Abstract

Malaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells. They include the classical polymorphisms that cause sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. More recently however, with improving technology and experimental design, others have been identified that include the Dantu blood group variant, polymorphisms in the red cell membrane protein ATP2B4, and several variants related to the immune response. Characterising how these genes confer their effects could eventually inform novel therapeutic approaches to combat malaria. Nevertheless, all together, only a small proportion of the heritable component of malaria resistance can be explained by the variants described so far, underscoring its complex genetic architecture and the need for continued research.

中文翻译：

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人类遗传学和疟疾耐药性。

摘要

在过去五千年的大部分时间里，疟疾一直是世界许多地区早期死亡的主要原因，因此，它是迄今为止描述的对人类基因组施加选择性压力的最强力量。现在，大约三分之一的严重和复杂疟疾风险的变异性可以通过附加的宿主遗传效应来解释。已鉴定出许多与疟疾保护相关的个体变体，但最重要的都与红细胞的结构或功能有关。它们包括导致镰状细胞性状、α-地中海贫血、G6PD 缺乏症和主要红细胞血型变异的经典多态性。然而，最近，随着技术和实验设计的改进，已经确定了其他包括 Dantu 血型变体，ATP2B4和几个与免疫反应相关的变体。表征这些基因如何赋予其作用最终可以为抗击疟疾的新治疗方法提供信息。然而，总而言之，迄今为止描述的变体只能解释疟疾抗性的可遗传成分的一小部分，强调其复杂的遗传结构和继续研究的必要性。