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Uniparental disomy in the human karyotype
Koplíková, Patricie ; Drábová, Jana (advisor) ; Šípek, Antonín (referee)
Chromosome pairs affect how our body works. Normally, a baby gets one copy of each chromosome from each parent. This means one copy from mother, and the other copy from father. In rare cases, a baby may get two copies from the same parent and none from the other. This phenomenon is called uniparental disomy (UPD). Uniparental disomy is a major topic for molecular geneticists and cytogeneticists. There are several mechanisms that lead to UPD, for example: gamete complementation, monosomy rescue, trisomy rescue or post-fertilization error. The consequences of UPD can be diverse and depend on the specific chromosome and genetic content of the affected region. An abnormal phenotype is manifested if the UPD occurs on a chromosome that is subject to genomic imprinting. An abnormal phenotype can also occur due to mutations. Among the most common syndromes associated with UPD are Prader-Willi syndrome and Angelman syndrome, which I focus on in my theses. I consider the greatest contribution of my theses to be the creation of a comprehensive overview of the effects of UPD across all human chromosomes.
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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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Characteristic of chromosomal changes in nephroblastomas using SNP array and MLPA
Štolová, Lucie ; Vícha, Aleš (advisor) ; Daňková, Pavlína (referee)
Nephroblastoma is the most prevalent pediatric kidney tumor, which occurs primarily in younger children with the average age at diagnosis of 42,5 months for girls and 36,5 months for boys. Even though its treatment is currently very succesful and the overall survival rate reaches over 90 %, there are still more things to be discovered and improved. An important role for the right choice of treatment plays not only the histology of tumor, but also the chromosomal changes present at tumor. Some of them (for example 1q gain, simultaneous deletion of 1p and 16q, TP53 deletion) were confirmed as negative prognostic markers because they are associated with an increased risk of relapse or with anaplastic type of nephroblastoma that is included in a high risk group. These changes are therefore used together with the tumor histology for stratification of nephroblastomas. Some of these changes were found in a heterogeneous state (only in a part of the cells) in nephroblastoma, which also complicates the treatment of the patient and which cannot be solved when only one sample is taken from the tumor. In this work we concentrated on the detection of chromosomal changes present in nephroblastomas of 44 patients and their associations with clinical data. We have proved some of the known associations (22q...
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Analysis of clinical features in patients with autism and intellectual disability who were indicated to the investigation using SNP array
Petříková, Nikola ; Vlčková, Markéta (advisor) ; Panczak, Aleš (referee)
This bachelor thesis deals with the analysis of clinical features in patients with autism spectrum disorders who were investigated using DNA microarrays. The introductory section is focused on the definition of autism and its subtypes, on currently known genetic causes of this neurodevelopmental disorder and on the possibilities of the laboratory diagnosis. Autism is likely caused by CNV occurring in different loci of the human genome, which can be efficiently diagnosed using DNA microarrays. This technique enables the detection of many CNV, but in most cases only common population polymorphisms can be identified. Our group consisted of 98 patients who suffered from some subtype of autism spectrum disorder. All patients were investigated using the microarray HumanCytoSNP-12 manufactured by Illumina. A retrospective analysis of clinical features of interest that were found in the medical documentation of the patients was performed. Statistical analysis of the data was performed to find possible associations. Specific pairs of features were compared in more detail. Features with known correlation previously published in the literature or features where a correlation could be expected were selected for this detailed analysis. Some findings were concordant with the published data, but some were not. Finally, it...
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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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