National Repository of Grey Literature 41 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Genetic factors of progression of selected forms of chronicnephropathies.
Šafaříková, Markéta ; Reiterová, Jana (advisor) ; Brdička, Radim (referee) ; Gaillyová, Renata (referee)
Nephrotic syndrome is characterized by proteinuria, hypoproteinemia, edemas and hyperlipidemia. It occurs in primary (e.g. focal segmental glomerulosclerosis, FSGS or minimal change disease, MCD) and in secondary glomerulopathies (e.g. kidney amyloidosis). In primary forms, great attention is paid to the potential genetic background of the disease and due to new molecular genetic methods genes, whose mutations cause different nephropathies (e.g. ACTN4 or INF2) were identified. The aims of presented doctoral thesis were following. Firstly, to continue the mutational analysis of ACTN4 that was described in the author's diploma thesis in other glomerulopathies. Secondly, to implement the mutational analysis of INF2 and subsequently analyse this gene in patients with FSGS/MCD and in patients from special group characterized by positive family history for end stage renal disease (ESRD) in combination with advanced chronic kidney disease (CKD) or already developed ESRD at the time of diagnosis. Thirdly, mutational analysis of NPHS2 and TRPC6 (methods implemented in laboratory earlier) in selected patients from the special group. Finally, expression analyses of genes important for podocyte function or connected with human immune system. This part also verifies the applicability of NPHS2/SYNPO expression...
Y-chromosomal polymorphisms in the Czech population with focus on Moravian Valachs: evolutionary anthropology study.
Ehler, Edvard ; Vančata, Václav (advisor) ; Černý, Viktor (referee) ; Brdička, Radim (referee)
1 Abstract Aim: This study presents an evolutionary anthropology approach to the history of Moravian Valachs. The origins of Valach population are approached by evaluating the admixture event that marked the appearance of Moravian Valachs. Methods & data: Focus of my Ph.D. project lies on Y-chromosomal variation, using 12 Y-STR loci haplotype to compute population genetic statistics, to infer Y-chromosomal haplogroup information and to compare Moravian Valachs to other European populations. Admixture analysis was performed. Our data set contains haplotypic information from 44 populations with the total of 4757 individuals. Moravian Valachs are presented by 94 DNA samples. Results: Our data reveal a decreased genetic variability in Moravian Valachs compared to other Central European populations. This feature is most probably caused by isolation of Valach population. Multidimensional scaling and comparison of FST distances shows Valach population as related to populations from Poland, Romania and Macedonia. Shared haplotypes and AMOVA tests place the Valachs to the Central European region. Also admixture analysis, as well as demographic and historical data, stresses the influence of autochthonous population of Moravia in the forming of Moravian Valachs. Conclusion: Moravian Valachs represent a hybrid...
Using modern molecular-genetic methods in prevention, early diagnosis, prediction of therapy response and prognosis
Benešová, Lucie ; Minárik, Marek (advisor) ; Brdička, Radim (referee) ; Klepárník, Karel (referee)
55 5 Závěr V prezentovaných pracích jsme se zabývali vývojem a praktickou aplikací metod pro rychlou, citlivou, vysokokapacitní detekci molekulárních markerů u různých typů nádorových onemocnění. Vyvinuli jsme v této souvislosti dvě nové metodiky. První je založená na cyklujícím teplotním gradientu, který poskytuje efektivnější separaci DNA molekul a možnost opakovaného dávkování v jedné analýze a tedy výrazné zvýšení celkového počtu analyzovaných vzorků 1 . Druhá metodika založená na dynamickém značení DNA molekul interkalačním činidlem během elektroforetické analýzy odstraňuje potřebu fluorescenčně značených primerů a dělá tak analýzy finančně i prakticky dostupnějšími 3 . Obě tyto metodiky jsme následně použili při analýzách klinických vzorků pacientů s nádorovým onemocněním. Výsledky uvedených publikací zaměřených na klinické aplikace ukazují, že vyšetření molekulárních markerů zahrnující mutace, alelické ztráty a jednonukleotidové polymorfismy má široké uplatnění. Charakterizace vzorků kolorekta na molekulární úrovni, jehož optimalizaci jsme provedli, může mít význam při popisu stádia transformace adenomu v karcinom nebo při odhadu prognózy onemocnění na základě detekovaných typů mutací 2 . U pacientů s podezřením na karcinom pankreatu může molekulárně-biologické vyšetření v kombinaci s cytologickým...
