Točkaste mutacije i bolesti

undergraduate thesis

• Title (english): Point mutations and diseases
• Author: Adriana Bobinec
• Mentor: Mirjana Pavlica (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2010, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Mutacije su nasljedne i trajne promjene u strukturi DNA molekule. Mutacije nastaju spontanim greškama tijekom replikacije DNA ili mogu biti inducirane nekim mutagenim agensima. Točkaste mutacije su mutacije koje nastaju supstitucijom jedne baze ili jednog baznog para drugim baznim parom i uzrok su brojnim bolestima. Prva bolest za koju je otkriveno da ju uzrokuje jedna točkasta mutacija je bila anemija srpastih stanica. Ova bolest uzrokovana je jednom točkastom mutacijom u ß globinskom lancu hemoglobina što za posljedicu ima abnormalne, rigidne eritrocite. To ima ozbiljne i često smrtonosne posljedice za bolesnika. No pojava ove mutacije u subtropskim i tropskim područjima dala je evolucijsku prednost osobama koje ju nose. Naime heterozigoti za ovu mutaciju imaju selekcijsku prednost budući da ne oboljevaju od malarije koja je česta upravo u tim područjima. Točkaste mutacije koje zahvaćaju mitohondrijsku DNA nasljeđuju se samo majčinskom linijom i uglavnom zahvaćaju kodirajuću DNA budući da mitohondriji ne sadrže introne kakvi su prisutni u genomu jezgre eukariota. MELAS sindrom i Leberova nasljedna optička neuropatija su primjeri bolesti uzrokovanih točkastim mutacijama u mtDNA. MELAS sindrom je teška i smrtonosna bolest uzrokovana defektnim proteinima koji grade kompleks I u mitohondriju i posebice pogađa tkiva poput mozga i mišića koja najviše ovise o staničnom ATP-u nastalom procesom oksidativne fosforilacije u mitohondrijima. Leberova nasljedna optička neuropatija za posljedicu ima potpuni gubitak vida kod vrlo mladih osoba. Veliki izazov za istraživače danas predstavlja otkrivanje novih metoda za detekciju točkastih mutacija, kao i različitih metoda njihovog liječenja odnosno smanjivanja negativnog učinka po stanicu i organizam primjerice pomoću genske terapije.

Abstract (english)

Mutations are hereditary and permanent changes in DNA structure. Mutations can occur spontaneously during DNA replication or they can be induced by mutagenic agents. Point mutations are a type of mutation that causes the replacement of a single base nucleotide with another nucleotide in DNA and they are responsible for many diseases. Sickle cell anemia was the first disease known to be caused by one point mutation. The cause of this disease is one point mutation in ß globin chain of hemoglobin which leads to formation of abnormal erythrocytes and that often includes severe and lethal consequences for the patient. Occurance of this mutation in tropic and subtropic areas, where malaria is also very common, made persons who were heterozygous for sickle cell anemia better adapted because this way they had much greater chance of surviving malaria. Point mutations that occur in mitochondrial DNA (mtDNA) are inherited only by mother line and since mitochondrion does not have intrones similar to those in nuclear genome of eucaryotes, these mutations usually affect coding region of mtDNA. Examples of such diseases are MELAS syndrome and Leber's hereditary optic neuropathy. MELAS syndrome is a severe and lethal disease caused by defect in proteins that build complex I in mitochondrion. It specially affects brain and muscle tissue which mostly depend on cell's ATP produced during the process of oxidative phosphorylation in mitochondrion. Leber's hereditary optic neuropathy causes complete loss of vision and it affects very young persons. Today researchers aim to find new methods for point mutations detection. They are also trying to discover various other methods of point mutations threatment like gene therapy. These methods help reduce negative effects of mutations on cells and organisms.

• Keywords: mutacije; točkaste mutacije; bolesti
• Keywords (english): mutations; point mutations; diseases
• Language: croatian
• URN:NBN: urn:nbn:hr:217:601618
• 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: 2018-03-22 09:20:13