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The hereditary sensomotoric neuropathy.
Jelínková, Zora ; Daňková, Pavlína (advisor) ; Šolc, Roman (referee)
Hereditary motor and sensory neuropathy (in short HMSN or hereditary sensomotoric neuropathy) also known as Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases which are the most frequent disorders affecting peripheral nervous system. The prevalence of these illnesses is generally 5 - 40 people per 100 000 inhabitants. CMT was first described in the 1886. Because of a large number of various types of mutations classification of HMSN is disunited. The main division of CMT depends on the median motor conduction velocity (and also on the part of nerve that was damaged). It is demyelinating (CMT 1) type and axonal (CMT 2) type. Further classification depends on the mode of heredity and phenotypic expression. Autosomal dominant CMT are divided into four main types - CMT 1A to D. Similar, CMT 2 could be distinguished by genetical subtype as well or, the classification can follow phenotypic expression. Beside the autosomal inherited HMSN, other types of hereditary sensomotoric diseases do exist: intermediate CMT, X-linked CMT, Déjerine-Sottas syndrom, congenital hypomyelination neuropathy and hereditary neuropathy with liability to pressure palsy. Individual types of HMSN are caused by mutations in various genes that are localized on different chomosomes. The...
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Significance of repetitive sequences in clinical and forensic genetics
Cerovská, Ela ; Daňková, Pavlína (advisor) ; Šolc, Roman (referee)
Repetitive sequences are important compartments of the genome and they are important for the whole organism as well. These non-coding sequences take a lot of space in the genome and they are called "junk DNA". However, they are valuable in many science sectors, especially because of their polymorphic character among individuals and also among tissues of one individual. This work pursues the significance of microsatellite repeats in clinical and forensic genetics. Some tumors have microsatellite instability (MSI) when compared to the repeats in the healthy tissue. This can be used to diagnose cancer. MSI sometimes appears before the disease fully breaks out, which could lead into an early diagnosis of cancer. MSI is associated with better prognosis. Forensic genetics takes advantage of microsatellite polymorphism among individuals. DNA profiling is used to identify persons in criminal investigations but also in parental testing or protection of wild animals.
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Molecular genetics of celiac disease
Němečková, Iva ; Daňková, Pavlína (advisor) ; Tučková, Ludmila (referee)
Celiac disease is an organ-specific autoimmune disease that arises as a consequence of hypersensitivity to the grain gluten in genetically susceptible individuals. Genetic predisposition are HLA-DQ2 and HLA-DQ8 genes, which are necessary but not sufficient for the emergence of celiac disease; it is involved in approximately 40% of the inheritance. In the course of the time, other genes that might contribute to the pathogenesis of celiac disease are being discovered. Among these so-called candidate genes, which are sought on the basis of known knowledge of molecular mechanisms of innate and adaptive immune responses, are for example: MIC, TNF, CTLA-4, CD28, ICOS, MYO9B, MMP, TLR and PTPN22. Immune response triggered by gluten peptide penetration into the lamina propria leads to mucosal damage. Different gluten peptides are involved in the pathology of celiac disease in different ways, some peptides trigger an adaptive immune response, while others, such as peptide p31- 43, triggers an innate immune response.
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Association of HSP70 genes with idiopathic inflammatory myopathy in a homogeneous cohort of Czech patients
Svitálková, Táňa ; Novota, Peter (advisor) ; Daňková, Pavlína (referee)
MHC complex is the most polymorphic, most complex and one of the most important parts of a genome which takes a part in the immunity response of an organism. In a human body, it is tagged as HLA (human leukocyte antigen) and consists of 224 genes. HLA genes are associated as a risk factor in numerous autoimmunity diseases. One of systemic autoimunity diseases is idiopathic inflammatory myopathy. It is a disease with a clinical manifestation of a chronical muscle inflammation with a destruction of own cells and leading to a damage of the whole organs. IIM involves several diagnoses - polymyopathy (PM), dermathomyopathy (DM) myopathy associated with tumor diseases (CDM) myopathy with inflammatory inclusion corps (IBM) and others. MHC complex consists of three parts, two of which - MHC class I and II - are already examined rather well and have been associated with numerous (mainly autoimmunity) diseases. Last part of MHC is located between class I and II is an area of around 150 genes called "non Class I/II" (Remáková, Novota, 1999). The main subject for my thesis are three genes of the HLA complex in which has been proven a function in regulation mechanism of some autoimmunity diseases. These genes play a part in the immunity response, because they are able to stimulate the adaptive and native...
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Prolactin and circulating monocytes - their significance and function in pathogenesis T1DM. Study in vitro
Bencúrová, Dominika ; Daňková, Pavlína (advisor) ; Černá, Marie (referee)
Introduction: Type 1 diabetes mellitus (T1DM) is characterized by an absolute deficiency of the insulin-producing beta cells of the islets of Langerhans in the pancreas. Among mechanisms that lead to pathogenesis of T1DM, innate immunity including key cells monocytes are involved. Based on expression of CD14 and CD16 surface markers, monocytes are classified into three subtypes with different functions. In addition to other markers, monocytes express on their surface prolactin receptor (PRLR) and toll-like receptors (TLR), which induce inflammatory responses, and produce extrapituitary hormone prolactin (PRL) that affects immune response. The aim of thesis was to study an effect of exogenous prolactin on the immune responses of monocytes and to try to detect its possible role in the pathogenesis of T1DM. Material and Methods: In vitro cultivation and stimulation of monocytes derived from 10 patients with T1DM and 10 healthy controls. As stimulating agents were used PRL and/or lipopolysacharide (LPS). For determination of mRNA levels of the studied cytokines (TNF-α, IL-6, FOS, IRF-1), total RNA isolated from monocytes acquired by immunomagnetic separation has been quantified by using Real Time PCR. The expression of surface markers (CD14, CD16, PRLR) was detected by flow cytometry. For detection of...
