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高通量基因分型玻利维亚亚马逊流域间日疟 via 分子反转探针。

High-throughput genotyping of Plasmodium vivax in the Peruvian Amazon via molecular inversion probes.

机构信息

Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA.

Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.

出版信息

Nat Commun. 2024 Nov 25;15(1):10219. doi: 10.1038/s41467-024-54731-y.

DOI:10.1038/s41467-024-54731-y
PMID:39587110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11589703/
Abstract

Plasmodium vivax transmission occurs throughout the tropics and is an emerging threat in areas of Plasmodium falciparum decline, causing relapse infections that complicate treatment and control. Targeted sequencing for P. falciparum has been widely deployed to detect population structure and the geographic spread of antimalarial and diagnostic resistance. However, there are fewer such tools for P. vivax. Leveraging global variation data, we designed four molecular inversion probe (MIP) genotyping panels targeting geographically differentiating SNPs, neutral SNPs, putative antimalarial resistance genes, and vaccine candidate genes. We deployed these MIP panels on 866 infections from the Peruvian Amazon and identified transmission networks with clonality (IBD[identity by descent]>0.99), copy number variation in Pvdbp and multiple Pvrbps, mutations in antimalarial resistance orthologs, and balancing selection in 13 vaccine candidate genes. Our MIP panels are the broadest genotyping panel currently available and are poised for successful deployment in other regions of P. vivax transmission.

摘要

间日疟原虫的传播发生在整个热带地区,并且在恶性疟原虫减少的地区成为一种新出现的威胁,导致复发感染,使治疗和控制变得复杂。针对恶性疟原虫的靶向测序已被广泛用于检测种群结构和抗疟药物及诊断耐药性的地理传播。然而,针对间日疟原虫的这种工具则较少。利用全球变异数据,我们设计了四个分子倒置探针(MIP)基因分型面板,针对具有地理差异的 SNP、中性 SNP、潜在抗疟药物耐药基因和疫苗候选基因。我们在秘鲁亚马逊地区的 866 例感染中部署了这些 MIP 面板,并鉴定出具有克隆性的传播网络(IBD[同源性] > 0.99)、Pvdbp 和多个 Pvrbps 的拷贝数变异、抗疟药物耐药同源物中的突变以及 13 个疫苗候选基因中的平衡选择。我们的 MIP 面板是目前最广泛的基因分型面板,准备在间日疟原虫传播的其他地区成功部署。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/680fa17e6390/41467_2024_54731_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/e3aac5605db0/41467_2024_54731_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/a67dc4ff5519/41467_2024_54731_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/ad550572297c/41467_2024_54731_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/65763755786d/41467_2024_54731_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/680fa17e6390/41467_2024_54731_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/e3aac5605db0/41467_2024_54731_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/a67dc4ff5519/41467_2024_54731_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/ad550572297c/41467_2024_54731_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/65763755786d/41467_2024_54731_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9793/11589703/680fa17e6390/41467_2024_54731_Fig5_HTML.jpg

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