GENOME-WIDE ASSOCIATION STUDY OF THE HUMAN IMMUNOGLOBULIN G N-GLYCOME

doctoral thesis

• Title (croatian): CJELOGENOMSKA ASOCIJACIJSKA STUDIJA N-GLIKOMA LJUDSKOG IMUNOGLOBULINA G
• Author: Azra Frkatović
• Mentor: Gordan Lauc (mentor)
• Mentor: Frano Vučković (komentor)
• Committee member: Olga Gornik Kljaić (predsjednik povjerenstva)
• Committee member: Kristian Vlahoviček (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-07-05, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Glycosylation of the immunoglobulin G (IgG) is a complex biosynthetic process that affects
protein stability and effector functions. Genome-wide association study of IgG N-glycan traits
in seven cohorts of European descent was conducted to discover genomic regions associated
with IgG glycosylation. The tested phenotypes were defined as the percentage of presence of
individual sugar units in the total IgG glycome. Discovery meta-analysis resulted in 42
genome-wide significant loci, 13 of which were novel. Prioritization of the genes mapped in
the associated regions resulted in 83 candidate genes which are enriched in cellular transport,
B and T cell development and immune system, suggesting that not only the regulation of
glycoenzyme gene expression but intracellular transport and clonal selection and proliferation
shape the IgG glycopatterns. The findings provide the basis for functional studies to confirm
the role of prioritized genes in IgG N-glycosylation.

Abstract (croatian)

Glikozilacija imunoglobulina G (IgG) je kompleksna postranslacijska modifikacija koje utječe
na stabilnost proteina i njegove efektorske funkcije. Provedena je cjelogenomska asocijacijska
studija N-glikanskih svojstava ljudskog IgG-a u sedam skupina ispitanika europskog podrijetla
s ciljem otkrivanja novih genomskih regija povezanih s glikozilacijom IgG-a. Testirani
fenotipovi definirani su kao postotak prisutnosti dane jedinice šećera u ukupnom IgG glikomu.
Početna meta-analiza identificirala je 42 statistički značajna lokusa, od kojih je 13
novotokrivenih. Prioritiziranje gena mapiranih u otkrivenim regijama rezultiralo je s 83 gena
koja su obogaćena u skupovima vezanim za stanični transport, razvoj B i T stanica te
imunološki sustav, što sugerira da pored regulacije ekspresije gena za glikoenzime,
unutarstanični transport i klonska selekcija i proliferacija oblikuju glikoprofil ljudskog IgG-a.
Rezultati ove studije predstavljaju osnovu za funkcionalne studije kako bi se potvrdila uloga
prioritiziranih gena u N-glikozilaciji.

• Keywords: Genome-wide association study; immunoglobulin G; N-glycosylation; immune system; pleiotropy
• Keywords (croatian): Cjelogenomska asocijacijska studija; imunoglobulin G; N-glikozilacija; imunološki sustav; pleiotropija
• Language: english
• URN:NBN: urn:nbn:hr:217:648759
• Promotion: 2022
• 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: Embargoed access; Embargo expiration date: 2024-07-05
• Created on: 2022-11-22 13:50:46