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.

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使用鸟类模型进行基因网络分析以确定缺氧相关基因对脑损伤和肿瘤发生的影响

缺氧是指大气中氧气压力较低的状况，对缺氧的反应表征作为一个生物复杂难题，具有挑战性。此前，我们通过对高地和低地伊朗本土鸡的全基因组重测序进行了比较基因组研究，以确定与缺氧条件相关的基因组变异。基于我们之前的发现，我们以鸡为模型，将鉴定出的缺氧相关基因转化为人类的直系同源基因，构建信息基因网络。本研究的主要目标是通过基因网络分析来可视化缺氧相关基因引起的疾病的特征。研究发现，缺氧相关基因包含多种疾病的基因网络，如帕金森病、阿尔茨海默病、心肌病、药物毒性和癌症。我们发现生物途径涉及线粒体功能障碍，包括脑损伤中的过氧亚硝酸产生。据报道，路易体和神经黑色素是帕金森病的关键症状。此外，钙调蛋白和淀粉样前体蛋白被检测为阿尔茨海默病的先导蛋白。据报道，地塞米松是缺氧条件下的候选有毒药物，涉及糖尿病、骨质疏松症和神经毒性。我们的研究结果表明，高海拔条件下高剂量紫外线辐射造成的 DNA 损伤与乳腺癌、卵巢癌和结直肠癌有关。我们的结果表明，缺氧相关基因在多种疾病的基因网络中富集，包括帕金森病、阿尔茨海默病、心肌病、药物毒性和不同类型的癌症。此外，我们认为，高海拔地区的紫外线辐射和低氧条件可能是造成多种人类疾病的原因。