magistrsko delo
Nina Rupar (Author), Matija Rijavec (Reviewer), Nataša Debeljak (Mentor), Tanja Kunej (Co-mentor)

Abstract

Eritrocitozo opredelimo kot povečano koncentracijo eritrocitov, kar se odraža v povišanem hemoglobinu in hematokritu. Glede na vzrok motnje, jo delimo na primarno, kadar se napaka pojavi v kostnem mozgu, in sekundarno, kadar razlogi izven kostnega mozga vodijo do povečane proizvodnje eritropoetina (EPO). Družinska eritrocitoza (DE) je oblika eritrocitoze, ki nastane zaradi prirojene genetske napake. Gen EGLN1 kodira protein PHD2, ki je eden izmed ključnih encimov poti zaznavanja kisika pri človeku. Različice gena EGLN1 povzročajo eritrocitozo tipa 3, za katero so značilne nizke do normalne vrednosti serumskega EPO. Naša raziskava je bila sestavljena iz dveh delov. Namen prvega dela je bila analiza gena EGLN1 in izdelava kataloga različic gena EGLN1 povezanih z DE. Namen drugega dela je bila vzpostavitev diagnostične metode za določitev različic gena EGLN1. Za izbrane regije gena EGLN1 smo optimizirali reakcijo PCR pri kontrolnih vzorcih in vzpostavljen protokol uporabili za pomnožitev DNA petih članov dveh družin s sumom na DE. Pri eni izmed družin smo odkrili različico gena EGLN1 c.471G>C (p.Gln157His) pri obeh bolnikih. Pri drugi družini pa smo pri obeh članih s sumom na DE odkrili različico EGLN1 c.1072C>T (p.Pro358Ser), ki ni bila prisotna pri zdravem članu družine. Za potrditev vpliva odkritih različic EGLN1 na funkcijo proteina so potrebne nadaljnje raziskave.

Keywords

družinska eritrocitoza;gen EGLN1;protein PHD2;pot zaznave kisika;različica gena;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL MF - Faculty of Medicine
Publisher: [N. Rupar]
UDC: 606:616.155.191:601.4:575.22(043.2)
COBISS: 207601411 Link will open in a new window
Views: 92
Downloads: 24
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Other data

Secondary language: English
Secondary title: Analysis of genetic variability of EGLN1 gene in familial erythrocytosis
Secondary abstract: Erythrocytosis is defined as an increased concentration of erythrocytes, reflected in elevated haemoglobin and haematocrit. It is divided into primary, where the defect occurs in the bone marrow, and secondary, where causes outside the bone marrow lead to increased erythropoietin (EPO) production. Familial erythrocytosis (FE) is a form of erythrocytosis that results from a genetic defect. The EGLN1 gene encodes the PHD2 protein, which is one of the key enzymes of the human oxygen sensing pathway. Variants of the EGLN1 gene result in erythrocytosis type 3, which is characterised by low to normal serum EPO levels. Our study consisted of two parts. The first part was aimed at analysing the EGLN1 gene and creating a catalogue of EGLN1 variants associated with FE. The second part was aimed at establishing a diagnostic method to identify EGLN1 variants. We optimised the PCR reaction for selected regions of the EGLN1 gene in control samples and used this protocol to amplify DNA from five members from two families with suspected familial erythrocytosis. In one of the families, we found the EGLN1 c.471G>C (p.Gln157His) variant in both patients. In the other family, we detected the EGLN1 c.1072C>T (p.Pro358Ser) variant in both members with suspected DE, which was not present in the healthy family member. Further studies are needed to confirm the influence of the detected EGLN1 variants on the function of the protein.
Secondary keywords: familial erythrocytosis;EGLN1 gene;protein PHD2;oxygen sensing pathway;gene variant;
Type (COBISS): Master's thesis/paper
Study programme: 0
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages: 1 spletni vir (1 datoteka PDF (XI, 46 str., [5] str. pril.))
ID: 25021676