Detection of benign copy number variation by chromosomal microarray in Croatian population

master's thesis

• Title (croatian): Detekcija benignih varijanti broja kopija analizom kromosomskih mikročipova u hrvatskoj populaciji
• Author: Lea Kordić-Gružić
• Mentor: Feodora Stipoljev (mentor)
• Mentor: Petra Korać (komentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Vlatka Zoldoš (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Zorana Grubić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Copy number variants are characterized by losses or gains of DNA sequences in a range from 50 base pairs (pb) up to several megabase (Mb) for each copy. The clinical significance of CNVs is classified according to the guidelines of the American College for Medical Genetics and Genomics. Benign copy number variants are widespread in the general population and have no clinical significance. As part of this research, a retrospective-prospective analysis was conducted based on results for 400 patients referred for diagnostic treatment for various types of neurodevelopmental disorders, in the period from September 2021 to May 2023. As part of the research, a register of benign CNVs of the Croatian population is established. The significantly higher frequency of benign CNVs on chromosome 14 (34.75% of the total number of variants) indicates a possible uniqueness within the Croatian population, while benign variants on chromosomes 13, 18 and 20 are almost absent. The distribution of duplications (72.55%) among 2288 variants is significantly more prevalent than deletions (27.45%). Benign variants encompassing segments or entire genes whose specific alleles are assocaited with different diseases (so called morbid genes) like FCGR3A, ATF6, TFG, NIPA1, TAP2, KANSL1 underscore the existence of non-clinically significant variations in coding and regulatory regions of the human genome. This registry represents an important resource not only for diagnostic purposes but also for future research on genomic variability in the Croatian population, providing a systematic insight into benign CNVs.

Abstract (croatian)

Varijante broja kopija (CNV) označavaju delecije ili duplikacije DNA veličine od 50 parova baza (bp) do nekoliko megabaza (Mb). Klinički značaj CNV-ova klasificira se prema smjernicama Američkog sveučilišta medicinske genetike i genomike. Benigne varijante broja kopija su raširene u općoj populaciji i nemaju kliničkog značaja. U okviru ovog istraživanja provela se retrospektivno-prospektivna analiza kod 400 pacijenata upućenih na dijagnostičku obradu radi različitih tipova neurorazvojnih poremećaja, u razdoblju od rujna 2021. do svibnja 2023. U sklopu istraživanja napravljen je registar benignih CNV-ova hrvatske populacije. Značajno veća učestalost benignih CNV-ova na kromosomu 14 (34.75% od ukupnog broja varijanti) ukazuje na moguću jedinstvenost unutar hrvatske populacije, dok su benigne varijante na kromosomima 13, 18 i 20 gotovo u potpunosti odsutne. Distribucija duplikacija (72,55%) među 2288 varijanti značajno prevladava u odnosu na delecije (27,45%). Benigne varijante koje sadržavaju dio ili cijele gene, čiji su specifični aleli povezani s različitim bolestima (tzv. morbidni geni) poput FCGR3A, ATF6, TFG, NIPA1, TAP2, KANSL1, pokazuju da unutar ljudskog genoma postoje različite varijante u kodirajućim i regulacijskim regijama koje nemaju klinički značaj. Ovaj registar predstavlja važan resurs ne samo za dijagnostičke svrhe već i za buduća istraživanja genomske varijabilnosti u hrvatskoj populaciji, pružajući povezan i sustavan uvid u benigne CNV-ove.

• Keywords: Benign copy number variants; registry; Croatian population
• Keywords (croatian): Benigne varijante broja kopija; registar; hrvatska populacija
• Language: english
• URN:NBN: urn:nbn:hr:217:405264
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-02-26
• Created on: 2024-03-13 12:14:35