Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo.
Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo.
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刚果民主共和国VAR2CSA的恶性疟原虫遗传变异。
DOI：
10.1186/s12936-018-2193-9
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发表时间：
2018-01-24
期刊：
影响因子：
3
通讯作者：
Meshnick SR
中科院分区：
文献类型：
--
作者：
Verity R;Hathaway NJ;Waltmann A;Doctor SM;Watson OJ;Patel JC;Mwandagalirwa K;Tshefu AK;Bailey JA;Ghani AC;Juliano JJ;Meshnick SR
刚果民主共和国（DRC）疟疾负担沉重，孕妇的病情会加重。VAR 2CSA蛋白在妊娠相关疟疾（PAM）中起着至关重要的作用，因此量化DRC中var 2csa基因座的多样性对于理解PAM的基本流行病学和开发针对PAM的稳健疫苗是重要的。样本取自刚果民主共和国2013-14年人口与健康调查，重点关注5岁以下儿童。在115个空间簇中对var 2csa基因的一个短亚区进行测序，从而对全国范围内的序列多态性和空间种群结构进行估计。结果表明，var 2csa是高度多态性，并通过平衡选择保持多样性，但是，没有明确的信号，这种多样性的系统发育或地理结构。线性模型表明，一个集群中var 2csa变异的数量与集群患病率直接相关，但与城市化等其他流行病学因素无关。结果表明，刚果民主共和国符合高var 2csa多样性和区域间遗传分化小的全球模式。广泛的多价VAR 2CSA疫苗候选物可以受益于靶向稳定区域和常见变体以解决大量的遗传多样性。本文的在线版本（10.1186/s12936-018-2193-9）包含补充材料，可供授权用户使用。
The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and hence quantifying diversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and in developing a robust vaccine against PAM. Samples were taken from the 2013–14 Demographic and Health Survey conducted in the DRC, focusing on children under 5 years of age. A short subregion of the var2csa gene was sequenced in 115 spatial clusters, giving country-wide estimates of sequence polymorphism and spatial population structure. Results indicate that var2csa is highly polymorphic, and that diversity is being maintained through balancing selection, however, there is no clear signal of phylogenetic or geographic structure to this diversity. Linear modelling demonstrates that the number of var2csa variants in a cluster correlates directly with cluster prevalence, but not with other epidemiological factors such as urbanicity. Results suggest that the DRC fits within the global pattern of high var2csa diversity and little genetic differentiation between regions. A broad multivalent VAR2CSA vaccine candidate could benefit from targeting stable regions and common variants to address the substantial genetic diversity. The online version of this article (10.1186/s12936-018-2193-9) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Tuikue Ndam N;Bischoff E;Proux C;Lavstsen T;Salanti A;Guitard J;Nielsen MA;Coppée JY;Gaye A;Theander T;David PH;Deloron P
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