Primerjalna analiza genetskih vzrokov za razvoj kriptorhizma pri sesalcih

magistrsko delo

Kristian Urh (Author), Jernej Jakše (Reviewer), Tanja Kunej (Mentor), Tanja Kunej (Thesis defence commission member), Alenka Hodžić (Thesis defence commission member), Mojca Narat (Thesis defence commission member), Jernej Jakše (Thesis defence commission member), Alenka Hodžić (Co-mentor)

Abstract

Kriptorhizem (CO) je urogenitalna anomalija, pri kateri se testis ne spusti skozi ingvinalni kanal v skrotum in se pojavlja tako pri človeku, kot drugih sesalskih vrstah. Povezan je z večjo verjetnostjo razvoja neplodnosti in tumorjev. Večina dosedanjih študij je bila usmerjena v analize posameznih genetskih vzrokov, manj pozornosti pa so raziskovalci posvetili urejanju podatkov ter bioinformacijskim analizam za identifikacijo zanesljivejših kandidatnih biooznačevalcev. Naloga je sestavljena iz treh sklopov: dopolnitev podatkovne zbirke lokusov za CO, bioinformacijske in eksperimentalne analize. Zbirka vsebuje 487 lokusov iz osmih sesalskih vrst, razporejenih glede na klinični podtip CO. Za človeka smo razvili obrazec za standardizacijo poročanja povezav med lokusi in CO v znanstveni literaturi. Izvedli smo tri bioinformacijske analize. Z identifikacijo najmanjših regij prekrivanja (angl. smallest region of overlap; SRO) smo določili 18 SRO-jev, ki vsebujejo 927 genov, od tega 60 genov za CO pri človeku in štiri pri drugih vrstah živalih. Razvili smo nov študijski pristop, ki smo ga poimenovali določanje SRO-jev na ravni celotnega genoma (angl. genome wide screening for SROs; GW-SROs). V obogatitveni analizi bioloških poti z orodjem DAVID smo na osnovi 281 genov za CO pri človeku določili 63 značilnih bioloških poti. V analizi interakcij med proteini z orodjem STRING smo določili pet modulov. V rezultatih vseh treh bioinformacijskih analiz se nahajajo štirje geni, ki so lahko zanesljivejši kandidati za CO. Z metodo aCGH smo identificirali 23 različic v številu kopij (CNV) v slovenski populaciji preiskovancev s CO in/ali neplodnostjo. V magistrskem delu smo z uporabo različnih pristopov analizirali povezave med genotipom in CO ter izpostavili kandidatne biooznačevalce za CO. Na podlagi rezultatov te študije bo v prihodnosti možno dodatno zožiti SRO-je, določiti nove kandidatne funkcionalne module za CO, in jih eksperimentalno preveriti pri človeku in ostalih vrstah sesalcev.

Keywords

nespuščeni testisi;kriptorhizem;sesalci;genetski vzroki;bioinformatika;

Data

Language:	Slovenian
Year of publishing:	2017
Typology:	2.09 - Master's Thesis
Organization:	UL BF - Biotechnical Faculty
Publisher:	[K. Urh]
UDC:	601.4:577.21:616.681:575.112(043.2)
COBISS:	8810105
Views:	4198
Downloads:	258
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Comparative analysis of genetic causes for cryptorchidism development in mammals
Secondary abstract:	Cryptorchidism (CO) is an urogenital anomaly, in which the testis does not descend through the inguinal canal into the scrotum and occurs in human, as well as in other mammalian species. It is associated with a higher probability of infertility and tumors. Most of the studies so far have been focused on identification of single loci genetic causes, while less attention has been paid to data editing and bioinformatics analyses for identification of reliable candidate biomarkers. The masters thesis contains three chapters; update of the database of CO loci, bioinformatics, and experimental analysis. The database consists of 487 loci from eight species, sorted according to the clinical biotype of CO. We have developed a standardized form for reporting of human loci associated with CO in the scientific literature. We performed three bioinformatics analyses. We have identified 18 smallest regions of overlap (SROs), that consist of 927 genes, including 60 human CO genes, and four in other species. We developed a new study approach, named genome wide screening for SROs; GW-SROs. In the pathway enrichment analysis using the DAVID tool we identified 63 significant pathways associated with 281 CO genes in human. In the protein interaction analysis using the STRING tool we identified five modules. Four genes which are present in the results of all three bioinformatics analyses can be considered as reliable candidates for CO. Using the aCGH method we identified 23 copy number variants (CNV) in the slovene population of patients with CO and/or infertility. In the masters thesis we have analysed genotype-CO associations using several approaches and prioritized candidate biomarkers for CO. Results of this study present a basis for further narrowing of SROs, identification of new candidate functional modules for CO, and their experimental validation in human and other mammalian species.
Secondary keywords:	undescended testes;cryptorchidism;mammals;genetic causes;bioinformatics;
Type (COBISS):	Master's thesis/paper
Study programme:	0
Embargo end date (OpenAIRE):	2018-09-04
Thesis comment:	Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages:	XV, 154 str., [32] str. pril.
ID:	10910285