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  • 标题:Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice
  • 本地全文:下载
  • 作者:Katelyn Vendrely Brenneman ; Xue Li ; Sudhir Kumar
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:4
  • 页码:1-19
  • DOI:10.1016/j.isci.2022.104095
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryClassical malaria parasite genetic crosses involve isolation, genotyping, and phenotyping of progeny parasites, which is time consuming and laborious. We tested a rapid alternative approach—bulk segregant analysis (BSA)—that utilizes sequencing of bulk progeny populations with and without drug selection for rapid identification of drug resistance loci. We used dihydroartemisinin (DHA) selection in two genetic crosses and investigated how synchronization, cryopreservation, and the drug selection regimen impacted BSA success. We detected a robust quantitative trait locus (QTL) atkelch13in both crosses but did not detect QTLs at four other candidate loci. QTLs were detected using synchronized, but not unsynchronized progeny pools, consistent with the stage-specific action of DHA. We also successfully applied BSA to cryopreserved progeny pools, expanding the utility of this approach. We conclude that BSA provides a powerful approach for investigating the genetic architecture of drug resistance inPlasmodium falciparum.Graphical abstractDisplay OmittedHighlights•Bulk segregant analysis (BSA) rapidly maps drug resistance loci inP. falciparum•BSA with dihydroartemisinin identifieskelch13, providing proof-of-principle•Synchronization of the bulk population is necessary when using stage-specific drugs•Cryopreserved progeny pools can be used for BSABiological sciences; Genomics; Parasitology
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