สืบค้นงานวิจัย
Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance
Cerqueira G.C. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance
ผู้แต่ง / หัวหน้าโครงการ (EN): Cerqueira G.C.
บทคัดย่อ (EN): Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced the genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over the period of a rapid increase in the emergence of artemisinin resistance (2001-2014). Results: We evaluate statistical metrics for temporal change in the frequency of individual SNPs, assuming that SNPs associated with resistance increase in frequency over this period. After Kelch13-C580Y, the strongest temporal change is seen at a SNP in phosphatidylinositol 4-kinase, which is involved in a pathway recently implicated in artemisinin resistance. Furthermore, other loci exhibit strong temporal signatures which warrant further investigation for involvement in artemisinin resistance evolution. Through genome-wide association analysis we identify a variant in a kelch domain-containing gene on chromosome 10 that may epistatically modulate artemisinin resistance. Conclusions: This analysis demonstrates the potential of a longitudinal genomic surveillance approach to detect resistance-associated gene loci to improve our mechanistic understanding of how resistance develops. Evidence for additional genomic regions outside of the kelch13 locus associated with artemisinin-resistant parasites may yield new molecular markers for resistance surveillance, which may be useful in efforts to reduce the emergence or spread of artemisinin resistance in African parasite populations. © 2017 The Author(s).
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018383910&doi=10.1186%2fs13059-017-1204-4&partnerID=40&md5=525f1e3b72be748f532e7ac527b441c0
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): gene
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Cerqueira G.C.. "Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance". ไม่ระบุหน่วยงาน. ม.ป.ป.

Cerqueira G.C.. "Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites reveals complex genomic architecture of emerging artemisinin resistance
Cerqueira G.C.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Artemisinin-resistant Plasmodium falciparum malaria Targeting the Cell Stress Response of Plasmodium falciparum to Overcome Artemisinin Resistance Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites Prevalence of Plasmodium falciparum molecular markers of antimalarial drug resistance in a residual malaria focus area in Sabah, Malaysia Combinatorial Genetic Modeling of pfcrt-Mediated Drug Resistance Evolution in Plasmodium falciparum Quantifying connectivity between local Plasmodium falciparum malaria parasite populations using identity by descent IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients Genetic diversity of plasmodium falciparum populations in malaria declining areas of Sabah, East Malaysia Identifying artemisinin resistance from parasite clearance half-life data with a simple Shiny web application Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria
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