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Spinal muscular atrophy
Bohatá, Jana ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder which affects α-motor neurons in anterior horns of spinal cord resulting in progressive muscle weakness. The estimated incidence is 1:10 000 and carrier frequency 1:40-1:60. SMA is classified into four grades depending on the age of onset and its severity. Life expectancy differs according to grade of SMA, patients suffering from the most serious grades live about two years, milder could live to adulthood. This disorder is caused by mutation of the SMN1 gene which is located on the fifth chromosome. In the majority of cases the type of mutation is homozygous deletion in SMN1 gene. Keywords: Spinal muscular atrophy; neuromuscular disorder; alpha motor neurons; autosomal recessive disorder; SMN1; SMN2
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The SHOX gene and clinical consequences of its defects
Klugerová, Michaela ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
The SHOX gene ("Short Stature Homeobox-containing Gene") was identified during research of genotype-phenotype corelations in patiens with Turner Syndrome. Absence one alele of this gene was the cause of short stature in these girls. Shortly after, mutations in SHOX gene were identified in patients with Léri-Weill and Langer syndrom, thus in patients with growth failure and skeletal deformities. It is estimated that mutations in SHOX gene or mutations in SHOX regulatory regions affect one in thousand of new born children. Mutations in this gene are one of the most common genetic causation leading to growth failure phenotype. However, the exact role of SHOX gene in bone growth and development is still unknown, therefore it is importnant to study problems with SHOX gene and try to discover mechanism of SHOX protein activity on molecular levels.
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Immunological causes of female infertility
Bajerová, Kateřina ; Brynychová, Iva (advisor) ; Novák, Jan (referee)
Currently, up to 15 % of reproductive age couples struggle with infertility. Female infertility is the cause of conception issues in nearly 40 % of these cases. The origin of female infertility consists of wide range of causes and other factors. Immunological causes are certainly one of the most significant ones. In pathological conditions, defense mechanisms of female immune system can target alloantigens presented on sperm surface. Moreover, autoimmune response and antibody production can occur as well. Antibodies can target various parts of ovarian follicles and oocytes, phospholipids, nuclear antigens, enzymes etc. These antibodies can inhibit fertilization, maturation of oocytes and embryo, embryo implantation, and also recurrent miscarriages. The aim of this thesis is to summarize various causes of female infertility focusing on immunological pathologies. The thesis also describes functioning of immune mechanisms in the female reproductive tract and briefly touches on oogenesis and female hormonal cycle.
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Cryptic Rearrangements of Human Chromosomes Associated with Schizophrenia
Jurišová, Lívia ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Schizophrenia is a severe mental disorder with high heritability and complex genetics which interacts with environmental factors and leads to a wide range of symptoms. The emergence of modern cytogenetic and molecular genetic techniques has allowed uncovering one of the po- ssible causes - cryptic chromosomal rearrangements. The size of rearrangements, also known as microdeletions and microduplications, is under 3-5 Mb. Aberrations may affect multiple genes and their gene dosage. The research of cryptic rearrangements in association with schizophrenia began in 2008 with the identification of three pathogenic aberrations. Over time studies have identified more cryptic rearrangements and new studies supporting or not supporting their role in the disorder have been published. Research of the candidate genes and their possible interac- tions has also been conducted. It is hypothesized that schizophrenia is caused by pathologically changed brain connectivity, in which the changed gene dosage by cryptic rearrangements may play a role. The research is in its beginnings, and we can expect the identification of new rear- rangements. Further research may lead to a better understanding of the origin and symptoms of schizophrenia, and play a role in prenatal diagnostics and treatment. Key words: cryptic...
