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Exploration of oncogenomic factors for prognostication and prevention of breast, ovarian, and colorectal cancers
Holý, Petr ; Souček, Pavel (advisor) ; Bouchal, Pavel (referee) ; Šulc, Miroslav (referee)
(Abstract) Cancer is now the leading cause of death in economically developer countries, with epidemiological indicators rising steadily on a global scale. This is mainly a result of socio- economic and demographic developments, particularly ageing populations or changes in lifestyle in some populations. Meanwhile, as absolute incidence and mortality rates are rising, the prevalence of cancer is also increasing, representing a heavy social and economic burden. Cancer research has received a great deal of attention from the scientific community, with molecular genetics in particular making the greatest recent progress. Thanks to modern methods of genome analysis, so-called genomics and other 'omics' disciplines, many biomarkers have been discovered, leading to better diagnosis, prognosis and more effective treatment with reduced incidence of adverse effects. However, there is still a long way to go in order to make the idea of personalised oncology, i. e., a precise therapeutic approach tailored to the individual patient, a reality. This paper examines three types of solid tumours. Firstly, breast cancer, which has the highest incidence worldwide in women, even overall. The next is colorectal cancer, which is the second and third most common cancer in women and men, respectively, and more common in...
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Identification of Organisms Based on Analysis of Nucleotide Density Vectors
Maděránková, Denisa ; Babula, Petr (referee) ; Schwarz, Daniel (referee) ; Provazník, Ivo (advisor)
Most methods for analysis of genomic data work with symbolic sequences. Numerically represented genomic sequences can be analyzed by signal processing methods. A new method of numerical representation of DNA sequences, nucleotide density vectors, is proposed in this thesis. Usability of this method for purposes of molecular species identification is tested on DNA barcoding sequences. DNA barcoding is modern and popular methodology based on comparison of short mitochondrial DNA sequences. Beside species identification by proposed method based on nucleotide density vectors, higher taxa rank identification (e.g. families) was also tested. Furthermore, dendrograms were constructed from standardly used evolutionary distances and distances between nucleotide density vectors and the dendrograms were compared.
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Comparative Analysis of Silk Proteins and Discovery of Novel Sericin Gene in Lepidopteran Moths
WU, Bulah Chia-Hsiang
This thesis focuses on the silk components of the Mediterranean moth, Ephestia kuehniella, and the discovery of a novel silk gene, P150/ser6, in the silkworm, Bombyx mori. We analyzed and described the cocoon silk components in both species. In the first publication, we combined transcriptomic, genomic, and proteomic approaches to identify silk proteins in E. kuehniella. In the second publication, we described the discovery of gene P150/sericin6 in B. mori based on microsynteny analysis.
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Transcriptomics and developmental plasticity of sensory systems in fishes
Lupše, Nik ; Musilová, Zuzana (advisor) ; Reichard, Martin (referee) ; Barluenga, Marta (referee)
Organisms depend on sensory input to survive and thrive. Vision is a key sensory system to many vertebrates, including ray-finned fishes (Actinopterygii). Sight is enabled by the retina composed of cone and rod photoreceptors, each characterised by its own set of opsin proteins that together with the chromophore form the photo-sensitive pigment. Vision is energetically very costly and so it is often adapted to specific photic conditions to best match available wavelengths of light. This Ph.D. thesis focuses on the evolution and development of opsin gene expression in ray-finned fishes. It mainly aims to explore how ontogenetic differences of visual capabilities across the fish phylogeny relate to ecological conditions. In some species, ecological shifts between developmental stages can affect their physiology, including vision. In this thesis I focused on the molecular differences of the visual system between developmental stages, mostly focusing on larvae and adults. The first chapter of the thesis focuses on developmental changes in deep-sea fishes, a unique group of organisms that has evolved unconventional adaptations to maximise photon capture in an otherwise photon- depleted environment. Most deep-sea fishes start their lives in the shallow, sun-lit, predator and food abundant epipelagic...
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Speciation genomics in nightingales
Mořkovský, Libor ; Reifová, Radka (advisor) ; Macholán, Miloš (referee) ; Piálek, Lubomír (referee)
Speciationisusuallyaslowprocessoccurringoverthousandstomillionsofyears.Thismakes speciation research difficult because no direct observation or manipulation is possible. At best, we can gain some insight by inferring the population history and structure in very fine detail by investigating genetic markers in multiple individuals of the nascent species. Today, speciationresearchisinanunprecedentedpositionthankstotheadventofhigh-throughput sequencingmethods,whichmakeiteasier and cheaper than ever before to evaluate multiple markers in many individuals. Speciation is not a straightforward process that happens in the same way every time, but rather a phenomenon occurring when genetic and ecological circumstancesactinginsymphonyultimatelyleadtoreproductiveisolationoftwosubpopula- tions. This is why it is important to study multiple model systems to understand the general principles behind speciation. We worked with two species of nightingales (Luscinia luscinia andL.megarhynchos)thatdivergedapproximately1.8Mya,likelyduetoglacialfluctuations in Europe. Our main goal was to use these new high-throughput sequencing methods to (1) detect interspecific hybrids between the species, (2) estimate levels of interspecific gene flow,(3)findareasofthenightingalegenomethatunderliereproductiveisolationand,finally, (4)...
