Schuldt Kathrin, Ehmen Christa, Sievertsen Juergen, Evans Jennifer, May Juergen, Ansong Daniel, Muntau Birgit, Ruge Gerd, Timmann Christian, Agbenyega Tsiri, Horstmann Rolf D, Thye Thorsten
Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
G3 (Bethesda). 2017 Mar 10;7(3):859-864. doi: 10.1534/g3.116.036475.
In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by , the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM) susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or density. Here, we present the first comprehensive analysis of variation in the gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.
在最近的一份报告中，细胞受体CD55被确定为导致最严重形式疟疾的疟原虫入侵人类红细胞所必需的分子。由于这一入侵过程是寄生虫感染期间的关键步骤，因此推测该基因中的遗传变异可能影响严重疟疾（SM）的易感性。我们对人类基因中的罕见和常见遗传变异进行了高分辨率变异发现。基于单变异、联合罕见变异分析和重建单倍型，对来自西非加纳疟疾流行的阿散蒂地区的1700多例SM病例和未受影响的对照个体中的这些变异进行了关联测试。在基因的编码和调控区域共检测到26个遗传变异。其中5个变异以前未知。没有一个单变异、罕见变异或单倍型显示出与SM或疟原虫密度相关的证据。在此，我们首次在SM背景下对基因变异进行了全面分析，并表明加纳研究组中存在的遗传变异似乎不会影响对该疾病的易感性。
