Molekularna i paleopatološka analiza potencijalnih slučajeva reumatoidnog artritisa u ljudi iz arheloških uzoraka s područja Republike Hrvatske

master's thesis

• Title (english): Molecular and paleopathological analysis of possible cases of rheumatoid arthritis in human archaeological samples from Croatia
• Author: Andrea Gelemanović
• Mentor: Mario Šlaus (mentor)
• Mentor: Inga Marijanović (mentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Mario Šlaus (član povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Committee member: Mirjana Kalafatić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Reumatoidni artritis je autoimuna kronična bolest koja se očituje upalom sinovijalne ovojnice perifernih zglobova. Simetrično je distribuirana, najviše zahvaća zglobove šaka i stopala, a rezultira oštećenjem kosti i hrskavice što dovodi do invaliditeta. Etiologija reumatoidnog artritisa i dalje je nepoznata, no najvjerojatnije je rezultat interakcije genetičkih, infektivnih i okolišnih čimbenika. Prvi klinički zapis reumatoidnog artritisa u Europi potječe tek iz 1800. godine, no postoje dokazi da je bolest bila prisutna u Americi prije 6 500 godina. Na području Republike Hrvatske pronađena su dva srednjovjekovna ljudska posmrtna ostatka na čijim su se kostima primijetile patološke promjene karakteristične za reumatoidni artritis. Kako bi se bolest potvrdila, napravljena je molekularna analiza gdje se pokušalo dokazati prisustvo alela grupe HLA-DRB1*01 i HLA-DRB1*04 koji se povezuju s najvećim genetičkim rizikom za oboljenje od ove bolesti. Ekstrakcija drevne DNA napravljena je na nekoliko načina, uspješnost izolacije i kvaliteta izolirane DNA provjerena je kontrolnim reakcijama PCR, a tipizacija alela HLA-DRB1 napravljena je metodama PCR-SSP i PCR-SSO. Dobiveni rezultati upućuju da su osobe bile genotipa HLA-DRB1*01/*04 ili HLA-DRB1*01/*01. Ovo otkriće predstavlja prvi arheološki dokaz reumatoidnog artritisa na ovom području te potvrđuje da se bolest pojavila u Europi mnogo ranije nego se trenutno smatra.

Abstract (english)

Rheumatoid arthritis is an autoimmune chronic disease manifested by inflammation of the synovial membrane of peripheral joints. It is symmetrically distributed and mainly affects joints of hands and feet resulting in bone and cartilage damage leading to disability. Etiology of rheumatoid arthritis remains unknown, but most likely is the result of interaction of genetic, infectious and environmental factors. The first clinical record of rheumatoid arthritis in Europe originates from 1800s, but there is evidence that the disease has been present in America around 6,500 years ago. Two medieval human remains found in Croatia had skeletal pathological changes characteristic of rheumatoid arthritis. To confirm the disease, molecular analysis was performed to prove the presence of HLA-DRB1*01 and HLA-DRB1*04 group of alleles which are associated with the highest genetic risk. The extraction of ancient DNA was performed by several methods, the success of isolation and quality of the isolated DNA was estimated by control PCRs and HLA-DRB1 typing was done by PCR-SSP and PCR-SSO. The results indicate that their genotype was HLA-DRB1*01/*04 or HLA-DRB1*01/*01. This discovery is the first archaeological evidence of rheumatoid arthritis in this area and confirms that the disease appeared in Europe much earlier than is currently considered.

• Keywords: reumatoidni artritis; srednji vijek; drevna DNA; HLA-DRB1
• Keywords (english): rheumatoid arthritis; Middle Ages; ancient DNA; HLA-DRB1
• Language: croatian
• URN:NBN: urn:nbn:hr:217:322168
• 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: 2017-04-26 09:09:05