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Bioinformatic analysis of single nucleotide polymorphisms in the 1000 Genomes Project database
Parobková, Viktória ; Roy, Sudeep (referee) ; Provazník, Ivo (advisor)
Sekvenovanie celého ľudského genómu a nájdenie jeho variácii bolo výzvou počas mnohých rokov. Znalosť všetkých genetických variácií je pozoruhodne prospešná pri výskume chorôb. Táto práca je zameraná na genetické variácie človeka a ich dva hlavné výskumné projekty, The HapMap Project a The 1000 Genomes Project, ktoré pomohli v analýze chorôb. Prvá časť práce je venovaná teoretickému popisu projektov. V nasledujúcej časti práce sú popísané štruktúry databáz u oboch projektov a taktiež je predstavený online nástroj umožňujúci prehľadávanie a sťahovanie ich dát. Následne je prevedená štatistická, populačná a bioinformatická analýza štrukturálnych variácií produkovaných 3 fázou 1000 Genomes projektu.
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Population Structure and History of the Sahel From the Point of View of Alcohol Metabolism
Jurišová, Lívia ; Černý, Viktor (advisor) ; Macholán, Miloš (referee)
The Sahel is the northernmost part of sub-Saharan Africa. The Sahel is inhabited by a complex mixture of people, who differ in their ethnic background, language affiliation and lifestyle. The most important and most studied gene of ethanol metabolism, ADH1B, has been understudied in the Sahel region, mainly due to the low frequency of the variant rs1229984-T, which accelerates the first step of alcohol metabolism. Due to its non- African origin, the variant rs1229984-T represents a suitable marker for population history study. The eastern Sahel is where immigrants from Arabia have been settling and mating with African populations since the 7th century CE. To study population structure and history from the point of view of alcohol meta- bolism, we have used already known genotype data from fourteen Sahelian populations, which inhabit mainly the eastern part of the region. Due to the absence of the critical locus rs1229984 in the genotyping array, the samples have been subjected to sequen- cing. Combined data from the microarray and the sequencing constituted 26 loci of the ADH1B gene and its close periphery, which came from 318 samples. Genotypic data needed to be converted into their haplotypic form by a phasing prog- ram. To choose the more appropriate phasing program, the data have been arranged...
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Rapidly mutating Y-STRs analysis as a tool for forensic investigations, genetic genealogical applications and molecular anthropology
Jakub, David ; Šimková, Halina (advisor) ; Doubková, Klára (referee)
Compared to standard Y-STR markers commonly used in forensics and bioarchaeology, rapidly mutating Y-STR markers (RM Y-STR) have a significantly higher haplotype diversity and lineage resolution abilities in world populations. They form a novelty in these fields. This paper will attempt to clarify their origin, function, and efficacy in forensic genetics, genealogy, and molecular anthropology by looking at the Y chromosome and its characteristics that allow its use in the mapping of populations, individual male lineages, and identifying male perpetrators of sexual violence. By looking at other polymorphisms of the Y chromosome, especially Y-SNP markers, we can see in which studies each type is used most effectively. In the end, it will be clarified whether the use of RM Y-STR markers is beneficial to each field, whether they make standard Y-STR markers redundant, or whether they are themselves of no substantial use in comparison.
