Mitohondrijski genom pacijenata oboljelih od bolesti COVID-19 u Hrvatskoj

master's thesis

• Title (english): Mitochondrial genome of COVID-19 patients in Croatia
• Author: Antonija Mamić
• Mentor: Marina Korolija (mentor)
• Mentor: Rosa Karlić (sumentor)
• Committee member: Rosa Karlić (predsjednik povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Committee member: Antun Alegro (član povjerenstva)
• Committee member: Kristian Vlahoviček (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-09-30, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

SARS-CoV-2, virus koji uzrokuje bolest COVID-19, je od svoje pojave u ljudskoj populaciji 2019. godine izazvao globalnu pandemiju koja još uvijek traje. Zbog toga je u ovom radu provedeno istraživanje na bolničkim pacijentima oboljelim od bolesti COVID-19. Prikupljeni su podaci za spol, dob, status, simptome i ostale kronične bolesti. Kliničkim podacima je utvrđena veća smrtnost muškaraca, te veća zastupljenost pacijenata starije životne dobi s kritičnim simptomima i kroničnim bolestima. Budući da mitohondrijska DNA svojom individualnom genetičkom uputom direktno oblikuje esencijalne biološke procese kao što su oksidacijska fosforilacija i produkcija reaktivnih kisikovih vrsta, postoji vjerojatnost da individualne razlike u mitohondrijskoj DNA utječu na intenzitet imunosnog odgovora uslijed virusne infekcije. Stoga je naprednim sekvenciranjem mitohondrijskih genoma utvrđen haplotip svakog pacijenta. Distribucija mitohondrijskih makrohaplogrupa i submakrohaplogrupa pacijenata se ne razlikuje značajno od generalne hrvatske populacije. Međutim, otkriven je potencijalni zaštitni učinak makrohaplogrupe K koji treba ispitati na većem uzorku pacijenata, kako bi se dosegla statistička značajnost. Analizom varijanti koje mijenjaju aminokiselinsku sekvencu proteina kod pacijenata nije utvrđena niti jedna promjena direktno povezana s drugim patološkim stanjem. Napokon, ustanovljeno je da za analizu heteroplazmijskih mutacija treba koristiti uzorke krvi na kojima prethodno nisu provođene biokemijske analize.

Abstract (english)

SARS-CoV-2, a COVID-19 causing virus, spread globally in human population from its outbreak in 2019. Therefore, a study was conducted on hospitalized patients with COVID-19. Data for gender, age, status, symptoms, and other chronic diseases were collected. Clinical data have shown a higher mortality of men, and a higher prevalence of elderly patients with critical symptoms and chronic diseases. Because mitochondrial DNA with its individual genetic instruction is directly involved in essential biological processes such as oxidative phosphorylation and the production of reactive oxygen species, it is likely that individual variations in mitochondrial DNA affect the intensity of the immune response due to viral infection. Hence, individual haplotype of each patient was established by advanced mitochondrial genome sequencing. The distribution of mitochondrial macrohaplogroups and submacrohaplogroups of patients does not differ significantly from the general Croatian population. However, a potential protective effect of macrohaplogroup K has been identified, needing to be confirmed on larger patient pool in order to achieve statistical significance. By analyzing variants that cause amino-acid replacement within protein in patients, absence of any documented disease causing variant was established. Finally, it was shown that heteroplasmic mutation study should be performed on intact blood samples, which were not used previously for biochemical analysis.

• Keywords: COVID-19; mtDNA; napredno sekvenciranje DNA; mitohondrijske haplogrupe
• Keywords (english): COVID-19; mtDNA; next generation sequencing; mitochondrial haplogroups
• Language: croatian
• URN:NBN: urn:nbn:hr:217:249128
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-09-30
• Created on: 2021-10-14 12:55:03