Obesity is a complex metabolic condition in which, in addition to environmental factors, genetic variability also plays an important role. One of the regulatory mechanisms that can influence gene expression and the formation of different transcripts is RNA splicing. In this thesis, we analysed single nucleotide polymorphisms (SNPs) in intronic splice sites in the FLI (fat) and FHI (lean) mouse lines, which were divergently selected for fatness and leanness. The aim of the study was to identify variants in 5’ splice donors and 3’ splice acceptors of introns and to highlight those with the greatest potential impact on RNA splicing. The initial dataset comprised 1,186 unique SNPs in intronic splice regions, distributed across approximately 1,209 genes. The variants were evaluated according to line specificity, their effect on canonical protein-coding transcripts, and their overlap with quantitative trait loci associated with obesity. Annotation-based prioritisation identified five main candidate genes: 2310069G16Rik, Snapc1, Or4f57, Or4f56 and Or4c10b. In addition, 11 transcripts were identified in which SNPs were present at both boundaries of the same intron. The selected variants were also evaluated using the AlphaGenome model, where the strongest interpretable prediction among the main candidates was obtained for variant rs29216035 in the Snapc1 gene. The results provide a set of candidate variants for further functional studies on the role of RNA splicing in metabolic phenotypes.
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