Mapiranje gena odgovornog za cističnu fibrozu i razvoj genske terapij

undergraduate thesis

• Title (english): Mapping of the gene responsible for cystic fibrosis and development of gene therapy
• Author: Bruno Blažević
• Mentor: Nenad Malenica (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-06, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Cistična fibroza je progresivna multisistemska monogenska autosomalna recesivna bolest. Lokus gena
odgovornog za razvoj cistične fibroze identificiran je analizom rodoslovlja obitelji s oboljelim
članovima, usporedbom obrazaca polimorfizma markera RFLP, kloniranjem regije s genom od interesa
metodama chromosome walking i chromosome jumping te identifikacijom kodirajućih sekvenci unutar
regije. Gen odgovorann za bolest nazvan je cistično-fibrozni transmembranski regulator provodljivost
(CFTR). Protein CFTR sudjeluje u aktivnom transportu kloridnih i hidrogenkarbonatnih iona kroz
staničnu membranu. Mutacije unutar gena CFTR smanjuju njegovu funkcionalnost i uzrokuju nastanak
cistične fibroze. Ovisno o utjecaju na biosintezu proteina CFTR, opisane mutacije podijeljene su u šest
klasa. Patofiziologija bolesti temelji se na poremećaju prijenosa vode kroz membranu uslijed
nefunkcionalnog transporta iona. Gusta izlučena sluz pogodna je podloga za naseljavanje
mikroorganizama te blokira mnoge provodne kanaliće u organizmu. Genska terapija nudi trajno
izlječenje cistične fibroze korekcijom genskog defekta gena CFTR. CRISPR-Cas sustav ili peptidne
nukleinske kiseline primjeri su uspješne genske terapije u eksperimentalnoj korekciji cistične fibroze te
su mogući oblici genske terapije koji će naći širu primjenu u liječenju

Abstract (english)

Cystic fibrosis is a progressive monogenic autosomal recessive disease with multisystem readings. The
locus of the gene responsible for the development of cystic fibrosis was identified by analyzing the
pedigree of a family with affected members, comparing patterns of polymorphism of RFLP markers,
cloning the region with the gene of interest using chromosome walking and chromosome jumping
methods and identification of coding sequences within the region. The gene responsible for disease is
named cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR protein participates in
the active transport of chloride and hydrogen carbonate ions through the cell membrane. Mutations
within the CFTR gene reduce its functionality and cause cystic fibrosis. Depending on the impact on
CFTR protein biosynthesis, mutations are divided into six classes. The pathophysiology of the disease
is based on the disruption of water transport through the membrane due to dysfunctional ion transport.
Thick secreted mucus is a suitable substrate for the settlement of microorganisms and blocks many
channels in the body. Gene therapy offers a permanent cure for cystic fibrosis by correcting the genetic
defect of the CFTR gene. The CRISPR-Cas system or peptide nucleic acids are examples of gene therapy
successful in the experimental correction of cystic fibrosis and are possible forms of gene therapy that
will find wider application in treatment.

• Keywords: cistična fibroza; gensko mapiranje; CFTR; genska terapija
• Keywords (english): cystic fibrosis; gene mapping; CFTR; gene therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:217:868505
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-26 12:51:25