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Analysis of copy number variant (CNV) in genomes of patiens with mental retardation
Hančárová, Miroslava ; Sedláček, Zdeněk (advisor) ; Gaillyová, Renata (referee) ; Michalová, Kyra (referee)
Mental retardation (MR) is a very heterogeneous common neurodevelopmental disorder with a population prevalence of 2.5-3 %. The importance of genetic factors in the development of MR is high but in a significant number of cases the etiology remains unexplained. Recent studies using array methods pointed to frequent occurrence of copy number variants (CNVs) in patients with MR. Pathogenic CNVs were identified in 10-15 % patients with idiopathic MR and normal karyotype. The aim of our work was the analysis of genome-wide gains and losses of genetic material in a group of Czech patients with MR and a thorough bioinformatic analysis of the genetic changes identified aiming at the assessment of their clinical significance. We performed whole genome analysis using the HumanCytoSNP-12 BeadChips (Illumina) in 183 patients with idiopathic MR, normal karyotype and no FMR1 gene expansion. Data analysis was carried out using two independent programmes, GenomeStudio and QuantiSNP. The findings were subjected to two rounds of thorough bioinformatic analysis. Based on this analysis we classified the CNVs into 4 categories: pathogenic CNVs, probably pathogenic CNVs, CNVs with uncertain clinical significance and benign CNVs. With the exception of the benign variants, all CNVs were confirmed using an independent laboratory...
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Cryptic Rearrangements of Human Chromosomes Associated with Schizophrenia
Jurišová, Lívia ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Schizophrenia is a severe mental disorder with high heritability and complex genetics which interacts with environmental factors and leads to a wide range of symptoms. The emergence of modern cytogenetic and molecular genetic techniques has allowed uncovering one of the po- ssible causes - cryptic chromosomal rearrangements. The size of rearrangements, also known as microdeletions and microduplications, is under 3-5 Mb. Aberrations may affect multiple genes and their gene dosage. The research of cryptic rearrangements in association with schizophrenia began in 2008 with the identification of three pathogenic aberrations. Over time studies have identified more cryptic rearrangements and new studies supporting or not supporting their role in the disorder have been published. Research of the candidate genes and their possible interac- tions has also been conducted. It is hypothesized that schizophrenia is caused by pathologically changed brain connectivity, in which the changed gene dosage by cryptic rearrangements may play a role. The research is in its beginnings, and we can expect the identification of new rear- rangements. Further research may lead to a better understanding of the origin and symptoms of schizophrenia, and play a role in prenatal diagnostics and treatment. Key words: cryptic...
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Analysis of copy number variant (CNV) in genomes of patiens with mental retardation
Hančárová, Miroslava ; Sedláček, Zdeněk (advisor) ; Gaillyová, Renata (referee) ; Michalová, Kyra (referee)
Mental retardation (MR) is a very heterogeneous common neurodevelopmental disorder with a population prevalence of 2.5-3 %. The importance of genetic factors in the development of MR is high but in a significant number of cases the etiology remains unexplained. Recent studies using array methods pointed to frequent occurrence of copy number variants (CNVs) in patients with MR. Pathogenic CNVs were identified in 10-15 % patients with idiopathic MR and normal karyotype. The aim of our work was the analysis of genome-wide gains and losses of genetic material in a group of Czech patients with MR and a thorough bioinformatic analysis of the genetic changes identified aiming at the assessment of their clinical significance. We performed whole genome analysis using the HumanCytoSNP-12 BeadChips (Illumina) in 183 patients with idiopathic MR, normal karyotype and no FMR1 gene expansion. Data analysis was carried out using two independent programmes, GenomeStudio and QuantiSNP. The findings were subjected to two rounds of thorough bioinformatic analysis. Based on this analysis we classified the CNVs into 4 categories: pathogenic CNVs, probably pathogenic CNVs, CNVs with uncertain clinical significance and benign CNVs. With the exception of the benign variants, all CNVs were confirmed using an independent laboratory...
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