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Evolution of PTC bitter taste receptors in West Africa
Holoubková, Tereza ; Černý, Viktor (advisor) ; Macholán, Miloš (referee)
The aim of this thesis is to determine whether the TASR38 gene is under selection pressure in West Africa and if its diversity varies within populations practicing different modes of subsistence. It further focuses on polymorphisms occurring in the gene and their association with sensitivity to the bitter tasting compound PTC. The thesis analyses 147 samples of saliva from three Mauritanian populations in order to sequence the DNA of the TAS2R38 gene exon. Ten polymorphic sites conditioning 16 haplotypes were observed in TAS2R38 gene. Mutations in amino acid positions 49, 262 and 296 occurred in all three populations; all eight possible haplotypes were observed. 94 % of them constitutes major PAV and AVI haplotypes and AAI haplotype, all of which were detected in each of the three populations. Additionally, 14 genotypes were identified in our sample; the most common being those created by a combination of the three haplotypes. Kruskal-Wallis test showed that TAS2R38 genotypes are strong predictors of PTC response in the examined African populations. PAV haplotype is associated with sensitivity to PTC (taster haplotype); conversely, AVI is a nontaster haplotype. At the same time, it was confirmed that PAV is an ancestral haplotype evolutionary closest to the chimpanzee TAS2R38 gene and it probably...
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Determination of mtDNA sequence variation in czech population for the usage in forensic genetics.
Řadová, Marie ; Coufalová, Pavla (advisor) ; Vaněk, Daniel (referee)
In forensic research and practice is used an analysis of nuclear DNA commonly. However, in some cases we can use only mitochondrial DNA. The mtDNA is maternally inherited and it is located in the each cell approximately in 500 copies. Barring mutation in special noncoding segments, the mtDNA sequence of siblings and all maternal relatives is identical. This unique haplotyp can be helpful in forensic cases, such as analyzing the remains of a missing person, where known maternal relatives can provide reference samples for direct comparison to the questioned mtDNA type. MtDNA is also very resistant to the external influences, so in the cases where the amount of extracted DNA is very small or degraded it is more likely that a DNA typing result can be obtained by typing mtDNA than by typing polymorphic markers found in nuclear DNA. If we want to have a certain probability to exclude or confirm the match of two samples, classify suspect or missing person into a population, we need some enough wide comparison by the population databases. Then we can study the frequencies of different haplotypes in particular population. The aim of this thesis is summery of history of DNA analysis, mtDNA sequencing and comparison of data available in published databases in the world and mainly in the Czech Republic. There is also...
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Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease
Václavíková, Eliška ; Bendlová, Běla (advisor) ; Dvořáková, Lenka (referee) ; Stárka, Luboslav (referee)
Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease Abstract Medullary thyroid carcinoma (MTC) and Hirschsprung's disease (HSCR) are classified as simple neurocristopathies, i.e. diseases linked to neural crest-derived cells. MTC is derived from parafollicular cells of the thyroid and HSCR is characterized by absence of enteric ganglia in the gastrointestinal tract. The RET proto-oncogene is only expressed in neural crest-derived cells, including parafollicular cells and enteric neurons. The RET encodes a transmembrane tyrosinekinase receptor that plays an important role during proliferation, differentiation and cell survival, and activates many signaling pathways. If the strictly regulated activation fails, e.g. due to mutations in the specific gene locations, the RET becomes a highly effective oncogene. Activating germline mutations in the RET proto- oncogene lead to hereditary forms of MTC, whereas sporadic forms of MTC are caused by somatic mutations in the tumor tissue. On the contrary, inactivating mutations induce migration failure of ganglion cell precursors during the development of enteric nervous system and result in the development of HSCR. In rare cases, the coexistence of both diseases is caused by mutations with a dual gain-of-function and loss-of-function character....
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Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease
Václavíková, Eliška
Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease Abstract Medullary thyroid carcinoma (MTC) and Hirschsprung's disease (HSCR) are classified as simple neurocristopathies, i.e. diseases linked to neural crest-derived cells. MTC is derived from parafollicular cells of the thyroid and HSCR is characterized by absence of enteric ganglia in the gastrointestinal tract. The RET proto-oncogene is only expressed in neural crest-derived cells, including parafollicular cells and enteric neurons. The RET encodes a transmembrane tyrosinekinase receptor that plays an important role during proliferation, differentiation and cell survival, and activates many signaling pathways. If the strictly regulated activation fails, e.g. due to mutations in the specific gene locations, the RET becomes a highly effective oncogene. Activating germline mutations in the RET proto- oncogene lead to hereditary forms of MTC, whereas sporadic forms of MTC are caused by somatic mutations in the tumor tissue. On the contrary, inactivating mutations induce migration failure of ganglion cell precursors during the development of enteric nervous system and result in the development of HSCR. In rare cases, the coexistence of both diseases is caused by mutations with a dual gain-of-function and loss-of-function character....
