CpG metilacija gena MGAT3 u pacijenata oboljelih od upalnih bolesti crijeva

master's thesis

• Title (english): CpG methylation in MGAT3 gene in patients with inflammatory bowel disease
• Author: Mirna Kassal
• Mentor: Vlatka Zoldoš (mentor)
• Committee member: Vlatka Zoldoš (predsjednik povjerenstva)
• Committee member: Ivana Maguire (član povjerenstva)
• Committee member: Antun Alegro (član povjerenstva)
• Committee member: Anamaria Štambuk (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015-12-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Upalne bolesti crijeva (IBD) su grupa bolesti koje karakterizira kronična upala sluznice probavnog sustava, a najčešće vrste su Crohnova bolest (CD) i ulcerozni kolitis (UC). Ove bolesti povezane su s neravnotežom crijevnog mikrobioma i disfunkcijom imunološkog sustava. Dosadašnja istraživanja provedena na ovim bolestima ukazuju na to da bi imunoglobulin G (IgG) i njegova glikozilacija mogli imati značajnu ulogu u razvoju i progresiji ovih bolesti. Gen MGAT3 kodira za enzim N-acetilglukozaminiltransferazu III koji dodaje N-acetilglukozamin (GlcNAc) na sržnu manozu glikanskih struktura, te na taj način nastaje rasijecajući GlcNAc. Kako rasijecajući GlcNAc nije supstrat za ostale glikoziltransferaze, takva modifikacija rezultira supresijom daljnjeg procesiranja i elongacije N-glikana. Cjelogenomske asocijacijske studije su pokazale povezanost gena MGAT3 s IBD-jem. Cilj ovog istraživanja je analizirati CpG metilaciju u genu MGAT3 iz krvi osoba oboljelih od CD i UC, i usporediti je s metilacijom istog gena u zdravih osoba. U svrhu toga napravljeno je pirosekvenciranje nakon bisulfitne konverzije DNA, te je određen stupanj CpG metilacije u pet fragmenata gena MGAT3. Rezultati pokazaju statistički značajnu promjenu u CpG metilaciji određenih fragmenata gena MGAT3 između pacijenata s IBD-em i zdravih ljudi, što ukazuje na potencijal ovoga gena kao dijagnostičkog biljega za ove bolesti.

Abstract (english)

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. IBD comprises primarily two disorders, which are Crohn's disease (CD) and ulcerative colitis (UC). These diseases are conditions with an imbalnced gut microbiome and the dysfunction of the immune system. Previous research shows that immunoglobulin G (IgG) and its glycosylation might have a role in the development and progression of IBD. MGAT3 gene encodes for the enzyme N-acetylglucosaminyltransferase III that catalyzes the addition of N-acetylglucosamine (GlcNAc) to the mannosyl core of glycans and produces a bisecting GlcNAc. The introduction of the bisecting GlcNAc results in the supression of further processing and elongation of N-glycans, since it can't be a suitable substrate for other glycosyltransferases. Genome-wide association studies (GWAS) have linked the MGAT3 gene with IBD. The aim of this research project is to analize CpG methylation in the MGAT3 gene from blood of people suffering from CD and UC, and to compare it the methylation of healthy people. Pyrosequencing following bisulfite conversion of DNA was done, and the stage of CpG methylation determined in five fragments od the MGAT3 gene. Results show a statistically significant change in CpG methylation in some of the fragments of the MGAT3 gene between patients with IBD and healthy people. This might indicate the potential of this gene of being a biomarker for these diseases.

• Keywords: Crohnova bolest; ulcerozni kolitis; glikozilacija; imunoglobulin G; dijagnostički biljeg
• Keywords (english): Crohns disease; ulcerative colitis; glycosylation; immunoglobulin G; biomarker
• Language: croatian
• URN:NBN: urn:nbn:hr:217:542495
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-04-25 11:48:25