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来自苏丹的杜菲阴性个体中高度保守的间日疟原虫基因组。

Highly conserved Plasmodium vivax genomes in Duffy-negative individuals from Sudan.

作者信息

Schroeder Regan E, Ahmed Safaa, Ford Anthony, Elfaki Mohammed, Hamad Samuel Omer, Ahmed Tarig Mohamed Elfaki, Abukashawa Sumaia Mohamed Ahmed, Manko Emilia, Clark Taane G, Campino Susana, Hamid Muzamil Mahdi Abdel, Lo Eugenia

出版信息

Res Sq. 2025 Aug 7:rs.3.rs-7123704. doi: 10.21203/rs.3.rs-7123704/v1.

Abstract

Duffy-negatives were previously thought to be immune to infections due to Duffy binding protein's (PvDBP1) inability to invade erythrocytes lacking Duffy antigen receptor for chemokines (DARC) expression. Nevertheless, reports of cases are growing throughout Africa and among Duffy-negative people. Although there are alternative invasion mechanisms by , the exact mechanisms in Duffy-negative individuals are unclear. Sudan, with a mixed Duffy-negative and Duffy-positive population, is ideal to study differences between these infections on epidemiological and genetic scales. The goal of this study was to compare Duffy-positive and Duffy-negative infections in Sudanese individuals on epidemiological and genomic scales. We collected epidemiological data and sequenced parasite genomes and found that Duffy-positive individuals had significantly higher parasitemia than Duffy-negatives (p = 0.0000132). Furthermore, Duffy-positive infected genomes were much more diverse than Duffy-negatives, across all 14 chromosomes and 44 specific erythrocyte binding gene candidates. Genes of the merozoite surface protein family account for much of the genetic diversity found. Many erythrocyte binding gene candidates are under selection pressure, both positive and negative. Finally, in genes currently implicated in binding, we have found amino acids that have undergone mutations to a structurally different residue, potentially affecting binding and antigenic conformation.

摘要

由于达菲结合蛋白(PvDBP1)无法侵入缺乏趋化因子达菲抗原受体(DARC)表达的红细胞,此前认为达菲阴性个体对感染具有免疫力。然而,在整个非洲以及达菲阴性人群中,相关病例报告越来越多。尽管存在其他入侵机制,但达菲阴性个体的确切机制尚不清楚。苏丹拥有达菲阴性和达菲阳性混合人群,是在流行病学和基因层面研究这些感染差异的理想之地。本研究的目的是在流行病学和基因组层面比较苏丹个体中达菲阳性和达菲阴性感染情况。我们收集了流行病学数据并对寄生虫基因组进行测序,发现达菲阳性个体的寄生虫血症显著高于达菲阴性个体(p = 0.0000132)。此外,在所有14条染色体和44个特定红细胞结合基因候选基因中,达菲阳性感染的基因组比达菲阴性感染的基因组更加多样化。裂殖子表面蛋白家族的基因在发现的遗传多样性中占很大比例。许多红细胞结合基因候选基因受到正选择和负选择压力。最后,在目前涉及结合的基因中,我们发现一些氨基酸发生了突变,变成了结构不同的残基,这可能会影响结合和抗原构象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/12340914/fcc8f0a1005b/nihpp-rs7123704v1-f0001.jpg

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