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Genetic study of obesity in children
Říhová, Aneta ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Obesity is multifactorial dissease. Genetics factors participate in its origin of 40-70% (Barsh et al., 2000). Incidence of obesity is associated with a number of complications, which affect quality of life and abbreviate its length. It is projected in constantly younger age and its prevalence in the world grows. Even though several hundred genetics markers associated with obesity have been described, we still do not know all causes, which complicates efficiancy of treatment. Subject of this study was research of selected genes and their polymorphisms: FABP2 (rs1799883) and PLIN (rs1052700 and rs894160). The aim was to establish association between genotypes and antropometric and biochemical parameters related to obesity in group of 299 children and adolescents aged 7-18 years. Next goal was to establish whether these polymorphisms affect success of reduction therapy. SNP associations with antropometric and/or biochemical parameters were evaluated for boys and girls separately. Observed genotype frequencies between sex did not differ and they were in accordance with those explored in other populations. In rs1799883 polymorphism neither association with measured anthropometric and biochemical parameters nor effect on weight loss during reduction therapy have been found. The TT homozygote subjects of...
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Immunogenetic and hormonal markers of predisposition to systemic rheumatic diseases particularly systemic lupus erythematosus
Fojtíková, Markéta ; Pavelka, Karel (advisor) ; Hrnčíř, Zbyněk (referee) ; Rovenský, Jozef (referee)
Fojtikova 2011 INTRODUCTION: Several factors like genetic susceptibility is required for systemic rheumatic diseases development. Immunomodulatory PRL effect supports autoimmunity. AIMS: 1. To detect the immunogenetic background (alleles HLA class I, II and microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene) of SLE and PsA. 2. To detect PRL serum and synovial fluid with regard to clinical and laboratory RA activity. 3. To find the role of the functional polymorphism -1149G/T SNP PRL of extrapituitary promoter of PRL gene in SLE, RA, PsA, SSc and inflammatory myopathies development. METHODS: Genetic analyses of pateints with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47) a DM (n=68) and 123 healthy individuals: PCR-SSP (HLA clase I and II), PCR-fragment analysis (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). In 29 RA a 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. RESULTS: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in Czech population. In SLE versus controls allele MIC-A5.1 was increased (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 increases the risk for SLE development, pc <0.000001; OR 9.71....
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Molecular aspects of calcium-phosphate metabolism in renal complications of diabetes mellitus.
Šimáková, Eva ; Černá, Marie (advisor) ; Zajíčková, Kateřina (referee)
Introduction: This thesis deals with the calcium-phosphate metabolism and its role in the development of chronic diabetic complications. It examines calcium sensitive receptor, which can be crucial in affecting calcium metabolism. Calcium-sensitive receptor may play a role in intracellular signaling and metabolic pathways that lead to cell proliferation and extracellular matrix early diabetic nephropathy. We investigated two polymorphisms of the gene for calcium-sensitive receptor (intron 4 and codon 990). Material and Methods: The study included 313 diabetic patients, 41 patients with type 1 diabetes, 106 patients with type 2 diabetes, 110 diabetic patients with type 2 diabetes who had diabetic nephropathy and 56 patients with renal failure non-diabetic (NDRD). It was also examined 72 non-diabetic patients with chronic renal failure (CKD) and 96 healthy blood donors (ZK). Classification of diagnoses is listed in the theory. DNA was isolated by QIAamp DNA Blood Mini Kit and salting method. The specific fragments of gene for the CaSR were amplified by PCR. For detection, restriction fragment length polymorphism and TaqMan probes were used. The expression levels of mRNA were determined by real-time PCR. Results: For the codon 990 polymorphism, we found statistical significance of the genotype frequencies (AA,...
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Epigenetic regulation of HLA class II genes and their role in autoimmune diseases.
