Identifikacija potencijalnih genskih poremećaja u pozadini slučaja idiopatskog niskog rasta

master's thesis

• Title (english): Identification of potential genetic disorders in the background of idiopathic short stature
• Author: Magdalena Skupnjak
• Mentor: Gordan Lauc (mentor)
• Committee member: Gordan Lauc (predsjednik povjerenstva)
• Committee member: Sanja Dabelić (član povjerenstva)
• Committee member: Živka Juričić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2021-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

DNA kao temeljna molekula kojom se prenosi genetska informacija podložna je promjenama, a promjene patogenog značenja nazivamo mutacijama koje se u konačnici mogu odraziti i na fenotip. Polimorfizmi jednog nukleotida mogu utjecati na ekspresiju gena i funkcionalnost proteina tijekom i nakon njihove sinteze, što u konačnici rezultira određenim genetskim poremećajem. SNP-ove detektiramo analizom slijeda DNA, metodama kao što su Sangerovom dideoksi metodom, ali i GWAS studijama i obiteljskim studijama, a gdje se u pozadini svega koriste DNA-čipovi.
Tijekom rasta i razvoja, osim endokrine regulacije, za rast je bitna i lokalna regulacija rasta, te je cilj istraživanja je ispitati radi li se o monogenskom poremećaju ili je niski rast ispitanice posljedica poligenskih učinaka. Istraživanje bi također moglo doprinijeti boljem razumijevanju povezanosti signalnih puteva uključenih u rast i razvoj kao i njihove genske pozadine u različitim tkivima.
Pregledom literature i na temelju dobivenih rezultata pretpostavlja se da postoji multigenski učinak kao i da je u pozadini svega kadherin 13 koji pokazuje najsnažniju povezanost s genima na razini hipotalamusa kao centra za razvoj.
Pretpostavka je da je lokalno prisutan utjecaj gena na razvoj kostiju jer smo uspjeli povezati gene EHF i SPARC, ali i WWTR1 i SMARCA4 (iako za njih ne možemo sa sigurnošću tvrditi prisutnost SNP-va) sa RUNX2 koji je jedan od ključnih faktora osteogeneze u zoni rasta.

Abstract (english)

DNA as a basic molecule that transmits genetic information is subject to changes, and changes with pathogenic significance are called mutations that can ultimately affect the phenotype. Single nucleotide polymorphisms can affect gene expression and protein functionality during and after their synthesis, resulting in a specific genetic disorder. SNPs are detected by DNA sequence analysis, methods such as Sanger's dideoxy method, but also by GWAS studies and family studies, where DNA chips are used.
During growth and development, in addition to endocrine regulation, local growth regulation is also important, and the aim of the research was to examine whether it is a monogenic disorder or short stature of the subject is result of polygenic effects. Research could also contribute to a better understanding of the interconnections of signaling pathways involved in growth and development as well as their genetic background in different tissues.
A review of the literature and based on the obtained results, we are assuming that there is a multigenic effect and that in the background is cadherin 13 which shows the strongest association with genes at the level of the hypothalamus as a center for development.
It is assumed that the influence of genes on bone development is locally present because we managed to connect the genes EHF and SPARC, but also WWTR1 and SMARCA4 (although we cannot claim with certainty the presence of SNPs) with RUNX2 which is one of the key factors of osteogenesis in the growth plate.

• Keywords: DNA; mutacija; polimorfizam; niski rast
• Keywords (english): DNA; mutation; polymorphism; short stature
• Language: croatian
• URN:NBN: urn:nbn:hr:163:084786
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-11-15 16:45:15