Research Information System
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey
Approval Date: 2017
Student: AYSEL ÜNAL
Supervisor: FERDA EMRİYE PERÇİN
Abstract:The human genome contains approximately 3,2 billion nucleotides. There are different size of variations between individuals which are the basis for phenotypic variations or may be the cause for diseases. Single nucleotide changes from the reference genome are called single nucleotide polymorphism (SNP), short (2-50 bases) deletions and insertions are named indels and chromosome changes greater than 50 bases are called copy number variation (CNV). As the importance of CNVs are recognized in diseases, methods for detecting them have increased to develop. Genome-wide or targeted methods are used in CNV studies. Array-based Comperative Genomic Hybridization (Array-CGH) and Single Nucleotide Polymorphism Array (SNP Array), chromosomal microarray as the general name, is suggested as the first choice diagnostic test in patients with intellectual disability, developmental delay and multiple congenital abnormalities. The standard method used in CNV detection today is array-CGH but it may lead to false positive results due to technical reasons. Therefore copy number changes that are thought to heve phenotypic effects need to be confirmed by a reliable method. In this study, it is aimed to demonstrate the reliability of a targeted CNV detection method, quantitative real-time PCR (qPCR) in validation studies and also to contribute to the literature by correlating the genotype / phenotype of specific microdeletion / microduplication syndromes confirmed. This study was a retrospective study evaluating 10 CNV regions of 10 patients who applied to Gazi University Medical Genetics Department due to intellectual disability and / or multiple congenital anomalies. After clinical evaluation, Array-CGH and then qPCR methods were applied to confirm the results. In the qPCR trial, 2 out of 10 CNVs were found to be false positive and 8 were successfully verified. Of the 8 confirmed CNVs, 4 were familial (3 maternal and 1 paternal) and 4 were novo. These results have shown that phenotypically important copy number changes detected in the array CGH should be confirmed with a second method and together with reliability studies in the literature, qPCR is a safe method for this purpose. Verification studies in conjunction with parents has contributed to the pathogenicity assessment of CNVs and provided a more accurate genetic counseling. It is also thought that this study will contribute to the literature with genotype/ phenotype correlation of HTR7, CDC16, OPHN1, GLRA1, ATP6AP2 genes the confirmed microdeletions / microduplications.