Gene network analysis to determine the effect of hypoxia-associated genes on brain damages and tumorigenesis using an avian model

Hypoxia refers to the condition of low oxygen pressure in the atmosphere and characterization of response to hypoxia as a biological complex puzzle, is challenging. Previously, we carried out a comparative genomic study by whole genome resequencing of highland and lowland Iranian native chickens to identify genomic variants associated with hypoxia conditions. Based on our previous findings, we used chicken as a model and the identified hypoxia-associated genes were converted to human's orthologs genes to construct the informative gene network. The main goal of this study was to visualize the features of diseases due to hypoxia-associated genes by gene network analysis.

It was found that hypoxia-associated genes contained several gene networks of disorders such as Parkinson, Alzheimer, cardiomyopathy, drug toxicity, and cancers. We found that biological pathways are involved in mitochondrion dysfunctions including peroxynitrous acid production denoted in brain injuries. Lewy body and neuromelanin were reported as key symptoms in Parkinson disease. Furthermore, calmodulin, and amyloid precursor protein were detected as leader proteins in Alzheimer's diseases. Dexamethasone was reported as the candidate toxic drug under the hypoxia condition that implicates diabetes, osteoporosis, and neurotoxicity. Our results suggested DNA damages caused by the high doses of UV radiation in high-altitude conditions, were associated with breast cancer, ovarian cancer, and colorectal cancer.

Our results showed that hypoxia-associated genes were enriched in several gene networks of disorders including Parkinson, Alzheimer, cardiomyopathy, drug toxicity, and different types of cancers. Furthermore, we suggested, UV radiation and low oxygen conditions in high-altitude regions may be responsible for the variety of human diseases.