Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali.
Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali.
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DOI：
10.3389/fgene.2022.943445
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发表时间：
2022
影响因子：
3.7
通讯作者：
Amambua-Ngwa, Alfred
中科院分区：
文献类型：
--
作者：
Coulibaly, Aoua;Diop, Mouhamadou Fadel;Kone, Aminatou;Dara, Antoine;Ouattara, Amed;Mulder, Nicola;Miotto, Olivo;Diakite, Mahamadou;Djimde, Abdoulaye;Amambua-Ngwa, Alfred
非洲的恶性疟原虫疟疾病例占全球负担的90%以上，马里是11个负担最高的国家之一，占这一年发病率的70%。尽管有大规模的全球干预措施，恶性疟原虫的持续存在是因为其遗传多样性驱动其适应环境变化，对药物产生耐药性并逃避宿主免疫系统的能力。因此，了解人群和干预景观中的恶性疟原虫遗传多样性对于实施消除疟疾的新战略至关重要。这项研究评估了2007年至2017年从7个地点收集的830个马里恶性疟原虫分离株的12，177个高质量SNP的遗传变异。感染的复杂性仍然很高，不同地点之间的差异，并显示出在过去十年中整体复杂性下降的趋势。虽然没有显着的子结构，等位基因频率不同的地理位置，部分驱动采样的时间变化，特别是耐药性和抗原位点。已知耐药标志物（pfcrt、pfdhps、pfdhfr、pfmdr1、pfmdr2和pfk13）的32个突变在人群中的频率至少为2%。在对喹啉类（pfmdr1和pfcrt）和抗叶酸剂（pfdhfr和pfdhps）的抗性的主要标记内和周围的SNP随时间和地理位置而变化，具有强连锁不平衡和基因组中定向选择的特征。这些地理时间的人口也分化的等位基因在免疫相关的基因座，包括蛋白质E140，pfsurfin 8，pfclag8，和pfceltos，以及pftrap，这表明人口之间的单倍型分化的签名。基因组中的几个区域，包括五个已知的耐药位点，显示出差异阳性选择的特征。这些结果表明，药物和免疫压力是马里对恶性疟原虫的主要选择力，但它们对寄生虫基因组的影响在时间和空间上是不同的。随着消灭疟疾战略的实施，需要对与这些基因组变异相互作用的干预措施进行常规评估。
Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented.
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从冈比亚的颞和空间疟原虫对的基因组分析中选择的一致特征。
影响因子：
4.6
作者：
Amambua-Ngwa A;Jeffries D;Amato R;Worwui A;Karim M;Ceesay S;Nyang H;Nwakanma D;Okebe J;Kwiatkowski D;Conway DJ;D'Alessandro U
通讯作者：
D'Alessandro U
影响因子：
5.2
作者：
Gomes PS;Bhardwaj J;Rivera-Correa J;Freire-De-Lima CG;Morrot A
通讯作者：
Morrot A
影响因子：
3
作者：
Konate, Drissa;Diawara, Sory, I;Diakite, Mahamadou
通讯作者：
Diakite, Mahamadou
影响因子：
4.5
作者：
Amambua-Ngwa A;Tetteh KK;Manske M;Gomez-Escobar N;Stewart LB;Deerhake ME;Cheeseman IH;Newbold CI;Holder AA;Knuepfer E;Janha O;Jallow M;Campino S;Macinnis B;Kwiatkowski DP;Conway DJ
通讯作者：
Conway DJ
影响因子：
9.8
作者：
Hemingway J;Shretta R;Wells TN;Bell D;Djimdé AA;Achee N;Qi G
通讯作者：
Qi G