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Pathological findings in pediatric patients detected by array-CGH
Šlégrová, Sandra ; Krkavcová, Miroslava (advisor) ; Panczak, Aleš (referee)
The thesis focuses mostly on discovering unrevealed causes of pathologic phenotype symptoms of patients with whom no pathologic changes in genetic material were detected by common cytogenetic methods. All samples were examined by a chip method array-CGH (comparative genomic hybridization) which detects aberrant spots without any knowledge of where they are located in the genome. In some cases the method was used to verify or specify the finding that was diagnosed during previous genetic testing. The patients were examined by this method in an accredited genetics laboratory GENvia, s.r.o. in 2013 and partly also in 2014. The theoretical part of the thesis focuses on the role of the common cytogenetic method and its diagnostic use. I also describe the basic principle of the array-CGH method and its use in prenatal and postnatal diagnostics. The practical part of the thesis describes results of all examined patients. But mostly it focuses on pediatric patients where the diagnosis correlates with their clinical symptoms. All the results were verified by another method used for the particular diagnosis. Some results were verified by FISH (fluorescence in situ hybridization) method, other ways of the results verification are described as well. In total 8 pathologic findings were discovered in patients up to 12...
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Variants of human chromosome 9 - from norm to pathology Epidemiology and significance for medical genetics.
Šípek, Antonín ; Panczak, Aleš (advisor) ; Šubrt, Ivan (referee) ; Vallová, Vladimíra (referee)
Heterochromatin variants of human chromosome 9 belong to the most common variabilities of human karyotype. The variability involves the large block of constitutive heterochromatin in the pericentric region of chromosome 9, which is composed of various types of repetitive DNA sequences. Those variants can be studied from population epidemiologic, molecular cytogenetic and clinical genetic point of view. We have performed a broad epidemiologic study of the incidence of pericentric inversion of chromosome 9 (inv(9)) and other variants of chromosome 9 in 6 different laboratory cohorts, which included the evaluation of more than 26.000 of cytogenetic reports, the study we published is currently the largest in the world. We expressed the overall incidence of inv(9) to be 1.6% and the total incidence of variants of chromosome 9 to be 3.3-3.9%. Inv(9) was more common in females, however the difference was not statistically significant. Molecular cytogenetic part of the project was based on our own diagnostic approach, which involved the combination of three different commercial FISH probes. Combination of those probes allowed us to differentiate particular subvariants of chromosome 9, which cannot be analyzed only by using G- or C-banding. Using our method, we tested 49 carriers of chromosome 9...
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Aspects of identification of patients with primary ciliary dyskinesia
Djakow, Jana ; Cinek, Ondřej (advisor) ; Vízek, Martin (referee) ; Panczak, Aleš (referee)
Primary ciliary dyskinesia (PCD) is a rare but underdiagnosed genetic disease. This innate disorder of motile cilia causes a non-functional mucociliary clearance which is the main reason for a clinical picture of recurrent or chronic upper and lower respiratory tract infections. Fertility disorders or abnormal organ situs can also be found in some patients. The diagnosis of PCD is extremely complicated and complex. A combination of several diagnostic procedures as well as skilled personnel and special technical equipment are usually needed for the PCD diagnostics. Although significant progress has been made in understanding the PCD etiopathogenesis and the advanced diagnostics has become available, therapeutic possibilities are rather limited and the treatment efficiency still remains to be confirmed by the evidence base medicine. The dissertation thesis assembles several publications in which different aspects of primary ciliary dyskinesia were addressed. The most extensive part of our research addressed rapidly evolving possibilities of PCD genetic diagnostics. We studied possibility of priority sequencing of several segments of the genes DNAH5 and DNAI1 which were known to be the most frequently mutated genes in the PCD patients at the time of the study. We proved this method being able to...
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Pathological findings in pediatric patients detected by array-CGH
Šlégrová, Sandra ; Krkavcová, Miroslava (advisor) ; Panczak, Aleš (referee)
The thesis focuses mostly on discovering unrevealed causes of pathologic phenotype symptoms of patients with whom no pathologic changes in genetic material were detected by common cytogenetic methods. All samples were examined by a chip method array-CGH (comparative genomic hybridization) which detects aberrant spots without any knowledge of where they are located in the genome. In some cases the method was used to verify or specify the finding that was diagnosed during previous genetic testing. The patients were examined by this method in an accredited genetics laboratory GENvia, s.r.o. in 2013 and partly also in 2014. The theoretical part of the thesis focuses on the role of the common cytogenetic method and its diagnostic use. I also describe the basic principle of the array-CGH method and its use in prenatal and postnatal diagnostics. The practical part of the thesis describes results of all examined patients. But mostly it focuses on pediatric patients where the diagnosis correlates with their clinical symptoms. All the results were verified by another method used for the particular diagnosis. Some results were verified by FISH (fluorescence in situ hybridization) method, other ways of the results verification are described as well. In total 8 pathologic findings were discovered in patients up to 12...
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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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Possibilities of assessment and the relevance of the results of FISH analysis of chromosomal abnormalities in mosaics
Neužilová, Linda ; Kočárek, Eduard (advisor) ; Panczak, Aleš (referee)
This bachelor thesis deals with mosaicism and its detection. Mosaicism is defined as the presence of two or more cell lines with different karyotype in the patient's body. An aspect of particular importance for the resulting phenotype is the overall ratio in which the individual cell lines are represented. It is often found in Turner and Klinefelter syndrome. Turner syndrome is caused by the loss of a part of, or the whole of the X chromosome in females and it belongs among the most common chromosomal constitutions, found in spontaneous abortions. However, it is estimated that only about half of the women with Turner syndrome have karyotype 45,X; the others are mosaics or have other abnormalities of the chromosome X. The main aim of the practical part of this thesis was to evaluate the possibilities of detecting mosaicism using fluorescence in situ hybridization (FISH) and to consider the possible factors affecting the accuracy of the examination. The objectives of the assessment were the individual variability between the evaluators and also the differences caused by using two differently labelled probes. As a result, the thesis confirms that the FISH method enhances the accuracy of the results of conventional cytogenetic examination and it is suitable for analysis of mosaicism thanks to the possibility of...
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