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Molecular genetic analysis of patients with Usher syndrome
Průšová, Kateřina ; Ďuďáková, Ľubica (advisor) ; Kousal, Bohdan (referee)
The work focuses on molecular genetic testing of patients with Usher syndrome to confirm the diagnosis, to determine the causal cause of the disease and describe new mutations causing Usher syndrome in Czech patients. Usher syndrome is a clinically and genetically heterogeneous disease that is the most common cause of hereditary deafblindness. Based on responsible genes and disease onset is classified into three clinical subtypes. Given the fact that there is currently no specific treatment, there is a need to understand the pathophysiology of this disease and to broaden the spectrum of causal mutations. The theoretical part of the thesis deals with the anatomy of the eye, especially the structure of the retina. Attention is also paid to retinal diseases, such as the progressive loss of vision characteristic for retinitis pigmentosa (RP). RP may occur either as an isolated disorder or also affecting other organs, so-called syndromic RP. Classic syndromic RP includes Usher's syndrome, which the work mainly deals with. The theoretical part of the thesis describes mainly the mechanism of the disease, the functions of individual Usher proteins and the genes that encode these proteins. The haplotype analysis has been previously done for the most common mutations causing Usher's syndrome in Europe Based...
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Bioinformatic analysis of single nucleotide polymorphisms in the 1000 Genomes Project database
Parobková, Viktória ; Roy, Sudeep (referee) ; Provazník, Ivo (advisor)
Sekvenovanie celého ľudského genómu a nájdenie jeho variácii bolo výzvou počas mnohých rokov. Znalosť všetkých genetických variácií je pozoruhodne prospešná pri výskume chorôb. Táto práca je zameraná na genetické variácie človeka a ich dva hlavné výskumné projekty, The HapMap Project a The 1000 Genomes Project, ktoré pomohli v analýze chorôb. Prvá časť práce je venovaná teoretickému popisu projektov. V nasledujúcej časti práce sú popísané štruktúry databáz u oboch projektov a taktiež je predstavený online nástroj umožňujúci prehľadávanie a sťahovanie ich dát. Následne je prevedená štatistická, populačná a bioinformatická analýza štrukturálnych variácií produkovaných 3 fázou 1000 Genomes projektu.
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Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease
Václavíková, Eliška ; Bendlová, Běla (advisor) ; Dvořáková, Lenka (referee) ; Stárka, Luboslav (referee)
Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease Abstract Medullary thyroid carcinoma (MTC) and Hirschsprung's disease (HSCR) are classified as simple neurocristopathies, i.e. diseases linked to neural crest-derived cells. MTC is derived from parafollicular cells of the thyroid and HSCR is characterized by absence of enteric ganglia in the gastrointestinal tract. The RET proto-oncogene is only expressed in neural crest-derived cells, including parafollicular cells and enteric neurons. The RET encodes a transmembrane tyrosinekinase receptor that plays an important role during proliferation, differentiation and cell survival, and activates many signaling pathways. If the strictly regulated activation fails, e.g. due to mutations in the specific gene locations, the RET becomes a highly effective oncogene. Activating germline mutations in the RET proto- oncogene lead to hereditary forms of MTC, whereas sporadic forms of MTC are caused by somatic mutations in the tumor tissue. On the contrary, inactivating mutations induce migration failure of ganglion cell precursors during the development of enteric nervous system and result in the development of HSCR. In rare cases, the coexistence of both diseases is caused by mutations with a dual gain-of-function and loss-of-function character....
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