Genetic determinants of ammonia-induced acute lung injury in mice.
Kiflai BeinKoustav GangulyTimothy M MartinVincent J ConcelKelly A BrantY P Peter DiSwapna UpadhyayJames P FabisiakLouis J VugaNaftali KaminskiEmrah KostemEleazar EskinDaniel R ProwsAnn-Soo JangGeorge D LeikaufPublished in: American journal of physiology. Lung cellular and molecular physiology (2020)
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 Aatf, Avil, Cep162, Hrh4, Lama3, Plcb4, and 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 pathophysiological roles that could be associated with acute lung injury in several ways.
Keyphrases
- genome wide
- dna methylation
- lipopolysaccharide induced
- high density
- lps induced
- copy number
- high glucose
- diabetic rats
- genome wide association
- room temperature
- anaerobic digestion
- inflammatory response
- gene expression
- poor prognosis
- high resolution
- drug induced
- endothelial cells
- oxidative stress
- type diabetes
- binding protein
- insulin resistance