Primjena mikročipova u otkrivanju genetskih uzroka spontanih gubitaka trudnoća

master's thesis

• Title (english): Application of microarray in revealing of genetic causes of miscarriages
• Author: Lucija Kauf
• Mentor: Feodora Stipoljev (mentor)
• Mentor: Petra Korać (sumentor)
• Committee member: Petra Korać (predsjednik povjerenstva)
• Committee member: Silvija Černi (član povjerenstva)
• Committee member: Julija Erhardt (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Smatra se da kromosomopatije uzrokuju više od 70% spontanih gubitaka trudnoće. U cilju otkrivanja genetskih uzroka gubitaka trudnoća, provodi se citogenetska analiza, a unatrag nekoliko godina i komparativna genomska hibridizacija na mikročipu (a-CGH). Za razliku od klasične citogenetske analize, ova a-CGH ne zahtjeva kultivaciju tkiva, već samo DNA uzorka, koja se može izolirati iz nativnih tkiva. Rezolucija mikročipa je veća u odnosu na citogenetsku analizu te se mogu detektirati manje patološke promjene nego citogenetskom analizom. Cilj istraživanja bilo je utvrditi postojanje suptilnih patoloških promjena broja kopija koristeći metodu a-CGH kod uzoraka spontanih gubitaka trudnoće kod kojih je klasična citogenetska analiza pokazala normalan kariotip ili kromosomski poremećaj te udio patoloških molekularnih kariotipova kod uzoraka bez informacija o kariotipu. Procijenjeno je značenje rezultata citogenomske analize za daljnje planiranje potomstva kod pacijentica.
Od 30 uzoraka, citogenetska analiza dala je rezultat za 22, dok je pomoću a-CGH dobiven rezultat kod svih uzoraka. Ukupna učestalost kromosomopatija iznosila je 33.3%. U skupini s normalnim kariotipom koristeći a-CGH otkriven je jedan uzorak s patološkom promjenom broja kopija, a u skupini bez rezultata citogenetske analize utvrđena je učestalost kromosomopatija od 50.0%. Majke plodova sa strukturnom kromosomskom aberacijom imaju najveći rizik u daljnjem planiranju trudnoća.

Abstract (english)

Chromosomophaties are considered to cause more than 70% of pregnancy losses. To reveal genetic causes of pregnancy loss, cytogenetic analysis and, in the last couple of years, microarray (a-CGH) is used. In contrast to cytogenetic analysis, a-CGH doesn't require cell culture, but only DNA of the sample, that can be extracted from the native tissue. Resolution of a-CGH is enhanced compared to cytogenetic analysis, which enables detection of smaller pathogenic changes. This study aimed to determine the share of subtle pathologic copy number variations in samples where cytogenetic analysis showed normal karyotype or chromosomal abnormality, and the percentage of pathological molecular karyotypes in the samples with no information about the karyotype, using a-CGH. The relevance of the results of the cytogenomic analysis in future pregnancy planning was estimated.
Out of 30 samples, cytogenetic analysis gave results for 22, while a-CGH was successful in all of them. The overall frequency of chromosomophaties was 33.3%. In the samples with normal karyotype, there was one sample with pathologic CNV, while the frequency of chromosomophaties in the samples with no results of cytogenetic analysis was 50.0%. Mothers whose products of conception had structural chromosomal aberrations had the highest risk in future pregnancy planning.

• Keywords: a-CGH; spontani gubitak trudnoće; citogenetska analiza; kromosomske aberacije; varijante broja kopija
• Keywords (english): a-CGH; pregnancy loss; cytogenetic analysis; chromosomal aberrations; copy number variations
• Language: croatian
• URN:NBN: urn:nbn:hr:217:769961
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-09-27
• Created on: 2021-10-13 07:32:46