สืบค้นงานวิจัย
A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya
Wendler J.P. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya
ผู้แต่ง / หัวหน้าโครงการ (EN): Wendler J.P.
บทคัดย่อ (EN): Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. Methods and Principal Findings: Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs) and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ) activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ) overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. Conclusions/Significance: Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ. © 2014 Wendler et al.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901490769&doi=10.1371%2fjournal.pone.0096486&partnerID=40&md5=c835c2a732593a7734143e79909b59b9
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): protozoal DNA
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Wendler J.P.. "A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya". ไม่ระบุหน่วยงาน. ม.ป.ป.

Wendler J.P.. "A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya
Wendler J.P.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
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