Varijabilnost i heritabilnost glikozilacije imunoglobulina G

doctoral thesis

• Title (english): Variability and heritability of immunoglobulin G glycosylation
• Author: Maja Pučić Baković
• Mentor: Gordan Lauc (mentor)
• Committee member: Olga Gornik (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Imunoglobulin G (IgG) je najzastupljeniji glikoprotein u ljudskoj plazmi i glavna efektorska molekula u humoralnom imunološkom odgovoru. Glikani su esencijalne strukturne komponente IgG antitijela pa čak i male promjene u sastavu glikana mogu promjeniti vezanje na Fc receptore i time značajno utjecati na efektorske funkcije IgG-a. Razvoj visoko protočnog pročišćavanja IgG-a iz plazme i optimizacija kromatografske metode visoke razlučivosti i osjetljivosti za analizu IgG glikana omogućili su prvu veliku studiju IgG N-glikoma u populaciji. Rezultati istraživanja na preko 2000 pojedinca otkrili su vrlo veliku varijabilnost dok je heritabilnost IgG glikana bila između 30 i 50%. Fc N-glikozilacija specifična za pojedine potklase IgG-a pokazala je značajnu spolnu i dobnu ovisnost. Najveće promjene u glikozilaciji opažene su kod žena koje prolaze kroz menopauzu. Smjer i intenzitet dobne ovisnosti promjena u glikozilaciji razlikovali su se između djece i odraslih. Cjelogenomskom asocijacijskom studijom IgG N-glikoma identificirano je devet genskih lokusa koji kontroliraju glikozilaciju IgG-a.

Abstract (english)

Immunoglobulin G (IgG) is the most abundant glycoprotein in the human plasma and a major effector molecule of the humoral immune response. Glycans are essential structural components of the IgG antibody and even small changes in glycan composition can have a profound influence on IgG effector function by modulating binding to the Fc receptors. A development of the high-throughput IgG purification from plasma and optimization of chromatographic method for IgG glycan analysis of high resolution and sensitivity enabled a first large-scale study of IgG N-glycome in a population. Results from over 2000 individuals revealed a very high variability while heritability of IgG glycans was generally between 30 and 50%. Subclass-specific IgGFc N-glycosylation analysis showed a significant age and sex-dependance. The most prominent changes in glycosylation in females were observed during menopausal age. Age-dependant changes in children differed from changes in adult population in both,direction and intensity. Genome-wide association study (GWAS) of the IgG N-glycome identified nine genetic loci that control IgG glycosylation.

• Keywords: IgG; N-glikani; HILIC; varijabilnost; heritabilnost; starenje; spol; specifičnost IgG potklasa; cjelogenomska asocijacijska studija
• Keywords (english): IgG; N-glycans; HILIC; variability; heritability; aging; gender; IgG subclass specificity; GWAS
• Language: croatian
• URN:NBN: urn:nbn:hr:217:798397
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-19 11:43:11