Lineage plasticity of leukemic cells
Slámová, Lucie ; Mejstříková, Ester (advisor) ; Brdička, Radim (referee) ; Machová Poláková, Kateřina (referee)
So far, the lymphoid to myeloid lineage switch during the treatment of B cell precursor acute lymphoblastic leukemia (BCP ALL) was identified only rarely in patients with the MLL gene rearrangement. We discovered a novel BCP ALL subset switching to monocytoid lineage during an early phase of the treatment - swALL ("switching" ALL) with no MLL gene rearrangement. The proportion of swALL cases among BCP ALLs was unexpectedly high (3-4%). All swALLs have expressed the CD2 antigen (LFA-2). The upregulation of C/EBPα gene and hypomethylation of the CEBPA promoter were significant in blasts already at diagnosis, proceeding the lineage switch in the majority of the cases. SwALL patients were characterized by unique subpopulation of the cells coexpressing B lymphoid and monocytoid markers. Changes in the gene expression of M-CSFR, GM- CSFR and other genes accompanied the lineage switch. The lineage switch could be recapitulated in vivo and in vitro. Even if the children patient with swALL respond slowly to initial therapy, the prognosis is comparable to "other" BCP ALLs. Risk-based ALL therapy appears to be the treatment of choice for swALL. Powered by TCPDF (www.tcpdf.org)
Validation of High Resolution Melting (HRM) for the purpose of DNA diagnostics: mutation analysis of the cystic fibrosis gene and selected candidates genes of male intertility
Peldová, Petra ; Macek, Milan (advisor) ; Brdička, Radim (referee) ; Korabečná, Marie (referee)
During the last years we have observed a rapid development of molecular genetic diagnostics (DNA diagnostics). New methods and technologies are rapidly being introduced and the spectrum of genetic services is gradually extended. Since germline genetic tests might have lifelong influence health and quality of patient's life, all efforts should aim at improvement of the overall quality of provided diagnostic services. An increasing number of laboratories replace their "in-house" developed techniques by the commercial diagnostic assays, but they often modify manufacturer's instructions. Therefore, it is necessary to validate and verify all methods and techniques before their implementation into routine DNA diagnostics. In this thesis I have focused on evaluation and application of High Resolution Melting (HRM) in clinical diagnostic practice based on its comprehensive validation, according to the major international quality assurance standard ISO 15189. On the model of selected genes (BRCA1, MTHFR, CFTR) we have confirmed the high utility of HRM for mutation scanning of unknown variants, as well as genotyping of common variants. Concurrently, we have provided a list of methodical guidelines which could be applied for setting up HRM in other genetic laboratories and provided a diagnostic validation strategy for...
Genetické příčiny deficitu cytochrom c oxidázy u dětí
Vondráčková, Alžběta ; Tesařová, Markéta (advisor) ; Brdička, Radim (referee) ; Procházková, Dagmar (referee)
Mitochondria are the key source of vital ATP molecules, which are largely produced within cells by a system of oxidative phosphorylation (OXPHOS). Genetic defects affecting any of the components of the oxidative phosphorylation system or the structure and function of mitochondria lead to mitochondrial disorders, which occur at an incidence rate of 1 in 5000 live births. Cytochrome c oxidase (COX) is the terminal enzyme and electron acceptor of a respiratory chain that catalyses oxygen to produce a water molecule. In addition to complex I deficiency, isolated or combined COX deficiency is the most common respiratory chain defect in paediatric patients, and it can arise from mutations located either in mitochondrial DNA or in nuclear genes encoding the structural subunits or corresponding assembly factors of the enzyme complex. However, the molecular basis of COX deficiency remains elusive in many patients despite advances in the identification of an increasing number of mutations and genes involved in the disease. This thesis focuses on the identification of the genetic causes of mitochondrial diseases in a cohort of 60 unrelated Czech children with clinically and laboratory confirmed COX-deficiency. With the use of a high-resolution melting analysis mutation screen, four heterozygous sequence...
Mutation Screening in Familial Cardiovascular Diseases
Čapek, Pavel ; Brdička, Radim (advisor) ; Gregor, Pavel (referee) ; Baxová, Alice (referee)
Introduction: Hypertrophic cardiomyopathy is a congenital cardiac disease with autosomal dominant pattern of inheritance and incomplete penetrance. With the knowledge of the responsible genes, the ability to detect the underlying genetic change and with the study of functional analysis of defected protein, we might be able to determine whether specific genotypes lead to different phenotypes. Aims of Study: To comprehensively analyze the mechanism of genesis of hypertrophic cardiomyopathy in Czech patients afflicted with this disorder from molecular genetic point of view (MYH7, TNNT2 gene) to functional analysis of the 3D molecular model of defected β-myosin heavy chain protein in silico. Beside these aims of the study, the reduction of production of inflammatory aggregates in the cardiovascular system was studied in patients with type 2 diabetes mellitus. The reason of this study was to look into possibilities of therapeutical effect on selected cardiovascular risks in patients with hypertrophic cardiomyopathy simultaneously suffering from type 2 diabetes mellitus. Both of these groups of patients have substantially increased risk of cardiovascular diseases due to development of premature atherosclerosis. Material and Methods: A total of 170 probands were enrolled in this study of MYH7 gene. DNA...
The importance of Neolithic expansion in Central Europe - an assessment of phylogenetic age of mtDNA haplogroups in the Czech population.
Priehodová, Edita ; Černý, Viktor (advisor) ; Brdička, Radim (referee)
Agriculture, with different Neolithic cultures, starts in the Near East more than 10,000 years ago. This new way of life has very different archaeological manifestations that previous Mesolithic. After its Near Eastern emergence, the farming practices rapidly penetrated into southeastern Europe and the first signs of Neolithic in Central Europe are already 7,000 years old. It is being considered that the cultural innovations influenced demographic growth of the populations that have taken part in the Neolithic spread. In such situation, new mutations would have to fix and could form new specific haplogroups for Europe with ancestral ties to the Near East. Phylogeographic studies such as founder analysis of European and Near Eastern mtDNA sequences found that the European Neolithic component was enriched mainly by haplogroups J and T1, and that the genetic contribution of farming economy in European gene pool is about 10 - 20%. However, studies like these have not been yet realized in particular parts of Europe. The aim of this thesis is to disentangle the internal variability of Central European haplogroups J and T1 thought to be involved in the Neolithic demic diffusion. We classified these haplogroups from the HVS-I mtDNA sequences of 281 samples of the recent population of the Czech Republic. We...

National Repository of Grey Literature : 41 records found   1 - 10nextend  jump to record:
See also: similar author names
Interested in being notified about new results for this query?
Subscribe to the RSS feed.