当前位置: X-MOL 学术Hum. Genet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity?
Human Genetics ( IF 3.8 ) Pub Date : 2020-05-27 , DOI: 10.1007/s00439-020-02184-w
Jean-Laurent Casanova 1, 2, 3, 4, 5 , Laurent Abel 1, 3, 4
Affiliation  

Multicellular eukaryotes emerged late in evolution from an ocean of viruses, bacteria, archaea, and unicellular eukaryotes. These macroorganisms are exposed to and infected by a tremendous diversity of microorganisms. Those that are large enough can even be infected by multicellular fungi and parasites. Each interaction is unique, if only because it operates between two unique living organisms, in an infinite diversity of circumstances. This is neatly illustrated by the extraordinarily high level of interindividual clinical variability in human infections, even for a given pathogen, ranging from a total absence of clinical manifestations to death. We discuss here the idea that the determinism of human life-threatening infectious diseases can be governed by single-gene inborn errors of immunity, which are rarely Mendelian and frequently display incomplete penetrance. We briefly review the evidence in support of this notion obtained over the last two decades, referring to a number of focused and thorough reviews published by eminent colleagues in this issue of Human Genetics. It seems that almost any life-threatening infectious disease can be driven by at least one, and, perhaps, a great many diverse monogenic inborn errors, which may nonetheless be immunologically related. While the proportions of monogenic cases remain unknown, a picture in which genetic heterogeneity is combined with physiological homogeneity is emerging from these studies. A preliminary sketch of the human genetic architecture of severe infectious diseases is perhaps in sight.



中文翻译:


危及生命的传染病的人类遗传决定论:遗传异质性和生理同质性?



多细胞真核生物在进化后期从病毒、细菌、古细菌和单细胞真核生物的海洋中出现。这些大型生物暴露于多种多样的微生物并被其感染。那些足够大的甚至可以被多细胞真菌和寄生虫感染。每一次相互作用都是独特的,因为它是在无限多样化的环境中在两个独特的生物体之间进行的。人类感染的个体间临床变异性极高,甚至对于特定的病原体来说,从完全没有临床表现到死亡,就清楚地说明了这一点。我们在这里讨论这样一种观点,即人类危及生命的传染病的决定论可以由单基因先天性免疫错误控制,这种免疫错误很少是孟德尔式的,并且经常表现出不完全外显率。我们简要回顾了过去二十年中获得的支持这一观点的证据,并参考了杰出同事在本期《人类遗传学》中发表的一些重点和全面的评论。似乎几乎所有危及生命的传染病都可能是由至少一种、或许是多种不同的单基因先天性缺陷引起的,尽管如此,这些缺陷可能与免疫学相关。虽然单基因病例的比例仍然未知,但这些研究正在浮现出遗传异质性与生理同质性相结合的景象。严重传染病的人类遗传结构的初步草图也许就在眼前。

更新日期:2020-05-27
down
wechat
bug