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Dwarfism. Pathogenesis with a special focus on genetic factors.
Procházková, Lucie ; Daňková, Pavlína (advisor) ; Křepelová, Anna (referee)
Nanism is a kind of disorder characterized by an extremely small figure. It can be caused by hormonal, genetic or metabolic defects. This work, which is composed by study of materials in the form of article and publication mainly by foreign authors, is concerned with chosen types of nanism and their pathogenesis. All these types of this disease are caused by genetic defects in following genes: FGFR3, COMP, COL2A1, DTDST and PTH/PTHrP. Point mutations arising de novo are frequent cause of nanism and mostly are inherited autosomal- dominantly. It's a large group of disorders with different seriousness level: from light form like multiple epiphyseal dysplasia to lethal form such as thanatophoric dysplasia.
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Molecular genetic analysis of the causes of selected hereditary forms of colorectal polyposis
Florianová, Martina ; Kohoutová, Milada (advisor) ; Křepelová, Anna (referee) ; Vodičková, Ludmila (referee)
Colorectal cancer (CRC) is one of the most common cancers worldwide. Hereditary colorectal adenomatous polyposis syndromes are a predisposition to colorectal carcinoma development. The most common analyzed syndromes are familial adenomatous polyposis (FAP) that results from germline mutations in the APC gene and MUTYH - associated polyposis (MAP) caused by germline mutations in the MUTYH gene. The aim of this study was to clarify genetics causes of colorectal polyposis in a set of probands without the germline mutation in the APC gene. Within studyʼs scope the presence of large deletion in APC gene was tested, there was looked for germline mutations in MUTYH gene, alternatively germline mutations in MSH6 gene by probands with monoallelic MUTYH mutation, item there was tested an effect of detected APC variants on gene expression. Screening for large deletions was performed by multiplex ligation dependent probe amplification (MLPA). A set of 120 APC-negative probands was examined for the presence of germline MUTYH mutations by denaturing high performance liquid chromatography (dHPLC). Subsequently a set of 145 APC-negative probands was screened only for germline MUTYH mutation in exon 7 and 13 by high resolution melting (HRM) analysis. Analysis of the effect on expression was tested by ten APC...
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Microsatellite instability in hereditary nonpolyposis colorectal cancer patients
Sekowská, Martina ; Křepelová, Anna (advisor) ; Mareš, Jaroslav (referee) ; Kleibl, Zdeněk (referee)
Detection of microsatellite instability (MSI) is the standard part of mutational analysis in hereditary nonpolyposis colorectal cancers (HNPCC). Characteristic phenotypic feature of MSI indicates loss of mismatch repair (MMR) in tumor cells. We studied MSI in 205 tumors from 152 patients with HNPCC. Of these, 37 patients fulfilled Amsterdam criteria, 72 patients were familial and 43 were sporadic cases. We used methods of fragmentation analysis on polyacrylamide gel and/or with fluorescent labelled primers (ABI Prism 310 Genetic Analyzer). Three mononucleotide (BAT-RII, BAT-25, BAT-26) and five dinucleotide (D2S123, D3S1029, D5S346, D17S250, D18S58) repeat loci were analysed. We detected 75 tumors with high degree of MSI (MSI-H), 12 tumors with low degree of MSI (MSI-L) and 118 tumors with stable microsatellites (MSS). In 44 of these, loss of heterozygozity (LOH) was found. In 30 patients with MSI-H tumors a mutation in one of mismatch repair genes was detected. Microsatellite analysis was positively correlated with immunohistochemical detection of MLH1 and MSH2 proteins.
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