID NIH HHS/T32 GM007753/GM/NIGMS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.2011/05/03 06:00PLoS Genet. 2011 Apr;7(4):e1001383. doi: 10.1371/journal.pgen.1001383. Epub 2011 Apr 21.</p>},
	month = {Apr},
	pages = {e1001383},
	abstract = {<p>The Plasmodium falciparum parasite{\textquoteright}s ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms ( approximately 1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.</p>},
	keywords = {*Genetic Loci, Antimalarials/*pharmacology, Drug Resistance/*genetics, Ethanolamines/pharmacology, Fluorenes/pharmacology, Gene Dosage, Gene Expression, Genetic Association Studies, Genetic Variation, Genotype, Haplotypes, Linkage Disequilibrium, Malaria, Falciparum/parasitology/prevention \& control, Mefloquine/pharmacology, Phenanthrenes/pharmacology, Plasmodium falciparum/drug effects/*genetics, Polymorphism, Single Nucleotide, Selection, Genetic},
	isbn = {1553-7404 (Electronic)1553-7390 (Linking)},
	author = {Van Tyne, D. and Park, D. J. and Schaffner, S. F. and Neafsey, D. E. and Angelino, E. and Cortese, J. F. and Barnes, K. G. and Rosen, D. M. and Lukens, A. K. and Daniels, R. F. and Milner, D. A., Jr. and Johnson, C. A. and Shlyakhter, I. and Grossman, S. R. and Becker, J.S. and Yamins, D. and Karlsson, E. K. and Ndiaye, D. and Sarr, O. and Mboup, S. and Happi, C. and Furlotte, N. A. and Eskin, E. and Kang, H. M. and Hartl, D. L. and Birren, B. W. and Wiegand, R. C. and Lander, E. S. and Wirth, DF and Volkman, S. K. and Sabeti, P. C.}
}