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Surface phenotype of human carcinoma cancer stem cells (CSC)
Bočková, Marie ; Drbal, Karel (advisor) ; Čermák, Vladimír (referee)
Tumor is composed of a heterogenous mass of cells. Similar to normal healthy organs and tissues, these can be divided into individual cellular subpopulations according to morphology, function and expression patterns. A subpopulation of cells that are able to give rise to all of these cellular lineages is referred to as cancer stem cells (CSC). CSCs have the capabilities of normal stem cells such as the self-renewal and the ability to give rise to a heterogenous population of differentiated cells. Usually, this is the most resistant subpopulation within a tumor, highly non-responsive to therapy. Doing so, they are the cause of residual disease. Characterisation of CSC markers of individual tumor types is beneficial since it enables higher therapy efficacy via targeting this cell population. The -omics approaches to characterisation of the surface proteome bring a broader view into the field when searching for a unique gene signature of specific cancer stem cell types. It has been found that these cells can be identified based on the high expression levels of CD44, CD90 and CD49f. Among other markers, CD47 is an important marker for its immunosuppressive function.
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Genomic approach in speciation studies
Habalová, Kateřina ; Hulva, Pavel (advisor) ; Mikulíček, Peter (referee)
Speciation, adaptation and hybridization are three concepts, each one referring to different process but having a common evolutionary context. Maternal line splits into two sister lines or only one line cleaves from maternal one during speciation. However it leads to formation of new species. Adaptation and hybridization can lead to formation of new species as well. New species arise by adapting to new conditions during adaptation. Within hybridization it is a desecendant of two different lines mating amongst themselves. Most of this thesis is being addressed to these issues, the lesser part is addressed to specific examples. The chapter about next-generation sequencing methods is also included, as these methods have been used more frequently recently. Key words: speciation, adaptation, hybridization, genomics, next-generation sequencing
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Implemenation of the RAD sequencing methods to the population genetic studies of hedgehogs from the genus Erinaceus
Loudová, Miroslava ; Černá Bolfíková, Barbora (advisor) ; Choleva, Lukáš (referee)
Hedgehogs from the genus Erinaceus are an important model organism for studying the postglacial recolonisation of Europe and the processes that take place in the secondary contact zones of their areas of distribution. In this study, five individuals of white-breasted hedgehog (Erinaceus roumanicus), four individuals of western hedgehog (Erinaceus europaeus) and one estimated hybrid were analysed. Geographical distribution of individuals used in the study covers the region of the Central Europe, however in the further research expansion of analsysed individuals will be needed and the whole Palearct should be sampled. The main goal was to implement novel methods in research of hedgehogs, which will enable to map the population-genomic structure of the genus Erinaceus in western Palearct. The method RADSeq (Restriction site associated DNA sequencing) enables to obtain polymorphic markers, e.g., SNPs which we used (Single Nucleotide Polymorphisms) across the genome. In this work it was analyzed 16382 SNPs. Using the binary data which indicates the presence and absence of SNPs for each species, hypotheses raised under classical analyzes of genetic markers from previous studies have not been fully confirmed. In further research it will be necessary to verify possible occurrence of biases connected with...
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Speciation genomics in nightingales
Mořkovský, Libor
Speciationisusuallyaslowprocessoccurringoverthousandstomillionsofyears.Thismakes speciation research difficult because no direct observation or manipulation is possible. At best, we can gain some insight by inferring the population history and structure in very fine detail by investigating genetic markers in multiple individuals of the nascent species. Today, speciationresearchisinanunprecedentedpositionthankstotheadventofhigh-throughput sequencingmethods,whichmakeiteasier and cheaper than ever before to evaluate multiple markers in many individuals. Speciation is not a straightforward process that happens in the same way every time, but rather a phenomenon occurring when genetic and ecological circumstancesactinginsymphonyultimatelyleadtoreproductiveisolationoftwosubpopula- tions. This is why it is important to study multiple model systems to understand the general principles behind speciation. We worked with two species of nightingales (Luscinia luscinia andL.megarhynchos)thatdivergedapproximately1.8Mya,likelyduetoglacialfluctuations in Europe. Our main goal was to use these new high-throughput sequencing methods to (1) detect interspecific hybrids between the species, (2) estimate levels of interspecific gene flow,(3)findareasofthenightingalegenomethatunderliereproductiveisolationand,finally, (4)...
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