Reevaluacija genetičkih nalaza dobivenih kromosomskim čipovima kod bolesnika s neurorazvojnim poremećajima

master's thesis

• Title (english): Reevaluation of genetic findings obtained by chromosomal chips for patients with neurodevelopmental disorders
• Author: Ana-Marija Bogner
• Mentor: Martina Rinčić (mentor)
• Mentor: Petra Korać (komentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Inga Urlić (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-25, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Genetički testovi u širokoj su upotrebi već dugi niz godina, ali uvođenjem genetičkih testova
visoke rezolucije nastala je prekretnica u medicinskoj genetici. Za ispitanike s neurorazvojnim
poremećajima najčešće korišteni genetički test u proteklom desetljeću je analiza kromosoma na
mikročipovima. Iako nam danas genetički testovi visoke rezolucije omogućavaju otkrivanje vrlo
malih promjena u ljudskom genomu, određivanje patogenosti detektiranih varijanti ostaje izazov
u donošenju dijagnostičkih odluka. Novim spoznajama dolazi do promjena u razumijevanja
ljudskog genoma zbog čega je interpretacija genetičkih nalaza podložna promjeni tijekom
vremena. Ovim radom detektirane su promjene u interpretaciji genetičkih nalaza dobivenih
kromosomskim mikročipovima kod ispitanika s neurorazvojnim poremećajima uzimajući u obzir
nove znanstvene spoznaje. Reevaluirani su rezultati inicijalno klasificirani kao varijante nesigurne
važnosti koristeći javno dostupne baze podataka. Optimiziran je hodogram reevaluacije podataka
i dobivena lista 29 potencijalnih kandidata gena koji su od kliničke važnosti za razvoj
neurorazvojnih poremećaja. Istraženi su biološki putevi u koje su geni-kandidati uključeni te je
zabilježena jedna lncRNA povišene razine ekspresije u mozgu. Ponovnom analizom podataka
uspostavljena je dosad nepoznata veza između detektiranih promjena u broju kopija DNA i
fenotipa na osnovi novih znanstvenih saznanja o ljudskom genomu.

Abstract (english)

Genetic testing has been widely used for many years, but introducing high-resolution genetic
methods made a turning point in medical genetics. For patients with neurodevelopmental
disorders, the most commonly used genetic test in the past decade has been chromosomal
microarray analysis. Although today's high-resolution genetic tests detect very small changes in
the human genome, determining the pathogenicity of detected variants remains challenging in
diagnostic decision-making. Accumulating information and a better understanding of the human
genome resulted in the interpretation of genetic findings being subject to change over time.
Considering new scientific knowledge, this work detected changes in the interpretation of genetic
findings obtained by chromosomal microarray in subjects with neurodevelopmental disorders. The
results initially classified as of uncertain significance have been re-evaluated using publicly
available databases. A workflow was optimized, and a list of 29 potential candidate genes
clinically relevant for neurodevelopmental disorders was obtained. The biological pathways in
which the candidates are involved have been investigated, and one lncRNA has been recorded with
elevated expression in the brain. Reanalysis of the data has established a previously unknown link
between the detected changes in DNA copy number and the phenotype based on new scientific
knowledge about the human genome.

• Keywords: promjene broja kopija; CNV; CMA; NDD
• Keywords (english): copy number variant; CNV; NDD; CMA
• Language: croatian
• URN:NBN: urn:nbn:hr:217:218150
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-16 10:11:24