Genetska variabilnost v uravnavanju genov serotoninske poti pri bolnikih s shizofrenijo

Hrovatin, Karin (avtor), Kunej, Tanja (mentor), Dolžan, Vita (komentor)

Shizofrenija je kompleksna bolezen z močno negativnimi posledicami za obolele in družbo, zato sta učinkovita diagnostika in zdravljenje posebnega pomena. Vendar pa je zaradi pomanjkanja znanja o molekularnih mehanizmih shizofrenije trenutno nemogoče napovedati odziv na zdravljenje. Za razumevanje molekularnih metabolnih sprememb, ki vodijo do razvoja bolezni, je ključnega pomena razumevanje genetske variabilnosti vključenih genov, ki vodijo do sprememb v metabolnih in signalnih poteh. Vendar pa sta tako serotoninska pot kot njena regulacija in genetika zelo kompleksni. Na področju genetske variabilnosti serotoninske poti pri shizofreniji trenutno ni dobrega pregleda odkritij, ki bi omogočal razumevanje genetske variabilnosti serotoninske poti pri shizofreniji. V tem delu smo 1.) zbrali gene vključene v serotoninsko pot, 2.) opisali njihovo funkcijo v serotoninski poti in 3.) opredelili različne genetske spremembe, ki vplivajo na izražanje in delovanje produktov genov serotoninske poti. Na podlagi tega smo identificirali področja, kjer trenutno primanjkuje raziskav. To bo pripomoglo k boljšemu razumevanju serotoninske poti pri shizofreniji in boljšemu načrtovanju študij na podlagi celotnega reguloma serotoninske poti. Poleg tega smo opredelili tudi nekatere pogoste probleme, ki se pojavljajo pri povezovanju genotipa s fenotipom ter predlagali možne rešitve. To bo omogočilo lažjo interpretacijo sicer kompleksnih rezultatov asociacijskih študij.

• Jezik: Slovenski jezik
• Ključne besede: serotoninska pot, shizofrenija, genetske spremembe, izražanje genov
• Vrsta gradiva: Diplomsko delo/naloga
• Tipologija: 2.11 - Diplomsko delo
• Organizacija: BF - Biotehniška fakulteta
• Založnik: [K. Hrovatin]
• Leto izida: 2018
• PID: 20.500.12556/RUL-101844
• UDK: 606.616.895.8:575.822:577.2(043.2)
• COBISS.SI-ID: 9006713
• Datum objave v RUL: 08.07.2018

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Genetic variability of genes involved in regulation of serotonin pathway in patients with schizophrenia

Izvleček

Schizophrenia is a complex disorder associated with prominent negative consequences for patients and the society. Efficient diagnosis and treatment are thus of utmost importance. However, due to the lack of knowledge about the molecular mechanisms of the disease, it is currently impossible to predict the patients’ treatment response. To elucidate the molecular metabolic changes, which lead to the disease development, it is important to understand the genetic variability of genes leading to changes in metabolic and signal pathways. However, serotonin pathway as well as its regulation and genetics are extremely complex. There is currently no review which would enable the understanding of genetic variability of serotonin pathway in schizophrenia. In this thesis we have 1.) obtained the genes involved in the serotonin pathway, 2.) described their function in the serotonin pathway and 3.) discussed various genetic changes affecting the expression and function of their products. Accordingly, we have identified the topics that are poorly investigated. This will lead to better understanding of the serotonin pathway in schizophrenia and better study design based on the whole serotonin pathway regulome. Additionally, we have identified common problems occurring when associating genotype with phenotype and proposed possible solutions. This will facilitate the interpretation of complex results of association studies.

• Ključne besede: serotonin pathway, schizophrenia, genetic variations, gene expression