|
|
Determination of mutation spectrum and frequency representation of variants in genes involved in Melanocortin Receptor Type 4 Signaling Cascade (MC4R)
Toman, Izabela ; Včelák, Josef (advisor) ; Aldhoon Hainerová, Irena (referee)
This master's thesis is focused on determination of mutation spectrum and frequency representation of variants in genes involved in Melanocortin Receptor Type 4 Signaling Cascade. Mutation in genes connected to MC4R signalisation cascade may induce so called monogenic type of obesity, which is characterised not only by mutation in single gene but also by an early onset severe obesity and hyperphagia. Due to new means of medications being introduced its especially important to ascertain the frequency of mutations in Czech children and adolescent population. Theoretic part of the thesis is devoted to description of energy homestasis and leptin- melanocortin pathway. Physiology of hunger and satiety and the most common causes of obesity and monogenic obesity are also included. There is also mention of population differences in genetical predisposition for monogenic obesity namely in genes MC4R, POMC, SIM1 and BDNF which were the focal points of this thesis. In practical part, genetical analysis of 1910 samples from Czech children and adolescent population was implemented. We identified twelve different, likely pathogenic causal variants via next generation sequencing. More precisely eight different MC4R variants, 2 POMC variants and 2 SIM1 variants. In those, two novel variants were found c.346 C> T...
|
|
|
The genetic background of obesity and its treatment with bariatric surgery
Lischková, Olga
Obesity is a frequent metabolic disease that causes many other health and socioeconomic complications. Obesity arises due to excessive energy intake and decrease in energy expenditure, which is a conseqence of contemporary lifestyle. Moreover, obesity has a strong genetic component. Common obesity is polygenic, multifactorial disease, in which individual genes interact with each other and with environmental factors. Genome-wide association studies, conducted between 2006-09, led to the discovery of dozens of gene loci that predispose individuals to obesity. The strongest signals were registered for polymorphisms in FTO (fat mass and obesity-associated) and near a gene MC4R (melanocortin 4 receptor). However, the contributions of these variations on the phenotype of obesity are very small, therefore, it is necessary to validate the results of such robust studies. It is very important to uncover the effects of genetic variants for understanding the molecular mechanisms of energy metabolism. The studies presented in this thesis refer about the impact of polymorphisms in selected genes on anthropometric and metabolic parameters of the patients of the Institute of Endocrinology and of healthy volunteers who underwent functional tests. Our cohort includes a representative sample of Czech children (COPAT...
|
|
|
Variabilita genů IGFBP2 a MC4R ve vztahu ke kvalitě masa prasat
Steinerová, Michala
The aim of this diploma thesis was association analysis of single nucleotide polymorphism of IGFBP-2 and MC4R genes in a selected group of Czech Large White pigs with indicators of pork quality. The surveyed traits were pH value, color of meat, electrical conductivity, drip loss, contents of intramuscular fat and fatty acids. The polymorphisms were detected by the PCR and RFLP procedures. The allele and genotype frequencies were calculated and results were statistically evaluated using SAS program. In the case of the IGFBP-2 gene was discovered, that the observed set of animals is marked out by the higher percentage of allele B (99,5 %), the relative frequency of the BB genotype was 99 %, AB 1 % and genotype AA has not been found. For this reason, an association analysis could not be performed. The MC4R gene showed a higher frequency of the G allele (74.52%), with the relative frequency of AA genotypes being 2.88%, AG 45.19% and GG 51.92%. On the basis of the association analysis, statistically significant differences were found in the content of the linoleic acid at significance level of P ≤ 0,05 between genotypes AG×GG and to the drip loss where was the difference between the genotypes AA×GG. No statistically significant differences were found for other meat quality indicators, not even value close to significant difference (P ≤ 0,1).
|
|
|
Monogenic causes of obesity
Toman, Izabela ; Včelák, Josef (advisor) ; Vaňková, Markéta (referee)
In recent years the prevalence of obesity has significantly increased, pursued by multiplication of patients with type 2 diabetes, cardiological problems and premature death. Between the most dangerous forms of obesity belongs its monogenic type as it is a disease caused by single causal mutation with typical phenotype of severe obesity and hyperphagia. The aspiration of this thesis is to summarise the most important genes, mutation of which may cause monogenic type of obesity. The first chapters outline general genetic causes of obesity and importance of Leptin-melanocortin pathway in terms of its role in energy homeostasis. Subsequent sections identify genes involved in monogenic obesity, e.g. MC4R, LEP, LEPR, SIM1 and BDNF. Finally, the thesis summarizes possible new treatments, including new drug "Setmelanotide". Key words: Genetics, Obesity, Monogenic obesity, Leptin-Melanocortin pathway, MC4R, Setmelanotide
|
|
|
The genetic background of obesity and its treatment with bariatric surgery
Lischková, Olga ; Bendlová, Běla (advisor) ; Šeda, Ondřej (referee) ; Mráz, Miloš (referee)
Obesity is a frequent metabolic disease that causes many other health and socioeconomic complications. Obesity arises due to excessive energy intake and decrease in energy expenditure, which is a conseqence of contemporary lifestyle. Moreover, obesity has a strong genetic component. Common obesity is polygenic, multifactorial disease, in which individual genes interact with each other and with environmental factors. Genome-wide association studies, conducted between 2006-09, led to the discovery of dozens of gene loci that predispose individuals to obesity. The strongest signals were registered for polymorphisms in FTO (fat mass and obesity-associated) and near a gene MC4R (melanocortin 4 receptor). However, the contributions of these variations on the phenotype of obesity are very small, therefore, it is necessary to validate the results of such robust studies. It is very important to uncover the effects of genetic variants for understanding the molecular mechanisms of energy metabolism. The studies presented in this thesis refer about the impact of polymorphisms in selected genes on anthropometric and metabolic parameters of the patients of the Institute of Endocrinology and of healthy volunteers who underwent functional tests. Our cohort includes a representative sample of Czech children (COPAT...
|
|
|
The genetic background of obesity and its treatment with bariatric surgery
Lischková, Olga
Obesity is a frequent metabolic disease that causes many other health and socioeconomic complications. Obesity arises due to excessive energy intake and decrease in energy expenditure, which is a conseqence of contemporary lifestyle. Moreover, obesity has a strong genetic component. Common obesity is polygenic, multifactorial disease, in which individual genes interact with each other and with environmental factors. Genome-wide association studies, conducted between 2006-09, led to the discovery of dozens of gene loci that predispose individuals to obesity. The strongest signals were registered for polymorphisms in FTO (fat mass and obesity-associated) and near a gene MC4R (melanocortin 4 receptor). However, the contributions of these variations on the phenotype of obesity are very small, therefore, it is necessary to validate the results of such robust studies. It is very important to uncover the effects of genetic variants for understanding the molecular mechanisms of energy metabolism. The studies presented in this thesis refer about the impact of polymorphisms in selected genes on anthropometric and metabolic parameters of the patients of the Institute of Endocrinology and of healthy volunteers who underwent functional tests. Our cohort includes a representative sample of Czech children (COPAT...
|
guest ::
