Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Unit of Integrated Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Am J Physiol Lung Cell Mol Physiol. 2021 Jan 1;320(1):L41-L62. doi: 10.1152/ajplung.00276.2020. Epub 2020 Oct 14.
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 prioritized 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 , , , and , which had significant SNP associations, and , , , , , , and , which had suggestive SNP associations. Of these genes, , , , , and are particularly noteworthy and had pathophysiological roles that could be associated with acute lung injury in several ways.
在这项研究中，对一个包含 43 个不同品系的基因多样化的小鼠群体进行了氨暴露实验，并利用单核苷酸多态性 (SNP) 图谱进行了全基因组关联作图。采用转录组分析来帮助解析氨诱导的急性肺损伤的遗传决定因素。根据分子功能、功能域内的非同义 SNP 或改变表达的启动子区域内的 SNP，对编码蛋白进行了优先级排序。这种综合功能方法揭示了 14 个候选基因，包括 、 、 、 和 ，它们具有显著的 SNP 关联，以及 、 、 、 、 、 和 ，它们具有提示性的 SNP 关联。在这些基因中， 、 、 、 、 和 特别值得注意，它们具有与多种方式的急性肺损伤相关的病理生理学作用。
