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镰刀型血红蛋白对疟疾的保护作用取决于寄生虫的基因型
2021-12-12 22:32

英国牛津大学Dominic P. Kwiatkowski等研究人员合作发现,镰刀型血红蛋白对疟疾的保护作用取决于寄生虫的基因型。该项研究成果于2021年12月9日在线发表在《自然》杂志上。

研究人员在3346名冈比亚和肯尼亚儿童中寻找了候选宿主和寄生虫基因变异之间的联系,这些儿童被确认患有恶性疟原虫引起的严重疟疾。研究人员发现宿主的镰状血红蛋白(HbS)和寄生虫基因组的三个区域之间有很强的关联性,这不是人口结构或其他协变量所能解释的,并在其他样本中得到了重复。与HbS相关的等位基因包括2号染色体上的酰基-CoA合成酶家族成员PfACS8的非同义变体,2号染色体的第二个区域,以及11号染色体上含有结构变异的区域。这些等位基因具有很强的连锁不平衡性,其频率与不同人群的HbS频率相吻合,特别是在非洲比世界其他地区更常见。

通过比较病例和人群对照,估计HbS对严重疟疾的保护作用因这三个基因座上的寄生虫基因型不同而有很大差异。这些发现为探究寄生虫基因组中与HbS相关多态性的生物学和流行病学意义,以及导致其在非洲恶性疟原虫种群中的高频率和强连锁不平衡的进化力量开辟了一条新途径。

据悉,宿主的遗传因素可以赋予对疟疾的抵抗力,这提出了一个问题,即这是否导致了寄生虫种群的进化适应。

附:英文原文

Title: Malaria protection due to sickle haemoglobin depends on parasite genotype

Author: Band, Gavin, Leffler, Ellen M., Jallow, Muminatou, Sisay-Joof, Fatoumatta, Ndila, Carolyne M., Macharia, Alexander W., Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Nguyen, Thuy, Gonalves, Snia, Ariani, Cristina V., Stalker, Jim, Pearson, Richard D., Amato, Roberto, Drury, Eleanor, Sirugo, Giorgio, dAlessandro, Umberto, Bojang, Kalifa A., Marsh, Kevin, Peshu, Norbert, Saelens, Joseph W., Diakit, Mahamadou, Taylor, Steve M., Conway, David J., Williams, Thomas N., Rockett, Kirk A., Kwiatkowski, Dominic P.

Issue&Volume: 2021-12-09

Abstract: Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. In this study we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children ascertained with severe malaria due to Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, that is not explained by population structure or other covariates, and that is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the acyl-CoA synthetase family member2–4 PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium, and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome, and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.

DOI: 10.1038/s41586-021-04288-3

Source: https://www.nature.com/articles/s41586-021-04288-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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