Functional genomics and computational analyses in chickens provide powerful tools in order to understand the function and regulation of genes and obtaining new insight into the evolution of gene families in birds and other organisms. Since the sequencing of the genome and the development of high-throughput tools for the exploration of functional elements of the genome, the chicken has reached model organism status. Many of the features of avian biology and organization of the chicken genome make it an ideal model organism for phylogenetics and embryology, along with applications in agriculture and medicine. Although biological pathways of animals do not conform to humans perfectly, many treatment systems and drugs were developed using animal models. Īnimal models have been widely used in order to explore diseases and provide novel insights into the mechanisms of human diseases. The network analysis of the hypoxia-regulated proteins can provide new insight for a better understanding of the molecular mechanisms of the adaptation to anaerobic stress and predict roles of key proteins in human diseases. Therefore, there is no evidence for integrated response to hypoxic stress in humans. It should be noted that numerous investigations have attempted to identify candidate genes and molecular mechanisms involved in the process of adaptation to hypoxia and incidence of disorders however, this process contains complex biological regulatory pathways, leader proteins, and different gene expression patterns. In this way, cerebral anoxia induces the neuron cell death and apoptosis, which will lead to hypoxic brain injury including Alzheimer, Huntington, and Parkinson. Therefore, any alteration or dysfunction in mitochondrial activity can lead to irreparable injuries of the body’s organs, especially in the central nervous system, because the brain is considered as the most sensitive organ to the consumption of oxygen and energy. The lack of normal oxygen level leads to the inadequate mitochondrial metabolism, and also plays a critical role in cell survival. In addition, the low oxygen concentration in high-altitude conditions is another risk factor for diseases. As an example, in high-altitude conditions, high doses of UV (ultraviolet) radiation lead to the DNA damage, cell apoptosis, skin cancer, and tissue injuries in mammals. Many studies aimed to explain the role of hypoxia in diseases and disorders. It has been demonstrated that there is close association between abnormal level of oxygen and human’s disorders and hypoxia is known as the common symptom among human diseases such as cancers, cardiovascular, heart failure, ischemia, cerebral edema, and diabetes. Thus, organisms must adapt to the low oxygen environment to increase the chance of survival. Hypoxia refers to the condition of low oxygen pressure in atmosphere, and is also considered as one of the most important factors that can impact on many biological pathways of cells. Furthermore, we suggested, UV radiation and low oxygen conditions in high-altitude regions may be responsible for the variety of human diseases. 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. 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. Dexamethasone was reported as the candidate toxic drug under the hypoxia condition that implicates diabetes, osteoporosis, and neurotoxicity. Furthermore, calmodulin, and amyloid precursor protein were detected as leader proteins in Alzheimer’s diseases. Lewy body and neuromelanin were reported as key symptoms in Parkinson disease. We found that biological pathways are involved in mitochondrion dysfunctions including peroxynitrous acid production denoted in brain injuries. It was found that hypoxia-associated genes contained several gene networks of disorders such as Parkinson, Alzheimer, cardiomyopathy, drug toxicity, and cancers. The main goal of this study was to visualize the features of diseases due to hypoxia-associated genes by gene network analysis. 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. 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. 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.
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