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Genetic Determinants of Ammonia-Induced Acute Lung Injury in Mice
American Journal of Physiology-Lung Cellular and Molecular Physiology ( IF 4.9 ) Pub Date : 2020-10-14 , DOI: 10.1152/ajplung.00276.2020
Kiflai Bein 1 , Koustav Ganguly 1, 2 , Timothy M Martin 1 , Vincent J Concel 1 , Kelly A Brant 1 , Y P Peter Di 1 , Swapna Upadhyay 1, 2 , James P Fabisiak 1 , Louis J Vuga 3, 4 , Naftali Kaminski 3, 4, 5 , Emrah Kostem 6 , Eleazar Eskin 6 , Daniel R Prows 7 , Ann-Soo Jang 8 , George D Leikauf 1
Affiliation  

In this study, a genetically diverse panel of 43 mouse strains was exposed to ammonia and genome-wide association mapping was performed employing a single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was used to help resolve the genetic determinants of ammonia-induced acute lung injury. The encoded proteins were prioritize based on molecular function, nonsynonymous SNP within a functional domain, or SNP within the promoter region that altered expression. This integrative functional approach revealed 14 candidate genes that included Aatf, Avil, Cep162, Hrh4, Lama3, Plcb4, Ube2cbp, which had significant SNP associations, and Aff1, Bcar3, Cntn4, Kcnq5, Prdm10, Ptcd3, and Snx19, which had suggestive SNP associations. Of these genes, Bcar3, Cep162, Hrh4, Kcnq5, and Lama3 are particularly noteworthy and had pathophysiologic roles that could be associated with acute lung injury in several ways.

中文翻译:

氨气所致小鼠急性肺损伤的遗传决定因素

在这项研究中,将 43 种小鼠品系的遗传多样性面板暴露于氨气中,并使用单核苷酸多态性 (SNP) 组装进行全基因组关联作图。转录组学分析用于帮助解决氨诱导的急性肺损伤的遗传决定因素。编码的蛋白质根据分子功能、功能域内的非同义 SNP 或启动子区域内改变表达的 SNP 进行优先排序。这种综合功能方法揭示了 14 个候选基因,包括 Aatf、Avil、Cep162、Hrh4、Lama3、Plcb4、Ube2cbp,它们具有显着的 SNP 关联,以及 Aff1、Bcar3、Cntn4、Kcnq5、Prdm10、Ptcd3 和 Snx19,它们具有暗示性的 SNP协会。在这些基因中,Bcar3、Cep162、Hrh4、Kcnq5、
更新日期:2020-10-15
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