The elevated rate of fat accumulation in obese individuals has a multifactorial etiology. In extremely rare cases, it can develop as a result of a single mutation with large effect (monogenic form), or as a combined effect of a multitude of less impactful genetic variants representing a polygenic form of obesity. This form is harder to diagnose since the effect size of different genes is very small and the type of action is still largely unknown. HIF gene family is an example of metabolically relevant genes, which are also active in the fat tissue of obese individuals. They have been linked with chronic inflammation, which is one of the causes ort he development of type 2 diabetes and other metabolic diseases. Their possible role in the onset of polygenic obesity has not yet been recognized. The goal of this study was to find differences in regulatory regions of the Hif gene family (Hif1, Epas1 in Hif3a) between two groups of selectively breed laboratory mice. After 60 generations of selection there is more than a five-fold difference in body fat percentage between them. All discovered variations were positioned in the reference sequence from the Ensembl and SwissRegulon databases, and visualized in the GenomeBrowse program. Results showed that there are 418 sequence differences between the lines, most of which are located in the Hif1a gene of the fat line. Out of all detected variants, 24 of them are located within regulatory regions. We have selected 28 of the most promising sequence variants based on their location and GERP value, that represent viable candidates for future studies aimed at identifying their causal role in the obesity development.
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