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Cryptic Rearrangements of Human Chromosomes Associated with Autism Spectrum Disorders
Křivánková, Anna ; Šolc, Roman (advisor) ; Růžičková, Šárka (referee)
Autism spectrum disorders (ASD) are heterogeneous group of neurodevelopmental disabilities characterized by antisociality and atypical behavioral patterns. Its etiology is very complex, autism is usually formed by combining many factors. One of the causes may be genetic (gene mutation). It is known about 450 candidate genes for ASD so far. Minority of these genes occur in loci which are affected by cryptic rearrangements. These rearrangements significantly contribute to manifestation of this disorder. Patologies they cause, lead to syndromes with high penetrance for ASD such as Angelman/Prader-Willi or DiGeorge syndrome. Other loci are found on chromosome 1, 2 or 16. Due to short time of studies of cryptic rearrangements, phenotypic variability and number of patients we can expect more researches in the future. These researches are expected not to overlook the impact of the aberrations on formation of autism spectrum disorders.
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Cryptic Rearrangements of Human Chromosomes Associated with Autism Spectrum Disorders
Křivánková, Anna ; Šolc, Roman (advisor) ; Růžičková, Šárka (referee)
Autism spectrum disorders (ASD) are heterogeneous group of neurodevelopmental disabilities characterized by antisociality and atypical behavioral patterns. Its etiology is very complex, autism is usually formed by combining many factors. One of the causes may be genetic (gene mutation). It is known about 450 candidate genes for ASD so far. Minority of these genes occur in loci which are affected by cryptic rearrangements. These rearrangements significantly contribute to manifestation of this disorder. Patologies they cause, lead to syndromes with high penetrance for ASD such as Angelman/Prader-Willi or DiGeorge syndrome. Other loci are found on chromosome 1, 2 or 16. Due to short time of studies of cryptic rearrangements, phenotypic variability and number of patients we can expect more researches in the future. These researches are expected not to overlook the impact of the aberrations on formation of autism spectrum disorders.
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Microduplications on human chromosomes
Štolová, Lucie ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Microduplications are small chromosomal aberrations, for whose detection it is necessary to use molecular cytogenetic methods (FISH, CGH) instead of common cytogenetic methods. Together with microdeletions, they are most often mediated by non-allelic homologous recombination during meiosis. They occur at many places in human genome and the duplications of some chromosomal regions are responsible for syndrome emergence. Some of the genes, that are included by microduplications, are dosage sensitive and they cause the pathological phenotype. As a result of development of molecular genetic methods and their usage in studies targeted on microduplications, it comes out, that presence of microduplications on the human chromosomes was undervalued, especially because of their minor clinical significance compared to microdeletions.
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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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Reciprocal microdeletion and microduplication on human chromosomes
Sluková, Lucie ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Nonallelic homologous recombination (NAHR) mediated by LCRs (low-copy repeats) produces chromosomal rearrangements in the human genome. Those rearrangements include microdeletion and microduplication. Those mutations cause a great number of syndromes and thus are studied along with its genesis. Studies are enabled by the development of methods, which are able to detect those cryptic aberrations, e.g. comparative genomic hybridisation (CGH). Nowadays scientists often come across the mirror phenotype of the already described microdeletion (microduplication) syndromes. The presence of the reciprocal microduplication (microdeletion), which afflicted a gene sensitive to gene dosage or other important region of the human genome, is discovered by a genomic analysis. The examples of those affected chromosomal regions (and associated diseases) are areas 1q21.1; 5q35.2-3 (Sotos syndrome); 7q11.23 (Williams-Beuren syndrome); 16p11.2 až 12.2 a 16p13.11; 17q11.2 (Neurofibromatosis type 1); 17p11.2-12 (CMT1A/HNPP) a 22q11.2 (DiGeorge syndrome and VCFS). Key words: microduplication; microdeletion; nonallelic homologous recombination (NAHR); comparative genomic hybridisation (CGH); mirror phenotype; reciprocal rearrangements.
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