Bioinformacijska funkcionalna analiza genov v ohranjenih regijah pri sesalcih

Kuhar, Nika (avtor), Kunej, Tanja (mentor)

Evolucijsko ohranjene genomske regije so deli genoma, katerih zaporedje se je skozi evolucijo med različnimi vrstami ohranilo v veliki meri nespremenjeno, kar nakazuje na njihov pomemben biološki pomen. Namen magistrskega dela je bil analizirati izbrane ohranjene genomske regije pri človeku, opredeliti gene, ki se v njih nahajajo, ter ovrednotiti njihove biološke funkcije, povezave z monogenskimi boleznimi ali drugimi fenotipi, ki vplivajo na razvoj, preživetje ali osnovne biološke procese. V analizo smo vključili 20 izbranih ohranjenih genomskih regij CE (angl. constrained elements) in sicer 10 najdaljših in 10 z najvišjimi vrednostmi evolucijske ohranjenosti GERP (angl. genomic evolutionary rate profiling). Z uporabo orodij Ensembl, NCBI in STRING smo opredelili gene, ki vsebujejo regije CE, ter njihove biološke funkcije, povezave z monogenskimi boleznimi pa smo preverili v podatkovnih zbirkah OMIM in ClinVar. Za vzročne različice, povezane z monogenskimi boleznimi, smo preverili tudi vrednosti GERP, pri izbranih različicah pa dodatno izvedli večvrstne poravnave genomov 92 vrst sesalcev. Iz zbirke MGD smo pridobili informacije o funkciji genov in njihovi povezanosti z letalnostjo. Analizirane regije CE se nahajajo v 17 genih, ki so vključeni predvsem v delovanje živčevja in mišic, razvoj organizma, uravnavanje izražanja genov ter celične procese, kot sta znotrajcelični transport in signalizacija. V genih VPS13D, TTN, MYORG, KMT2A, SACS in EXT1 se nahajajo vzročne različice, povezane z različnimi monogenskimi boleznimi. Nukleotidne poravnave so pri izbranih različicah pokazale dobro ujemanje zaporedij med vrstami sesalcev. Za 12 od 17 analiziranih genov je bila v predhodnih študijah pokazana letalnost pri miših. Rezultati kažejo, da se analizirane regije CE prekrivajo z geni, pomembnimi za različne temeljne biološke procese, pri nekaterih genih so bile ugotovljene tudi povezave z boleznimi in preživetjem organizma. Rezultati lahko v prihodnje prispevajo k boljšemu razumevanju funkcionalnega pomena CE regij ter olajšajo prepoznavanje potencialno pomembnih genov in različic.

• Jezik: Slovenski jezik
• Ključne besede: vzročne različice, bolezni, nukleotidna poravnava, ohranjene regije, podatkovne zbirke
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: BF - Biotehniška fakulteta
• Leto izida: 2026
• PID: 20.500.12556/RUL-190939
• Datum objave v RUL: 08.11.2026

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Bioinformatic functional analysis of genes in conserved genomic regions in mammals

Izvleček

Evolutionarily conserved genomic regions are parts of the genome whose sequences have remained largely unchanged among different species throughout evolution, suggesting that they have important biological roles. The aim of this master’s thesis was to analyse selected conserved genomic regions in humans, identify the genes located within these regions, and evaluate their biological functions and associations with monogenic diseases or other phenotypes affecting development, survival, or fundamental biological processes. The analysis included 20 selected constrained elements (CE), comprising ten of the longest elements and ten with the highest values of evolutionary conservation, measured using GERP (genomic evolutionary rate profiling). Using the Ensembl, NCBI, and STRING tools, we identified the genes containing CE regions and characterized their biological functions, while associations with monogenic diseases were investigated using the OMIM and ClinVar databases. For causal variants associated with monogenic diseases, GERP values were also examined, and for selected variants, multiple sequence alignments of genomes from 92 mammalian species were additionally performed. Information on gene function and their association with lethality was obtained from the MGD database. The analysed CE regions are located within 17 genes that are primarily involved in nervous and muscular system function, organismal development, regulation of gene expression, and cellular processes such as intracellular transport and signalling. Causal variants associated with various monogenic diseases were identified in the genes VPS13D, TTN, MYORG, KMT2A, SACS and EXT1. Nucleotide sequence alignments of selected variants showed a high degree of sequence conservation among mammalian species. Previous studies have demonstrated lethality in mice for 12 of the 17 analysed genes. The results indicate that the analysed CE regions overlap with genes involved in various fundamental biological processes, with associations with disease and organismal survival also identified for some genes. These findings may contribute to a better understanding of the functional significance of CE regions and facilitate the identification of potentially important genes and variants in future research.

• Ključne besede: causal variants, diseases, nucleotide alignment, conserved regions, databases