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Trombophilic states during pregnancy
Košatová, Andrea ; Ehler, Edvard (advisor) ; Pavlasová, Lenka (referee)
The aim of this thesis is to summarize the available data concerning the influence of trombophilic states on the process of pregnancy and to present the results obtained by investigating the prevalence of congenital trombophilia in infertile women and its influence on the success rate of assisted reproduction. It is aimed at those interested in the problematics - be it professionals, medical students or women planning pregnancy or cannot get pregnant. The theoretical part draws data from literature written by leading Czech experts in the field and from scientific journals, included are also foreign sources. The practical part was executed with the kind permission of the PRONATAL s.r.o. centre for assisted reproduction. Key words: venous thromboembolism, trombophilia, trombophylaxis, gravidity, mutation, screening
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Clinical and genetic aspects of familial breast cancerFrequency of recurrent mutations in BRCA1 and BRCA2 genes in Czech republic and the role of NBN gene
Matějů, Martin ; Novotný, Jan (advisor) ; Konopásek, Bohuslav (referee) ; Vaňásek, Jaroslav (referee)
Summary: Background: An increased risk for development of hereditary breast cancer is associated with germline mutations in BRCA1/2 and the influence of NBN mutations is also supposed. The aim of this study is to specify the frequency of recurrent mutations in BRCA1/2 in unselected breast cancer patients and the frequency of most common pathogenic mutations in NBN in Czech republic, to assess current criteria for genetic testing and to consider the addition of NBN to the tested genes. Methods: Screening for recurrent mutations 5382insC and 300T>G in BRCA1 was performed by RFLP, screening for mutations in exon 11 of BRCA1 was performed by PTT, screening for mutations in a selected region of exon 11 of BRCA2 by DHPLC, and screening for mutations in exon 6 of NBN by HRMA. All the mutations were confirmed by direct sequencing. Results: In 679 unselected breast cancer patients 7 carriers of 5382insC, 3 of 300T>G, and 4 of other mutations in BRCA1 were identified. 2 locally prevalent mutations were found in BRCA2. In 730 controls only one 5382insC BRCA1 mutation was identified. Out of 5 NBN mutations found in 600 high-risk patients two were 657del5 and one R215W. A total of 8 NBN mutation carriers were identified among 703 breast cancer patients, 2 of them 657del5 carriers and three R215W carriers. In 915...
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The role of estrogen receptors in prognosis and therapy outcome of breast cancer
Kloudová, Alžběta ; Souček, Pavel (advisor) ; Dračínská, Helena (referee)
Estrogen receptors (ER) are members of nuclear receptor family, which mediate distinct physiological functions after binding a steroid ligand. Apart from that they play a role in many diseases including breast cancer. ER is among proteins routinely evaluated in clinical practice and on the basis of ER expression, patients are treated by endocrine therapy. There are different opinions of the role of ER in cancer cells, but in the future, detection of ER and treatment by ER- and ER-selective ligands could contribute to improvement of cancer therapy. Isoforms, mutations and posttranslational modifications of ER present other important factors, which can influence estrogen signalization and endocrine therapy efficiency and deciphering of their importance for cancer cells could bring better understanding of ER signalization and improvement of the therapy.
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Changes of the gene concept in the first half of the 20th century
Hájková, Jana ; Neubauer, Zdeněk (advisor) ; Vondrejs, Vladimír (referee) ; Šimůnek, Michal (referee)
This dissertation shows various concepts of the term gene that have appeared since the birth of genetics in 1900 up to the first half of the 50s. It focuses especially on the 40s and the beginning of the 50s. Scientific papers from that period were the main source of information. The author tried to capture not only generally accepted notions about genes and genic action but also those that had not pushed through in those days, nevertheless, that had offered a non- standard point of view which could have later become inspirative for molecular genetics. The work documents searching for links between genes and enzymes or ideas of potential divisibility of the gene. The dissertation assigns a very important role to those phenomena that emphasized the significance of the gene order or the order of genic parts. In Goldschmidt's interpretation of pseudoallelism the author sees the thought that the essence of a gene is its position and considers this the beginnings of "digital" thinking about the gene. The dissertation pays attention to "analogue" thinking about the gene, as well. This thinking took account of molecular shaping and represented a blind alley for the early molecular genetics. The work confirms to a certain extent the Kuhnian vision of the development of scientific disciplines. It finds the...
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The possibilities of genetic testing for mutation and polymorphisms in connection with cardiovascular diseases.
