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Immunopathological and immunogenetic aspects of haematopietic stem cell and solid organ transplantations
Jindra, Pavel ; Boudová, Ludmila (advisor) ; Fakan, František (referee) ; Slavčev, Antonij (referee)
The genetic diversity of KIR genes and genotypes resembles of the HLA. Although the genes encoding KIR and HLA are located in different chromosomes and segregate independently, there is some evidence of some kind of co-evolution. Therefore, one could expect reduced KIR diversity within the HLA restricted population. A total of 41 unrelated individuals homozygous for ancestral HLA haplotype AH8.1 (HLA-A*0101-Cw*0701-B*0801- DRB1*0301-DQB1*0201), were typed for KIR genes. Over all, fourteen different genotypes were identified. The observed frequencies of KIR genes and genotypes composition generally mirror the published frequencies in Caucasians. Non-framework genes with frequency of more than 90 % included KIR2DL1, KIR2DL3, KIR3DL1, KIR2DS4 and KIR2DP1. Except for the KIR2DS4, all activating genes presented frequencies bellow 50 %. KIR2DS5 was the least frequent among activating genes (17 %), whereas KIR2DL5 (37 %) among inhibitory ones. The most frequent (39 %) was AA genotype. 22 individuals (54 %) had a copy of KIR haplotype A and B (AB genotype), whereas 3 (7%) were homozygous for B (BB genotype). Nine of 14 reported genotypes occurred only in one individual. Comparing with published and recorded genotypes (www.allelefrequencies.net), 5 genotypes were reported in less than 20 individuals worldwide and...
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Laboratory Diagnostics and HLA Typization of Patients with Rheumatoid Artritis.
Škoda, Marek ; Půtová, Ivana (advisor) ; Slavčev, Antonij (referee)
This work studies the relationship between DRB1 alleles and production of clinically most important autoantibodies in patients with rheumatoid arthritis (RA). A group of 81 patients with RA were diagnosed in immunological laboratory and genotyped. The prevalence of most often tested analytes were determined: antinuclear antibodies (ANA), rheumatoid factor (RF), anti-CCP antibodies and anti-MCV antibodies. HLA-DRB1 alleles were detected using PCR-SSP low resolution. The aim of this study was to determine the frequency of DRB1 alleles in Czech patients and to investigate the relationship between DRB1 alleles and production of particular antibodies. The frequency of HLA-DRB1*01 and HLA-DRB1*04 alleles was significantly increased in RA patients compared to healthy subjects. In contrast, the frequency of DRB1*15 allele was significantly reduced. Studying the relationship between DRB1 alleles and presence of antibodies showed a significantly increased frequency of DRB1*04 allele in patients with positive ACPA antibodies (anti-CCP, anti-MCV). Regarding other antibodies (ANA, RF), no relationship between their production and presence of DRB1 alleles was found. Comparison of anti-CCP and anti-MCV antibodies levels between groups of RA patients with the presence and absence of DRB1*04 alleles showed no difference....
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Genetic aspects of posterior polymorphous corneal dystrophy
Lišková, Petra ; Filipec, Martin (advisor) ; Čejková, Jitka (referee) ; Slavčev, Antonij (referee)
Posterior polymorphous corneal dystrophy (PPCD) is regarded as a rare autosomal dominant disorder, affecting both the corneal endothelium and Descemet's membrane. However, in the Czech Republic, PPCD is one of the most prevalent corneal dystrophies. The first phase of the project involved the phenotyping of Czech patients with PPCD and the collection of samples for further genetic analysis. The second phase involved determination of the PPCD chromosomal locus in two large families by using linkage analysis followed by positional candidate gene screening. In total 20 PPCD families with two or more affected members were ascertained. PPCD was diagnosed in 104 individuals, of these 82 provided peripheral blood sample for DNA isolation. Linkage analysis was performed on 52 members in two families that lead to the delineation of the PPCD locus to a 2.7 cM interval on chromosome 20p11.2, between flanking markers D20S48 and D20S139. This resulted in the exclusion of VSX1, which had previously been associated with PPCD, as the disease-causing gene in both families. Five positional candidate genes within the 2.7 cM genetic interval were screened for mutations in two probands from these families by the direct sequencing of the coding regions and no pathogenic mutations were identified. In summary, refinement of the...
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