Polimorfizam Y131H gena ALG6 u karcinomu dojke

master's thesis

• Title (english): Polymorphism Y131H in breast cancer
• Author: Iva Ruščić
• Mentor: Sandra Šupraha Goreta (mentor)
• Committee member: Sandra Šupraha Goreta (predsjednik povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Committee member: Toma Keser (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2017-07-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Urođeni poremećaji glikozilacije (CDGs) skupina su genskih poremećaja uzrokovanih nedostatnom sintezom ili procesiranjem glikoproteina. Do danas je poznato pedesetak poremećaja N-glikozilacije. Klinički je spektar sindroma CDG iznimno varijabilan, od poremećaja ograničenih na specifične organe do ozbiljnih multisistemskih poremećaja. Najčešći su tipovi urođenih poremećaja glikozilacije CDG-Ia i CDG-Ic. Tip Ia nastaje kao posljedica smanjene aktivnosti fosfomanomutaze 2 uslijed mutacija u genu PMM2, dok je CDG-Ic uzrokovan mutacijama u genu ALG6 koji kodira Man9GlcNAc2-PP-Dol α1,3-glikoziltransferazu. Pokazano je da je učestalost nositelja određenih mutacija, ali i bolesnika s CDG, specifična za pojedinu populaciju. Premda u Hrvatskoj nije otkriven nijedan bolesnik s CDG uzrokovanim poremećajem N-glikozilacije, svrha ovoga rada bila je ispitati genotip polimorfizma Y131H u genu ALG6 u hrvatskoj populaciji, s obzirom na njegovu visoku učestalost (6,7%). Za određivanje polimorfizma Y131H (391T>C u egzonu 5), korištena je metoda lančane reakcije polimerazom i SSCP analiza. Polimorfizam Y131H ispitivan je na zdravoj populaciji i u ispitanica oboljelih od karcinoma dojke, jer je dokazano da Y131H polimorfizam pogoršava kliničku sliku kompleksnih genskih bolesti, uključujući i tumore. SSCP analizom pri utvrđenim uvjetima uzorci su genotipizirani, međutim za pravilnu procjenu utjecaja ovog polimorfizma za ovakvu vrstu bolesti trebalo bi provesti dodatno sekvenciranje i obuhvatiti veći broj uzoraka.

Abstract (english)

Congenital disorders of glycosylation (CDGs) are a growing group of genetic disorders caused by a deficient assembly or processing of glycoproteins. About fiffty disease-causing defects in protein N-glycosylation are known so far. The clinical spectrum of the different types of CDGs discovered so far is variable, ranging from disorders restricted to specific organs to severe multisystemic disorders. The most common types of CDGs are CDG-Ia and CDG-Ic. Type Ia is caused by reduced N-glycosylation due to phosphomannomutase 2 deficiency as a consequence of mutations in PMM2 gene and CDG-Ic is caused by mutations in ALG6 gene, encoding Man9GlcNAc2-PP-Dol α1,3-glucosyltransferase. The frequencies of heterozygotes for specific mutations, as well as CDG patients are specific for every population. Until now no patient with CDG syndrome affecting N-glycosylation was detected in Croatia. The aim of this study was to determine various mutations/polymorphisms in ALG6 gene in complex disease as breast cancer. For determination of the frequencies of polymorphisms of ALG6 gene, Y131H (391T>C in exon 5, PCR-SSCP analysis was used. Resolution of Y131H polymorphism was determined by SSCP analysis but it can not be said that the worse clinical outcome is due to found mutated genotype. The results must be checked by automated sequencing to obtain eventual minor frequent variants and to look in much bigger population study to find the right answers.

• Keywords: CDG; slobodna cirkulirajuća DNA; polimorfizam Y131H; SSCP analiza
• Keywords (english): CDG; cell free DNA; Y131H polymorphism; SSCP analyses
• Language: croatian
• URN:NBN: urn:nbn:hr:163:469481
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-11-22 09:06:02