Čepek, Pavel ; Kotrbová - Kozak, Anna Katarzyna (advisor) ; Horníková, Lenka (referee)
Abstract Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Its incidence in Europe is continuously rising. The highest T1D risk is associated with HLA (human leukocyte antigen) class II genes. HLA class II molecules play a key role in regulation of immune response. They contribute to the selection of T cell repertoire by presenting antigenic peptides to the CD4+ T lymphocytes. HLA class II expression is controlled by regulatory module that is situated 150 - 300 base pairs upstream of the transcription- initiation site in all HLA class II genes. Polymorphisms in this region are linked to some autoimmune diseases. There were identified several promoter alleles (named QAP) in the HLA DQA1 gene promoter region. Most of the polymorphisms appear to be conserved within haplotype. Individual QAP alleles may have a different promoter strength by which they influence expression of HLA DQA1 gene alleles. Promoter strength can be modulated by DNA methylation. Aims:Our aim was to define methylation profile of HLA DQA1 promoters and determine the mRNA expression of individual alleles of HLA DQA1 gene in T1D patients. The mRNA expression level of HLA DQA1 gene alleles was determined using quantitative PCR. Methods: 30 diabetic pacients (age range 21 to 76 years), were included in this pilot...
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Evolutionary implications of innate immunity receptors polymorphism
Bainová, Zuzana ; Vinkler, Michal (advisor) ; Zajícová, Alena (referee)
Interactions between hosts and their parasites are considered to be one of the major forces driving animal evolution. It can be assumed that the evolutionary changes will occur especially in host molecules directly involved in these interactions. The first line of host defense is formed by innate immunity receptors among which also pattern recognition receptors (PRRs) belong. PRRs detect the presence of parasites at the beginning of their invasion by binding characteristic structures of their bodies (so called pathogen-associated molecular patterns, PAMPs, e. g. lipopolysaccharide, flagellin or peptidoglycans) or abnormal self molecules (damage-associated molecular patterns, DAMPs, e.g heat shock proteins). Although this mechanism of immune system activation is based on the recognition of ligands that are relatively evolutionarily conservative in pathogens, growing body of evidence suggests that PRRs are highly polymorphic on both interspecific and intraspecific level. High frequencies of minority alleles can be observed in most populations studied. It has been proven that particular alleles of many PRRs may associate with increased or decreased resistance to various infectious or autoimmunity diseases. Relationship between polymorphic receptor and a disease could be the main force, which shapes the...
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Vliv struktury na magnetické vlastnosti vzácně zeminných intermetalických sloučenin.
Vališka, Michal ; Pospíšil, Jiří (advisor) ; Javorský, Pavel (referee)
Náplní této práce je zkoumání vlivu symetrie na magnetické vlastnosti a supravodi- vost vzácně zeminných intermetalických sloučenin. Byly úspěšně připraveny polykrys- talické vzorky sloučenin YIr2Si2, LaIr2Si2 a SmIr2Si2 a to v podobě vysokoteplotní i nízkoteplotní fáze. Nízkoteplotní fáze byla připravena žíháním, jehož korektnost byla potvrzena pomocí DTA analýzy. Složení obou polymorfních fází bylo potvrzeno pomocí EDX analýzy a pomocí práškové rentgenové difrakce. V případě YIr2Si2 byly mřížové parametry získané difrakcí srovnány s teoretickými výpočty s velmi uspokojivým souhlasem. Z analýzy měrných tepel vyplývá, že vysokoteplotní fáze YIr2Si2 je supravodivá při TSC =2,50 K a LaIr2Si2 při TSC =1,49 K. Nebyly nalezeny žádné stopy po supravodivosti nízkoteplotních fází obou sloučenin až do teploty 0,35 K. Tato měření byla podpořena výsledky teplotní závislosti elektrického odporu. V případě sloučeniny SmIr2Si2 byly pomocí analýzy měrného tepla nalezeny magnet- ické přechody při teplotách 1,7 K, 6,2 K a 18,8 K pro vysokoteplotní fázi a při 1,9 K, 6,1 K a 38,9 K pro fázi nízkoteplotní. Dále byl shledán náznak přechodu při teplotě nižší než 0,5 K a to v obou fázích. M·že se jednat o další magnetický pře- chod nebo jaderný Schottkyho příspěvek. Magnetismus obou Sm fází je dán charak- teristickým...
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The mitochondrial genome in the ontogenesis
Töröková, Petra ; Brdička, Radim (advisor) ; Černý, Viktor (referee)
The main goal of this study is the comparison of sequences of the HVRII region of the mitochondrial genome in the cord blood sample and the saliva sample of the same individual, taken at average ten years from his/her birth. It is known that during ontogenesis the human genome changes. All the more the mitochondrial genome which shows a higher mutation rate, and moreover it is not taken care of it by repair mechanisms. In older individuals, there was found a distinctive amount of mitochondrial variations cumulated in different tissues in the process of the ontogenesis. This study is focused on the detection of these changes already in younger individuals. The tissue-specific variability which is created during ontogenesis might have an adverse influence on all sorts of the mtDNA based studies. The samples were taken in two regions (Teplice / Prachatice) that differ in the pollution of environment. With regard to that, the samples with discovered changes were compared from the standpoint of the region, which they had come from, with the aim to prove the influence of environment on the mutagenesis of the mitochondrial DNA. Samples were also compared from the point of view of sex. Furthermore the variability of the collection of Czech population was evaluated and the estimation of the genetic...
