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麻风病作为常见传染病易感性的遗传模型。

Leprosy as a genetic model for susceptibility to common infectious diseases.

作者信息

Alter Andrea, Alcaïs Alexandre, Abel Laurent, Schurr Erwin

机构信息

McGill Centre for the Study of Host Resistance, The Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, H3G 1A4, QC, Canada.

出版信息

Hum Genet. 2008 Apr;123(3):227-35. doi: 10.1007/s00439-008-0474-z. Epub 2008 Feb 5.

Abstract

Leprosy (Hansen's disease) is a human infectious disease that can be effectively treated with long-term administration of multi-drug therapy. In 2006, over 250,000 new cases were reported to the World Health Organization. In the nineteenth century, disagreement among leprologists regarding the hereditary or infectious nature of leprosy was resolved with the identification of the etiological agent, Mycobacterium leprae. However, epidemiological studies maintain the importance of host genetics in leprosy susceptibility. A model free genome-wide linkage scan in multi-case families from Vietnam led to the positional cloning of global genetic risk factors in the PARK2/PACRG and LTA genes. The process of identifying the susceptibility variants provided invaluable insight into the replication of genetic effects, particularly the importance of considering population-specific linkage-disequilibrium structure. As such, these studies serve to improve our understanding of leprosy pathogenesis by implicating novel biological pathways while simultaneously providing a genetic model for common infectious diseases.

摘要

麻风病(汉森氏病)是一种人类传染病,通过长期使用多药疗法可得到有效治疗。2006年,向世界卫生组织报告的新病例超过25万例。在19世纪,随着麻风病病原体麻风分枝杆菌的发现,麻风病学家们关于麻风病遗传性或传染性本质的分歧得以解决。然而,流行病学研究证实宿主遗传学在麻风病易感性方面具有重要作用。在来自越南的多个病例家庭中进行的一项无模型全基因组连锁扫描,导致在PARK2/PACRG和LTA基因中定位克隆出全球遗传风险因素。识别易感性变异的过程为遗传效应的复制提供了宝贵的见解,特别是考虑群体特异性连锁不平衡结构的重要性。因此,这些研究通过涉及新的生物学途径,在增进我们对麻风病发病机制理解的同时,也为常见传染病提供了一个遗传模型。

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