20.500.12556/RUL-147014 Identification of potentially pathogenic variants for autism spectrum disorders using gene-burden analysis Gene-burden analyses have lately become a very successful way for the identification of genes carrying risk variants underlying the analysed disease. This approach is also suitable for complex disorders like autism spectrum disorder (ASD). The gene-burden analysis using Testing Rare Variants with Public Data (TRAPD) software was conducted on whole exome sequencing data of Slovenian patients with ASD to determine potentially novel disease risk variants in known ASD-associated genes as well as in others. To choose the right control group for testing, principal component analysis based on the 1000 Genomes and ASD cohort samples was conducted. The subsequent protein structure and ligand binding analysis using I-TASSER package were performed to detect changes in protein structure and ligand binding to determine a potential pathogenic consequence of observed mutation. The obtained results demonstrate an association of two variants–p.Glu198Lys (PPP2R5D:c.592G>A) and p.Arg253Gln (PPP2R5D:c.758G>A) with the ASD. Substitution p.Glu198Lys (PPP2R5D:c.592G>A) is a variant, previously described as pathogenic in association with ASD combined with intellectual disability, whereas p.Arg253Gln (PPP2R5D:c.758G>A) has not been described as an ASD-associated pathogenic variant yet. The results indicate that the filtering process was suitable and could be used in the future for detection of novel pathogenic variants when analysing groups of ASD patients. medicine genetics genetic tests autism autism spectrum disorder protein structure protein structure prediction Slovenian people computer software polymerase chain reaction pathogenesis mutation medicina genetika genetski testi avtizem true false true Angleški jezik Slovenski jezik Članek v reviji 2023-06-20 13:29:19 2023-06-20 13:29:21 2024-08-27 15:16:05 0000-00-00 00:00:00 2023 0 0 17 str. iss. 5, art. e0273957 Vol. 18 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575:61 1932-6203 10.1371/journal.pone.0273957 152010499 journal.pone.0273957.pdf journal.pone.0273957.pdf 1 3749BE1E14691219E34616E39C7F5265 828f1573e320ab3a54cf86a85fe27feb2de1192aee655ce465278d8676ded3f2 1dc77c2e-0f5f-11ee-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=170359 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0273957 1 55218973-0f5d-11ee-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=170358 Biotehniška fakulteta 0 0 0