สืบค้นงานวิจัย
Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites
Cheeseman I.H. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites
ผู้แต่ง / หัวหน้าโครงการ (EN): Cheeseman I.H.
บทคัดย่อ (EN): We explored the potential of pooled sequencing to swiftly and economically identify selective sweeps due to emerging artemisinin (ART) resistance in a South-East Asian malaria parasite population. ART resistance is defined by slow parasite clearance from the blood of ART-treated patients and mutations in the kelch gene (chr. 13) have been strongly implicated to play a role. We constructed triplicate pools of 70 slow-clearing (resistant) and 70 fast-clearing (sensitive) infections collected from the Thai-Myanmar border and sequenced these to high (∼150-fold) read depth. Allele frequency estimates from pools showed almost perfect correlation (Lin's concordance = 0.98) with allele frequencies at 93 single nucleotide polymorphisms measured directly from individual infections, giving us confidence in the accuracy of this approach. By mapping genome-wide divergence (FST) between pools of drug-resistant and drug-sensitive parasites, we identified two large (>150 kb) regions (on chrs. 13 and 14) and 17 smaller candidate genome regions. To identify individual genes within these genome regions, we resequenced an additional 38 parasite genomes (16 slow and 22 fast-clearing) and performed rare variant association tests. These confirmed kelch as a major molecular marker for ART resistance (P = 6.03 × 10-6). This two-tier approach is powerful because pooled sequencing rapidly narrows down genome regions of interest, while targeted rare variant association testing within these regions can pinpoint the genetic basis of resistance. We show that our approach is robust to recurrent mutation and the generation of soft selective sweeps, which are predicted to be common in pathogen populations with large effective population sizes, and may confound more traditional gene mapping approaches. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988299737&doi=10.1093%2fmolbev%2fmsu397&partnerID=40&md5=bcf0a8791a1ae7477237827811345354
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Sequence Analysis, DNA
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Cheeseman I.H.. "Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites". ไม่ระบุหน่วยงาน. ม.ป.ป.

Cheeseman I.H.. "Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites
Cheeseman I.H.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance Origin of robustness in generating drug-resistant malaria parasites High-Resolution Single-Cell Sequencing of Malaria Parasites Prevalence of Plasmodium falciparum molecular markers of antimalarial drug resistance in a residual malaria focus area in Sabah, Malaysia Whole-genome sequencing analysis of serially isolated multi-drug and extensively drug resistant Mycobacterium tuberculosis from Thai patients Parasites and asthma Population structure shapes copy number variation in malaria parasites Molecular assays for antimalarial drug resistance surveillance: A target product profile Prevalence of primary HIV drug resistance in Thailand detected by short reverse transcriptase genotypic resistance assay External Quality Assessment Scheme for HIV-1 Drug Resistance Genotyping in Thailand
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