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The role of NETosis in pathogenesis of autoimmune diseases
Pošmurná, Eliška ; Brynychová, Iva (advisor) ; Šolc, Roman (referee)
Neutrophil granulocytes - white blood cells are very effective in fight against pathogens with fagocytosis, degranulation, or NETosis, which is special form of cell death. During NETosis are created neutrophil extracellular traps, which can trap and destroy microorganisms with antimicrobial granules. NETosis can be iniciated by activation of pro-inflammatory cytokines, lypopolysacharides or phorbomystatic acid. Activated neutrophils get to the site of inflammation, where decondensed chromatin, part of NETs, gets into extracellular space. DNA in extracellular space is strong alarmin for immune system as part of NETs. Increased NETs production or problem with their elimination can play role in patogenesis of some autoimmune diseases (eg. Systematic lupus erythematodes, associated vasculitis, rheumatoid arthritis, diabetes mellitus). NETs production or their components can affect diseases or degree of damage to the surrounding tissue. It also correlates with seriousness of disease (eg. Associoated vasculitis) and can have diagnostical potencial (eg. Asociated vaskuloitides, rheumatoid arthritis or diabetes mellitus type 1). Keywords: NETosis, NETs, neutrophils, autoimmune diseases, immune system
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Anthropological aspects of male infertility
Sakmárová, Františka ; Novák, Jan (advisor) ; Brynychová, Iva (referee)
Nowadays, more and more couples have had trouble with conceiving a child. Worldwide, around 15 % couples are affected by infertility, while men make up for 20-70 % of this problem. In last decades, the prevalence of the male infertility has been rising globally, with the sperm quality parametres becoming worse. From the view of male infertility etiology, it is rather difficult to pinpoint reasons of this trend. Besides sick individuals whose infertility is caused by genetic or congenital malfunctions or infections, the male infertility affects seemingly healthy individuals as well. The infertility of these objectively healthy (albeit infertile) individuals is from the etiological point of view said to be caused by environmental factors, worst of them being endocrine disruptors, and lifestyle factors, such as obesity, alcohol, smoking and stress. This thesis presents a complex view of male infertility problem, describing both its current state in epidemiology and its changes in time and space. Further on, the thesis is dedicated to the etiology of male infertility, including the lifestyle factors, where anthropology point of view is accentuated. Keywords: male infertility, reproduction, sperm, sperm parameters, causes of male infertility
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Immunological causes of male infertility
Stiborová, Martina ; Brynychová, Iva (advisor) ; Dostálová, Pavla (referee)
Infertility is defined as the inability to persuade a child after one year of regular unprotected contact, occurs in about 15% of partner couples. In addition to genetic, anatomical, hormonal and infectious causes, the importance of immunopathological mechanisms that contribute to infertility is 15%. The immune system is designed to protect the body's intrinsic stability and respond to so-called "dangerous" signals that can be induced by sperm as autoantigens for men and alloantigens for woman. A healthy individual has protective mechanisms in place to protect sperm from possible attack of the immune system. Failure of protective mechanisms and the natural immune system can result in antibodies against sperm. Antibodies against sperm proteins negatively affect sperm fertilization and are one of the main causes of infertility. This paper describes the possible occurrence of anti-sperm antibodies in both sexes. It also describes the development of sperm, immunological properties of the male and female sexual tract, and briefly summarizes the properties of anti-sperm antibodies and the treatment of immunological infertility. Key words: Reproduction, infertility, sperm cells, antisperm antibodies, autoimmunity
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Causes currently increased incidence of thyroid carcinomas
Škarková, Barbora ; Brynychová, Iva (advisor) ; Dvořáková, Šárka (referee)
The thyroid carcinoma incidence has currently multiplied and the largest increase was recorded for thyroid papillary carcinoma. The aim of this work is to discuss factors increasing the risk of thyroid carcinoma. The only confirmed risk of developing this form of carcinoma is ionizing radiation mostly in connection with nuclear attacks and nuclear power plants disasters. Other risk factors include iodine intake and the influence of nitrates, both of which act as separate risk factors and also as factors increasing the risk potential of ionizing radiation. Thyroid carcinoma occur 3 times more frequently in women, therefore the risk factors specific for females, such as estrogens, assisted reproduction methods, pregnancy and hysterectomy, are also discussed. Hypothyroidism and Hashimoto's thyroiditis have a significant association with thyroid carcinomas while controversial factors are risky elements of lifestyle and nutrition (eg smoking, cruciferous vegetables, high glycemic index and body weigh index). A high incidence of thyroid carcinomas was found in volcanic areas in connection with the effects of heavy metals contained in lava. Another high incidence was recorded in the areas with low average annual temperatures. One of the reasons for the increase in the incidence of thyroid carcinoma is...
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Spinal muscular atrophy
Bohatá, Jana ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder which affects α-motor neurons in anterior horns of spinal cord resulting in progressive muscle weakness. The estimated incidence is 1:10 000 and carrier frequency 1:40-1:60. SMA is classified into four grades depending on the age of onset and its severity. Life expectancy differs according to grade of SMA, patients suffering from the most serious grades live about two years, milder could live to adulthood. This disorder is caused by mutation of the SMN1 gene which is located on the fifth chromosome. In the majority of cases the type of mutation is homozygous deletion in SMN1 gene. Keywords: Spinal muscular atrophy; neuromuscular disorder; alpha motor neurons; autosomal recessive disorder; SMN1; SMN2
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Microduplications on human chromosomes
Štolová, Lucie ; Šolc, Roman (advisor) ; Brynychová, Iva (referee)
Microduplications are small chromosomal aberrations, for whose detection it is necessary to use molecular cytogenetic methods (FISH, CGH) instead of common cytogenetic methods. Together with microdeletions, they are most often mediated by non-allelic homologous recombination during meiosis. They occur at many places in human genome and the duplications of some chromosomal regions are responsible for syndrome emergence. Some of the genes, that are included by microduplications, are dosage sensitive and they cause the pathological phenotype. As a result of development of molecular genetic methods and their usage in studies targeted on microduplications, it comes out, that presence of microduplications on the human chromosomes was undervalued, especially because of their minor clinical significance compared to microdeletions.
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