Izdelava podatkovne zbirke kandidatnih lokusov za reprodukcijo pri moškem spolu sesalcev

Traven, Eva (author), Kunej, Tanja (mentor)

Pri 15 do 30 odstotkih moške neplodnosti so razlog genetske nepravilnosti in vplivajo na hormonsko ravnovesje, spermatogenezo in kvaliteto sperme. Najpogosteje poročani genetski vzroki so mutacije kromosomov Y, X in mtDNA ter spremembe na epigenetski in proteinski ravni. Kljub povečevanju števila objav, podatkov in različnih tipov lokusov, povezanih z neplodnostjo, da sedaj še niso bili postavljeni standardi za poročanje v znanstveni literaturi, kar bi lahko bistveno pripomoglo k razvoju področja in hitrejšemu odkrivanju biooznačevalcev. Namen magistrske naloge je zato bil zbrati genomske lokuse, povezane z moško neplodnostjo pri sesalcih in razviti podatkovno zbirko. Zbrali smo 1521 lokusov iz študij, ki so bile izvedene pri devetih vrstah: človek, pes, prašič, govedo, jak, ovca, zajec, podgana in miš. Zbrani podatki so bili dopolnjeni z relevantnimi genomskimi informacijami za posamezen metodološki pristop. Na osnovi urejenih podatkov smo nato oblikovali pobudo za poenotenje prikaza rezultatov v znanstveni literaturi, ki že služi kot vzorec za objavljanje v znanstveni reviji Systems Biology in Reproductive Medicine. Z analizo genomske razporeditve lokusov, povezanih z moško neplodnostjo, smo določili 15 novih kandidatnih regij AZF (angl. azoospermia factor), ki obsegajo manj kot 1,6 Mbp in vsebujejo vsaj tri lokuse. Z uporabo bioinformacijskih orodij smo za lokuse pri človeku identificirali značilno povezane biološke poti, bolezni in sindrome. Izdelali smo set 24 prednostnih SNP-jev, ki se nahajajo znotraj kandidatnih avtosomnih AZF regij in predstavljajo osnovo za razvoj seta za tarčno sekvenciranje (angl. targeted resequencing panel). Razvita podatkovna zbirka in pobuda za poenotenje poročanja povezav med genotipom in fenotipom v znanstveni literaturi predstavlja pomemben prispevek k razvoju sistemskih pristopov na področju reprodukcije pri moškem spolu sesalcev.

• Language: Slovenian
• Keywords: genetika, genomika, epigenetika, moška neplodnost, sesalci, reprodukcija, proteini
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Publisher: [E. Traven]
• Year: 2017
• PID: 20.500.12556/RUL-94345
• UDC: 575.112:004:577.213(043.2)
• COBISS.SI-ID: 8761209
• Publication date in RUL: 31.07.2017

Secondary language

• Language: English
• Title: Development of database of candidate loci for male reproduction in mammals

Abstract

Genetics abberations are the cause of 15 to 30 percent of male infertility cases. They interfere with hormonal balance, spermatogenesis and sperm quality. Mutations of Y chromosome, X chromosome and mitochondrial DNA and changes at the epigenetic and protein levels are most commonly reported genetic causes of male infertility. Despite increasing number of publications, data and different types of loci, linked to male infertility, until now there has been no initiative to standardize reporting and compiling the data to a database, which would greatly contribute to the development of the area and faster discovery of biomarkers. The purpose of the master's thesis was therefore to collect genomic loci associated with male infertility in mammals and to develop a database. We collected 1521 loci from studies that were carried out in nine species: human, dog, pig, cattle, yak, sheep, rabbit, rat and mouse. The collected data were supplemented with relevant genomic information for each methodological approach. Based on the collected data we designed an initiative for reporting standardization of the results in the scientific literature in the field of male infertility, which already serves as a template for publication in the scientific journal Systems Biology and Reproductive Medicine. Analysis of genomic distribution of loci associated with human male infertility revealed 15 new candidate autosomal AZF regions (azoospermia factor), which comprise less than 1,6 Mbp and contain at least three loci With the use of bioinformation tools, we identified biological pathways, diseases and syndromes associated with loci in human. We proposed a list of 24 priority SNPs located within candidate autosomal AZF regions which present a baseline for development of a targeted resequencing panel. The developed database and the initiative for reporting standardization of associations between genotype and phenotype in scientific literature presents an important contribution to the development of systemic approaches in the field of male infertility in mammals.

• Keywords: genetics, genomics, epigenetics, male infertility, mammals, reproduction, protein