magistrsko delo
Iva Mencin (Author), Nataša Debeljak (Mentor), Nataša Debeljak (Thesis defence commission member), Tanja Kunej (Thesis defence commission member), Mojca Narat (Thesis defence commission member), Tadej Pajič (Thesis defence commission member), Tanja Kunej (Co-mentor)

Abstract

Družinska eritrocitoza je redka dedna bolezen, za katero je značilno povišano število rdečih krvničk, lahko tudi povišan hematokrit in hemoglobin. Bolniki s to boleznijo se srečujejo s simptomi, kot so glavoboli, slabosti, krvavitve iz nosu, tromboze in krvavitve, ki lahko vodijo tudi do smrti. Tumor-supresorski protein von Hippel-Lindau (VHL) je del kompleksa, ki sodeluje pri razgradnji proteinov, tudi transkripcijskega dejavnika endotelijske PAS domene, ki se aktivira ob pomanjkanju kisika. Različice nukleotidnega zaporedja v genu VHL lahko vodijo do razvoja družinske eritrocitoze tipa 2. V raziskavi smo v sodelovanju s Specializiranim hematološkim laboratorijem kliničnega oddelka za hematologijo, interna klinika Univerzitetnega kliničnega centra Ljubljana, postavili diagnostično metodo za analizo različic nukleotidnega zaporedja gena VHL povezanih z družinsko eritrocitozo. Optimizirali smo reakcijo PCR, pomnožili odseke gena VHL ter jih sekvencirali z metodo po Sangerju. Z novo razvitim diagnostičnim testom smo analizirali DNA štirih bolnikov z eritrocitozo neznanega vzroka. Na podlagi sekvenčnih reakcij smo ugotovili, da nihče od preiskovanih bolnikov nima različice nukleotidnega zaporedja v genu VHL. S tem smo pri izbranih bolnikih izključili bolezen družinsko eritrocitozo tipa 2. V prihodnje se bo uveden molekularno-genetski test v kombinaciji z drugimi testi ugotavljanja različic v genih, povezanih z družinsko eritrocitozo, uporabljal za rutinsko diagnostiko pri bolnikih z eritrocitozo neznanega vzroka.

Keywords

genetska variabilnost;družinska eritrocitoza;VHL;tumor-supresorski gen;dedne bolezni;različica nukleotidnega zaporedja;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL MF - Faculty of Medicine
Publisher: [I. Mencin]
UDC: 575.822:606:616.155.191-056.7(043.2)
COBISS: 8867193 Link will open in a new window
Views: 1445
Downloads: 543
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Other data

Secondary language: English
Secondary title: Analysis of genetic variability of tumor-supressor gen VHL in familial erythrocytosis
Secondary abstract: Familial erythrocytosis is a rare inherited disease characterized by an increased number of red blood cells, often also elevated hematocrite and hemoglobin. Patients have symptoms such as headaches, nausea, thrombosis and bleeding, which can lead to death. Von Hippel-Lindau tumor suppressor protein (VHL) is part of a complex involved in the degradation of proteins, including the Endothelial PAS domain-containing protein 1 transcription factor, which is activated in the presence of oxygen deficiency. Sequence variants in VHL gene can lead to the development of familial erythrocytosis type 2. In collaboration with the Specialized haematological laboratory of the Clinical department of hematology, internal clinic University Medical Centre Ljubljana, we established a diagnostic method for the VHL variants in patients with familial erythrocytosis. We optimized PCR, amplified fragments of VHL gene and sequenced then with Sanger method. The new diagnostic test was used to analyse four patients with unknown causes of erythrocytosis. Based on sequential reactions, we confirmed that none of the examined patients had a variation in the VHL gene and therefore we excluded familial erythrocytosis type 2. In the future, this molecular-genetic test, with other tests on different genes, could be used for routine screening of variants in patients with idiopathic erythrocytosis.
Secondary keywords: genetic variability;familial erythrocytosis;genetic diseases;single-nucleotide variant;
Type (COBISS): Master's thesis/paper
Study programme: 0
Thesis comment: Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages: XII, 43 f., [11] f. pril.
ID: 10914771