Orofacial clefts (OFC) are one of the most common congenital facial malformations. The world incidence is around 1.7 per 1,000 live-born children. OFCs can be divided into syndromic and non-syndromic, which represent up to 70% of all OFCs. Non-syndromic clefts are defined as the clefts that involve the incomplete union of the tissues that form the upper lip, jawbone, and palate and are not associated with any other anomaly outside the anatomical region of the cleft. In addition to an environmental and demographic risk factors, genetic polymorphisms may also increase the risk of developing non-syndromic OFC in offspring. Case - control studies around the world have established a large number of polymorphisms that are thought to be associated with OFC. However, no functional studies, that would mechanistically explain or prove the connection between a particular polymorphism and OFC, have been performed for most of the mentioned polymorphisms. Different bioinformatic tools can be used to assess the pathological potential of an individual polymorphism. The purpose of the master's thesis was to study polymorphisms that were associated with OFC in genetic case - control studies using these tools. 141 polymorphisms were included in the study. First, we used the online tool Ensembl to exclude polymorphisms that are located outside the coding regions and polymorphisms of intron regions that are more than 40 base pairs away from the nearest exon. We identified 10 such single nucleotide polymorphisms (SNP). These polymorphisms are rs7552, rs698, rs9277934, rs357564, rs17563, rs3746101, rs1800471, rs1994798, rs1476413 and rs10498038. We examined the function of the gene in which they are located for all those 10 SNPs in the GeneCards database. An analysis of polymorphisms in the Ensembl database was followed, and finally we evaluated in silico the influence of SNPs on the protein product of the gene and their pathogenic potential using bioinformatic tool Variant Effect Predictor within the Ensembl database. We demonstrated the effect on protein product and pathogenic potential by in silico analysis for the rs9277934 and rs357564 polymorphisms, but no direct association with OFC was found for rs357564. Polymorphisms rs7552, rs9277934, rs17563 and rs3746101 could be associated with OFC based on databases, but as previously mentioned, pathogenic potential was detected only in rs9277934. Although no direct association with OFC was found in rs698, rs1994798, and rs1476413 in the databases, defects in the genes in which these polymorphisms are found, could be associated with other risk factors such as alcohol consumption and homocysteinemia.
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