Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda.

Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda.
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DOI:
10.1038/s41598-017-11814-9
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发表时间:
2017-09-18
期刊:
影响因子:
4.6
通讯作者:
Day KP
Day KP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ruybal-Pesántez S;Tiedje KE;Tonkin-Hill G;Rask TS;Kamya MR;Greenhouse B;Dorsey G;Duffy MF;Day KP

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恶性疟原虫引起一系列疟疾疾病,从无症状到简单到严重。寄生虫毒力的调查已经与血液阶段的主要表面抗原的不同变体的表达相关联,所述主要表面抗原被称为Pf EMP 1,其由每个基因组多达60个var基因编码。通过观察无并发症疟疾病例中var基因的群体基因组学,我们着手确定是否有任何证据表明,特定var基因或克隆流行结构的选择性扫描与儿童无并发症疾病的发病率有关。通过对乌干达6个哨点var基因的保守DBLα结构域进行测序,我们发现引起儿童单纯性恶性疟原虫病的寄生虫具有高度多样性,每个儿童都有独特的var DBLα库。尽管广泛的变异DBLα多样性和剧目之间的重叠最小,特定的DBLα类型和组在整个乌干达的人口水平上是保守的。无论地理距离或疟疾传播强度如何,这种模式都是相同的。这些数据使我们提出,任何寄生虫都可以引起简单的疟疾疾病,这些不同的寄生虫库由upsA和非upsA var基因组组成。
Plasmodium falciparum causes a spectrum of malarial disease from asymptomatic to uncomplicated through to severe. Investigations of parasite virulence have associated the expression of distinct variants of the major surface antigen of the blood stages known as Pf EMP1 encoded by up to 60 var genes per genome. Looking at the population genomics of var genes in cases of uncomplicated malaria, we set out to determine if there was any evidence of a selective sweep of specific var genes or clonal epidemic structure related to the incidence of uncomplicated disease in children. By sequencing the conserved DBLα domain of var genes from six sentinel sites in Uganda we found that the parasites causing uncomplicated P. falciparum disease in children were highly diverse and that every child had a unique var DBLα repertoire. Despite extensive var DBLα diversity and minimal overlap between repertoires, specific DBLα types and groups were conserved at the population level across Uganda. This pattern was the same regardless of the geographic distance or malaria transmission intensity. These data lead us to propose that any parasite can cause uncomplicated malarial disease and that these diverse parasite repertoires are composed of both upsA and non-upsA var gene groups.
Biopython:用于计算分子生物学和生物信息学的免费 Python 工具。
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