ČALOUNOVÁ, Lucie
Cardiovascular diseases (CVD) belong to the most current issues nowadays and they are the most frequent death reasons in the developed countries. Atherosclerosis and thrombosis, which might be genetically determined rank among the main causes of the inception. Knowledge of genetic predispositions might be helpful for patients to minimize the risk of CVD. Other prevention such as healthy lifestyle and restriction or better to say complete elimination of high risk factors, e.g. smoking is very important though. The goal of this bachelor work is practical mastery of reverse hybridization on strips to detect the mutations and polymorphisms, which are related to cardiovascular diseases and prepare the research into this issue. In the theoretical part, I apply with a description of mutations and polymorphisms closely related to cardiovascular diseases, which might be identified with the help of kit CVD Strip Assay within one experiment. Afterwards I pay attention to the description of alternative analytic methods recognizing above mentioned selective mutations and polymorphisms. I deal with my own results obtained in the genetic laboratory GENLABS ltd. These are the FV Leiden, FV R2 haplotype, prothrombin, FXIII, -fibrinogen, PAI-1, HPA-1, MTHFR 677, MTHFR 1298, ACE, Apo B, Apo E. I used the method of reverse hybridization on strips to identify the mutations and polymorphs. The patients' samples from the GENLABS laboratory were used to this research.
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Gene mutations affecting the development of human testes
Macháčová, Simona ; Šebková, Nataša (advisor) ; Ševčíková Jonáková, Jana (referee)
Development of mammalian sex organs is remarkable process. Both ovaries and testes rise from the same precursor but then differentiate into morphologically and functionally different structure. The determining factors that decide the fate of undifferentiated structures are not just the genes themselves but also the timing of transcription regulatory genes and specific amount of their products. Development of male and female gonads manages a large set of regulatory genes that interact with each other. Together it forms the gene regulatory network. Crucial role in male sex differentiation plays an SRY gene which regulates the time and quantity of the other factors expression. Even slight errors (mutations) in genes sequences of regulatory genes could change their expression. This leads to disruption of the development of sex organs or even death of the whole organism. Naturally occurring mutations and their phenotype in humans are suitable for studies of gene sex regulatory factors. Thanks to these studies we are able to detect the cause of many birth defects what is a first step toward their eventual treatment.
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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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Genetic basis of phenotypic variability in domesticated animals
Majerová, Veronika ; Komárek, Stanislav (referee) ; Reifová, Radka (advisor)
Understanding the mechanisms responsible for the origin of morphological variability among different species of animals represents an important goal in evolutionary biology. Origin and changes of the phenotypic variability during the evolution is possible to study in domesticated animals. The domesticated species of animals represent a brilliant model for studying the molecular mechanisms responsible for origin of new phenotypes due to enormous morphological variability of different domesticated breeds, effortless breeding in captivity and frequent knowledge of the genomic sequence. The aim of this bachelor work is to summarize actual findings about concrete mutations which are responsible for the origination of the new morphological characters in the domesticated animals. These findings can help us to clarify how the evolution functions on the molecular level.
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Application of the method RFLP PCR , PCR ARMS and reverse hybridization for detecting the most common thrombophilic mutations in the Czech population
MATĚJKOVÁ, Markéta
Recently the term thrombophilia is becoming a current topic. It is an increased precondition for the creation of tromboses and the following complications as the result of increased blood coagulation which could be very serious or even fatal. A timely diagnosis of thrombophilia mutations helps patients to avoid many critical situations (e.g. in case of operations, pregnancy etc.). In these days there are at least 30 genetic laboratories in the Czech Republic which research thrombophilia mutations. Unfortunately this medical examination is covered by insurance companies just in case of indicated symptoms which are under strict criteria. If someone is interested in a medical examination and a doctor does not indicate him with the symptoms, they are forced to pay the examination on their own. There are a few insurance companies which contribute with some amount for these examinations as a part of their preventive programmes (e.g. Česká průmyslová zdravotní pojišťovna, Zdravotní pojišťovna ministerstva vnitra ČR or Zdravotní pojišťovnu Revírní bratrská pokladna). The aim of my bachelor thesis was a practical mastery RFLP-PCR method, PCR ARMS method and a reverse hybridization on strips to detect the most common mutations of thrombophilia in the population of the Czech Republic and deviloving on the issue. In the theoretical part, I focus on a description of the most important thrombophilic mutations in the Czech population and their risks. I also describe particular genetic methods by which each of thrombophilia mutations is being examined in genetic laboratories. My own results of the examination of four major thrombophilia mutations and polymorphs are shown in the practical part. These are the Leiden mutation, prothrombin mutation, MTHFR 1298 and MTHFR 677 polymorphs. For my examinations I used these genetic methods: RFLP-PCR method, PCR ARMS method, reverse hybridization on strips. I made all these methods in the genetic laboratory Genlabs in České Budějovice. For the examinations I used DNA samples of my family.
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Dědičná metabolická onemocnění u psů
ŠOLÁ, Jitka
The thesis deals with the most important inherited metabolic diseases in dogs. The thesis summarizes basic findings about eight inherited metabolic diseases, including pyruvate dehydrogenase phosphatase 1 deficiency (PDP1), phosphofructokinase deficiency (PFKD), pyruvate kinase deficiency (PK Def.), cystinuria, fucosidosis, L-2-HGA aciduria, GM1-gangliosidosis and copper toxicosis (CT). Essential characteristic, clinical view, genetic background and possibilities of current diagnostics and treatment are stated for each disease. Most of these disorders have the same genetic background and clinical symptoms like in the humans, which is why dogs serve as animal models for the development of the therapeutic methods for the human population.
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