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Bovine mastitis is the most common bovine disease. IR genes (Immune response genes) are used to resist the immune response. The aim of this work is to describe these genes and their role in immune responses. The complexity of immune responses and resistant polygenic features make it difficult to understand all future comers in the mammary gland. The immune responses describe the components of cellular and humoral immunity that are involved in the defense of the mammary gland. Identification of genomic variants associated with resistance is still trying to find and identify other genes that affect mastitis. Whole genome association studies (GWAS), which use SNP fields, are a valuable tool in these studies. This method uses the phenotypic and genotypic characteristics of individuals. Thanks to GWAS several candidate genes for bovine mastitis resistance have already been identified.

The genes of the major histocompatibility complex are located on the short arm of chromosome 6 and encode surface glycoproteins (HLA glycoproteins), which ensure the presentation of self and foreign peptides on the cell surface. These glycoproteins are subsequently recognized by T-lymphocytes and by other cells of the immune system. When the HLA-peptide complex is recognized as foreign, T-lymphocytes and other components of the immune system are activated, and the foreign cell is destroyed. Therefore, in hematopoietic stem cell transplantation (HSCT), HLA incompatibility between donor and recipient causes a strong immune response against the transplanted cells, and is therefore a major criterion in selecting suitable stem cell donors. This work briefly summarizes the current knowledge about the structure and function of HLA class I and class II antigens. The work focuses on HLA typing techniques to help understand the HLA system, which include serological typing methods, as well as modern molecular typing methods based on PCR and next-generation sequencing, and their relevance for HSCT. We also focus on HSCT processes and preparatory therapy, but the main emphasis is on the importance of HLA incompatibilities between stem cell recipients and donors and their effect on HSCT outcome.

The broader purpose of the work is to find and interpret polymorphism in the genes of natural immunity of cattle to be used to improve disease resistance. The NGS method on the PacBio platform was applied for the resequencing of the gene for the key receptor of innate immunity TLR2 and two genes coding for the components of the downstream transcriptional factor NF-κB. In the population of 149 bulls of the Czech Simmental breed, 22 polymorphisms were found in the gene NFKB1 (5 new), while in the NFKB2 gene 13 SNP were found (10 new). 21 SNP were found in the TLR2 gene (3 new). Of the 56 found polymorphisms, 6 SNPs were nonsynonymous. One SNP leads to a change R474G in the NFKB1 product and five to changes E63D, R152Q, I211V, R563H and H665Q in the protein TLR2. Knowledge of the haplotypes facilitated the development of individual genotyping reactions. In TLR2, a high number of haplotypes was detected, both from the PacBio reads and the statistical reconstruction. In addition, two clusters of haplotypes were ditinguished inTLR2, possibly due to diversifying selection or introgression. The knowledge of genetic diversity in the population allows for the planned association studies with health data. Localization in functional domains allow to define the change with the greatest effect, in particular...

DNA sequencing is a molecular genetic method that results in data about sequence and type of nucleotides present in a given sample of deoxyribonucleic acid (DNA), a molecular carrier of genetic information. These data are frequently of a crucial value for many fields; research, medicine, industry, criminalistics or others. During a long period of time almost all the sequencing was performed using a method invented by Frederick Sanger in the 70's, a technique that uses modified nucleotides that once incorporated into a DNA strand prevent this from further elongation. DNA synthesis in presence of such nucleotides leads to a formation of a mixture of fragments of different lenght that are electrophoretically separated by lenght and the sequence is read from the resulting gel. Since the principle of this method entails some inherent drawbacks (e.g. low throughput and coverage) a significant effort is made lately to develop alternative sequencing approaches. These methods colectively refered to as next-generation sequencing (NGS) use several technologies in order to overcome the limitations of the Sanger sequencing. This thesis discusses the most important NGS methods and focuses on their possible application for sequencing of immunoglobulin and T-cell receptor gene rearrangements, an area of undisputable...

Interactions between hosts and their parasites are considered to be one of the major forces driving animal evolution. It can be assumed that the evolutionary changes will occur especially in host molecules directly involved in these interactions. The first line of host defense is formed by innate immunity receptors among which also pattern recognition receptors (PRRs) belong. PRRs detect the presence of parasites at the beginning of their invasion by binding characteristic structures of their bodies (so called pathogen-associated molecular patterns, PAMPs, e. g. lipopolysaccharide, flagellin or peptidoglycans) or abnormal self molecules (damage-associated molecular patterns, DAMPs, e.g heat shock proteins). Although this mechanism of immune system activation is based on the recognition of ligands that are relatively evolutionarily conservative in pathogens, growing body of evidence suggests that PRRs are highly polymorphic on both interspecific and intraspecific level. High frequencies of minority alleles can be observed in most populations studied. It has been proven that particular alleles of many PRRs may associate with increased or decreased resistance to various infectious or autoimmunity diseases. Relationship between polymorphic receptor and a disease could be the main force, which shapes the...

The cell reaction to chemotherapy is based on certain general biological principles. The genetic structure of cell populations, their actual reaction to chemotherapy and the prognosis of their development are not accidental. They are determined by previous exposures to chemotherapeutic agents and thus their evolutional experience on Darwinian principles. Chemotherapy occurs always in a defined environment of the host with his active participation. A genetic variability in the host reaction to chemotherapeutic interference also exists and which in the long-term perspective is also of evolutional nature. The complex of evaluation of therapeutic procedures thus involves evaluation and influencing of the host and his variability (immunotherapy). Understanding of molecular mechanisms of the pathogenesis of disease, definition of specific genes, their expression, the role of their products and definition of possible targets of chemotherapy is at present a realistic goal of application of genomics and proteogenomics in medicine. The new philosophy in medicine is thus based on respecting individuality in diagnosis, treatment and prognosis. We only can wish that the trend of respecting individuality will be applied in the future, and not only in medicine.