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Functional genomic and pharmacogenomic analysis of metabolic syndrome aspects
Krupková, Michaela ; Šeda, Ondřej (advisor) ; Haluzík, Martin (referee) ; Polák, Jan (referee)
Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...
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Bacterial REP elements: origins, variability and application.
Nunvář, Jaroslav
4 ABSTRACT (English) This thesis is based on three published research papers studying bacterial REP (repetitive extragenic palindrome) elements. REP elements are one of the best-characterized groups of bacterial DNA repeats, distributed mostly in gammaproteobacteria, including enterobacteria. They are present in noncoding parts of host genomes, usually occurring in hundreds of copies. REPs are typically aggregated in higher order repeats. In the Gram-negative model Escherichia coli, interactions of several proteins important for cell's physiology with REPs were described, indicating significant role for these elements for host cells. The first work (Nunvar et al. 2010) presents the discovery of a protein class, related to IS200/IS605 transposases. These proteins, termed RAYTs (REP-associated tyrosine transposases), contain characteristic motifs in their amino acid sequences, which are absent in canonical IS200/IS605 transposases. Another attribute of RAYTs is the arrangement of their encoding genes. These are single copy genes, always flanked at both termini by at least two REPs in inverted orientation. Based on the similarity between the REP-rayt-REP unit and insertion sequences of the IS200/IS605 family, between RAYTs and tyrosine transposases and between REPs and subterminal sequences of the IS200/IS605...
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Bacterial REP elements: origins, variability and application.
Nunvář, Jaroslav ; Lichá, Irena (advisor) ; Pačes, Jan (referee) ; Melter, Oto (referee)
4 ABSTRACT (English) This thesis is based on three published research papers studying bacterial REP (repetitive extragenic palindrome) elements. REP elements are one of the best-characterized groups of bacterial DNA repeats, distributed mostly in gammaproteobacteria, including enterobacteria. They are present in noncoding parts of host genomes, usually occurring in hundreds of copies. REPs are typically aggregated in higher order repeats. In the Gram-negative model Escherichia coli, interactions of several proteins important for cell's physiology with REPs were described, indicating significant role for these elements for host cells. The first work (Nunvar et al. 2010) presents the discovery of a protein class, related to IS200/IS605 transposases. These proteins, termed RAYTs (REP-associated tyrosine transposases), contain characteristic motifs in their amino acid sequences, which are absent in canonical IS200/IS605 transposases. Another attribute of RAYTs is the arrangement of their encoding genes. These are single copy genes, always flanked at both termini by at least two REPs in inverted orientation. Based on the similarity between the REP-rayt-REP unit and insertion sequences of the IS200/IS605 family, between RAYTs and tyrosine transposases and between REPs and subterminal sequences of the IS200/IS605...
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Contrasting patterns of karyotype and sex chromosome evolution in Lepidoptera
ŠÍCHOVÁ, Jindra
It is known that chromosomal rearrangements play an important role in speciation by limiting gene flow within and between species. Furthermore, this effect may be enhanced by involvement of sex chromosomes that are known to undergo fast evolution compared to autosomes and play a special role in speciation due to their engagement in postzygotic reproductive isolation. The work presented in this study uses various molecular-genetic and cytogenetic techniques to describe karyotype and sex chromosome evolution of two groups of Lepidoptera, namely selected representatives of the family Tortricidae and Leptidea wood white butterflies of the family Pieridae. The acquired knowledge points to unexpected evolutionary dynamics of lepidopteran karyotypes including the presence of derived neo-sex chromosome systems that originated as a result of chromosomal rearrangements. We discuss the significance of these findings for radiation and subsequent speciation of both lepidopteran groups.
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Comparison of genomes by synteny block analysis
Pavel, Tomáš ; Škutková, Helena (referee) ; Maděránková, Denisa (advisor)
The theoretical part of this bachelor thesis is aimed at basics of genetics. Term of gene and mutation are introduced in this section. There are gene and chromosome mutations mentioned and described. Following section is devoted to comparative genomics and especially to synteny. There is described what the synteny actually is and how the synteny arises. The end of the theoretical part of this thesis is about the evolution and there are described ways of sorting permutation vectors. The practical part of this bachelor thesis includes description of developed software. Output of this software is a dot-plot which shows detected synteny blocks. Indexes of these blocks are listed in GUI. The second important output is number of permutation steps. This number determines evolutionary distance between two analysed DNA sequences. The very last section is aimed at analyse of synthetic and real DNA sequences.
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