Molekularna istraživanja haplotipova HLA-DRB1*03-DRB3 u Hrvatskoj

master's thesis

• Title (english): Molecular analysis of HLA-DRB1*03-DRB3 haplotypes in the Croatia
• Author: Jelena Jakupić
• Mentor: Zorana Grubić (mentor)
• Mentor: Ana Galov (mentor)
• Committee member: Ana Galov (predsjednik povjerenstva)
• Committee member: Mirta Tkalec (član povjerenstva)
• Committee member: Renata Matoničkin Kepčija (član povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2016-12-09, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

U radu je istražena raznovrsnost haplotipova HLA-A-B-DRB1*03:01 i haplotipova HLA-DRB1*03:01-DRB3 u Hrvatskoj. Prva ispitivana skupina obuhvatila je 157 obitelji u kojima je jedan od roditelja bio pozitivan za alel HLA-DRB1*03:01 i unutar kojih smo segregacijom pratili nasljeđivanje haplotipova HLA-A-B-DRB1*03:01. Druga skupina obuhvaćala je 73 zdrava nesrodna ispitanika pozitivna za alel HLA-DRB1*03:01, koji su testirani za gen HLA-DRB3. Svim ispitanicima uključenim u istraživanje određeni su aleli lokusa HLA-A, -B i -DRB1 metodom lančane reakcije polimerazom i sondama specifičnim za alel/alele pojedinog lokusa HLA (PCR-SSO), dok su aleli lokusa HLA-DRB3 određeni metodom lančane reakcije polimerazom i početnicama specifičnim za alel/alele (PCR-SSP). Alel HLA-DRB1*03:01 pokazao je snažnu neravnotežu udruživanja s alelom HLA-B*08:01, a najčešći haplotip bio je HLA-A*01:01-B*08:01-DRB1*03:01 (47,8%). Uočena su dva alela na lokusu HLA-DRB3 (DRB3*01:01:02 i DRB3*02:02:01:01; 67,1% i 32,9%). Kod 92,7% ispitanika pozitivnih za alel HLA-B*08:01 bio je prisutan alel HLA-DRB3*01:01:02 (p<0,001). Na kombinaciju HLA-DRB1*03:01-DRB3 utječe prisustvo/odsustvo alela HLA-B*08:01, dok aleli HLA-A nemaju utjecaj.

Abstract (english)

In the present study the diversity of HLA-A-B-DRB1*03:01 and HLA-DRB1*03:01-DRB3 haplotypes in the Croatian population was analyzed. The first tested group included 157 families in which at least one parent was positive for HLA-DRB1*03:01 allele. HLA-A-B-DRB1*03:01 haplotypes were determined by segregation analysis. The second group included 73 unrelated healthy subjects positive for HLA-DRB1*03:01 allele, who were further analyzed for polymorphism of HLA-DRB3 gene. All subjects were tested for HLA-A, -B and -DRB1 alleles by Polymerase Chain Reaction - Sequence Specific Probes (PCR-SSO) method, while HLA-DRB3 alleles were identified by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) method. The HLA-DRB1*03:01 allele exhibited strong linkage disequilibrium with HLA-B*08:01 allele, while the most frequent haplotype was HLA-A*01:01-B*08:01-DRB1*03:01 (47.8%). Two alleles were detected at HLA-DRB3 locus (DRB3*01:01:02 and DRB3*02:02:01:01; 67.1% and 32.9%, respectively). A total of 92.7% HLA-B*08:01 positive subjects were also positive for HLA-DRB3*01:01:02 allele (P<0.01). Combination of HLA-DRB1*03:01-DRB3 haplotype is associated with presence/absence of HLA-B*08:01 allele, while HLA-A alleles don't have any influence.

• Keywords: geni HLA; polimorfizam gena HLA-DRB3; haplotipovi HLA; genska neravnoteža udruživanja
• Keywords (english): HLA genes; polymorphism of HLA-DRB3 gene; HLA haplotypes; linkage disequilibrium
• Language: croatian
• URN:NBN: urn:nbn:hr:217:431457
• 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
• Created on: 2017-05-05 11:51:57