Onemocnění způsobující mutace versus neutrálnípolymorfizmus: využití bioinformatiky v DNAdiagnostice

Disease CausingMutation versus Neutral Polymorphism: Use of Bioinformatics in DNADiagnostics

Molecular genetic diagnostics is available for increasing number of genetically determined diseases. Awide spectrumof mutations can be detected by laboratory methods. A mutation can be defined as a change in a specific DNAsequence when compared with the reference sequence published in the gene database. However, in some cases it isdifficult to distinguish if the detected sequence variant is a causal mutation or a neutral (polymorphic) variationwithout any effect on phenotype. The interpretation of rare sequence variants of unknown significance detected indisease-causing genes becomes an increasingly important problem. Further analysis on DNA and on protein levelswith the use of bioinformatics are needed to reveal the effect of rare sequence variants. Inherited complex disorders,for example rare hereditary forms of cancer diseases, represent a challenge tomolecular geneticists. The identificationof exact causal mutation directly responsible for the development of the disease and for the assessment of diseaserisk resulting from this genetic variation has further implications. Predictive genetic diagnostics allows identifyrelatives at high risk of genetically determined disease and use of targeted preventive and therapeutic approaches.In severe cases it allows also prenatal or pre-implantation diagnostics.

Key words:
mutation, polymorphism, bioinformatics, predictive program, database.