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Cytogenetics of bed bugs (Cimicidae) as a model representative of true bugs (Heteroptera)
Sadílek, David ; Johnson Pokorná, Martina (referee) ; Vilímová, Jitka (advisor)
Cytogenetics of bed bugs (Cimicidae) as a model true bugs (Insecta: Heteroptera) The thesis provides current opinions about a phylogeny of bed bugs, family Cimicidae, and their classification within the order Heteroptera. There are briefly summarized cytological data about the order Heteroptera, known karyotypes of the cimicid subfamilies and introduction to cytogenetics of species Cimex lectularius Linnaeus, 1758. Heteroptera species differ from other organisms by holokinetic chromosomes, a character, in which quite frequently take place chromosomal fragmentation and fusion. Several families posses smaller pair of m chromosomes, which behave during meiosis differently from the other chromosomes. Diploid chromosomal number is extremely variable, it ranges from four (family Belostomatidae) to 80 chromosomes (family Miridae). The behavior of chromosomes in the family Cimicidae is very specific. Sex-chromosomes univalents are connected by thread-like collochores and form so-called pseudobivalents during achiasmatic post-reductional meiosis. Rare polymorphism in a number of X chromosomes occurs in Cimex lectularius populations. The diploid karyotype always consists of 26 autosomal chromosomes and at least two but up to 15 X chromosomes and one Y chromosome. The number of X chromosomes can be variable...
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Role of selected ABC transporters in breast cancer development
Perglerová, Karolína ; Stiborová, Marie (referee) ; Souček, Pavel (advisor)
Breast cancer is a leading cause of death among women in many countries. In the treatment of the breast cancer cytotoxic drugs (chemotherapy) are often used. Interindividual differences of drug response are an important cause of treatment failures. Bioavailability also depends on a major extent from the expression and activity of drug transport across biomembranes. In particular efflux transporters of the ATP-binding cassette family such as ABCB1, ABCC1 and ABCC2 have been identified as major determinants of chemoresistance in tumor cells. It was hypothesized that variance in the gene expression of membrane transporters and their genetic variance could explain at least in part interindividual differences of pharmacokinetics and clinical outcome of a variety of drugs. This thesis focuses on the functional significance of gene expression of ABCB1, ABCC1 and ABCC2 and single nucleotide polymorphisms in ABCC1 gene.
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The importance of predisposition examination of late Alzheimer´s disease using methods of molecular biology
KOPAČKOVÁ, Michaela
Alzheimer's disease is the most common type of dementia. It affects up to 70% of cases from approximately 38 million people worldwide suffering from some type of dementia. Alzheimer's disease usually affects patients over 65 years of age, however, there are exceptions. It is presumed that the number of people with Alzheimer's disease will grow constantly in the future too. Its etiopathogenesis is not yet fully understood, that is why it is important to investigate dementia further, whether in terms of specific environmental and genetic risk factors, or in view of the economic burden for the society. The presented bachelor's thesis summarises findings about Alzheimer's disease, its neurobiology, etiology, diagnostics and genetic predispositions, in particular the ApoE, APP, PSEN1 and PSEN2 genes. The presence of epsilon 4 gene allele for apolipoprotein E provably contributes to the increased risk of the late form of Alzheimer's disease. On the contrary, mutation in APP, PSEN1 and PSEN2 genes are connected with Alzheimer's disease with the early onset of the disease, before 65 years of age. The objective in the experimental part was to manage the practical isolation of DNA from peripheral blood and buccal swab, preparation and execution of PCR reaction, detection of PCR products by gel electrophoresis and independent examination of ApoE gene by a certified CVD StripAssay Kit from ViennaLab company (PentaGen). The work also includes the optimisation of another molecular genetic method for the detection of variant alleles of ApoE gene. This method was carried out by a certified DiaPlexQTM ApoE Kit from SolGent Co., Ltd. The principle of detection in this case is based on real-time PCR.
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