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Glaucoma - family-based genetic analysis in relation to autoimmunity
Buchtelová, Aneta ; Daňková, Pavlína (advisor) ; Ďuďáková, Ľubica (referee)
Introduction: Recent findings about the pathogenesis of glaucoma have already demonstrated the presence of some specific autoimmune mechanisms. It has also been shown that autoimmune diseases often manifest in co-occurrence, such as celiac disease and type 1 diabetes mellitus or psoriasis. This association can be explained by sharing some of the risk variants of HLA molecules class II. Considering glaucoma an autoimmune disease, the question raises how the glaucoma genetic risk factors affect the phenotype of another autoimmune disease or vice versa, whether genetic risk variants associated for example with celiac disease can affect the glaucoma phenotype. Aims: The aims of this study were to i) identify possible genetic risk markers associated with the development of glaucoma, based on the available literature, and to map their occurrence among members of a three-generation family suffering from glaucoma and multiple autoimmune diseases, ii) find carriers of HLA-DQ2/DQ8 among the members of the same family, iii) verify whether an individual's genotype correlates with his/her phenotype, and iv) determine the potential effect of specific HLA alleles on the glaucoma phenotype. Material and methods: This study used DNA samples derived from 34 members of a three-generation family, in which coeliac...
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Study of placental specific microRNA expression in pacients with spontaneous preterm birth and preterm prelabor rupture of membranes
Vintrová, Iva ; Hromadníková, Ilona (advisor) ; Daňková, Pavlína (referee)
MicroRNAs (miRNAs) are small non-coding RNAs with a length of 18 to 25 nucleotides playing a pivotal role in post-transcriptional regulation of gene expression. There are miRNAs whose expression is limited to a certain tissue type and diseases which are characterized by a unique miRNA expression profile. I assumed spontaneous preterm birth (PTB) and preterm prelabor rupture of membranes (PPROM) would be characterized by a unique miRNA expression profile. I observed the gene expression of 15 placental specific miRNAs (miR-512-5p, miR-515-5p, miR-516b-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a-5p, miR-519d-3p, miR-519e- 5p, miR-520a-5p, miR-520h, miR-524-5p, miR-525-5p, miR-526a and miR-526b-5p) in placental tissue of pacients with PTB, PPROM and women with term in labor pregnancies (FG). PTB group consisted of 24 pacients, PPROM group of 75 pacients and FG group of 20 pacients. Quantitative real-time PCR was used to quantify gene expression. In the group of PTB pregnancies I identified 3 significantly upregulated miRNAs (miR-516b-5p, miR-519d-3p and miR-524-5p) and 4 miRNAs (miR-518b, miR-519a-5p, miR-520h and miR-526a) with a trend to upregulation compared to controls (FG). In the group of PPROM pregnancies I identified 3 miRNAs (miR-519d-3p, miR-520h and miR-256b-5p) with a trend to...
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Using of quantitative DNA method as a screening tool for effecient genotyping of samples in forensic DNA laboratory.
Koljenšič, Ivana ; Stenzl, Vlastimil (advisor) ; Daňková, Pavlína (referee)
Quantification of human DNA in forensic samples is an important step during STR profiling because the STR genotyping is sensitive to the quantity of DNA used in the PCR reaction. This study focuses on the importance of quantification in the entire process of genetic analysis. Two real time PCR platforms (Roche LightCycler480 System and ABI 7900 RT PCR) were used to compare two commercial kits in terms of DNA quantification. It was found out that accuracy of absolute quantification values in commercial quantification kits is strongly dependent on the construction of calibration curve. Especially low template DNA samples were used to assess whether QuantifilerTM or Plexor® HY System can determinate a minimum quantification value (cut off value) below which STR profiles would consistently fail to be detected. The usage of Plexor® HY System enabled to determine the cut off quantification value more exactly probably due to different molecular background and chemistry used in this kit. Reliability and other issues connected with cut off value are discussed. In order to better understand the relationship between the quantity of DNA and the number of detectable loci series the dilution experiment with standard DNA007 was done. Quantitative and qualitative consequences of input DNA amount in evaluation of...
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Human gut microbiome: Origin, ontogenetic development, diversity and its use in anthropology
Dvořáková, Barbora ; Daňková, Pavlína (advisor) ; Schierová, Dagmar (referee)
Human gut microbiome is a broad term encompassing all microorganismal life inhabiting the human gut. The bacteria living in the human gut represents the largest group of the human microbiome, make up the significant percentage of the human cellular composition and their genomes comprise a big part of the human genome. Gut microbiome has a significant role in human health and changes throughout the human life in reaction e.g. to change of diet and medical drug usage. This work pursues the acquisition and development of gut microbiome, the factors influencing its formation and diversity, and its use in anthropology.
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