Ph.D. / Heat shock proteins (HSP) (in particular hsp70) are increasingly synthesised during and following exposure to stressful insults, playing an important role in protection and adaptation. Protective effects of HSP concerning infection and immunity include self/non-self discrimination, enhancement of the immune response, immune protection, thermotolerance and cytoprotection from inflammatory mediators (reactive oxygen species and cytokines). Considering the general protective role of hsp70 and its specific immunological functions, including antigen processing and presentation, variation in hsp 70 genes may contribute towards differential coping with stress and disease susceptibility. In humans, three members of the hsp70 gene family, hspl0-1, hsp70-2 and hsp70-hom, were mapped to the MHC class Ill region approximately 280 kbp centromeric to the TNFa gene and 92 kbp telomeric to the C2 gene. Polymorphisms in MHC-Iocalized hsp70 genes have been implicated in susceptibility to a number of diseases, independently or in combination with class II polymorphisms due to linkage disequilibrium (LD). MHC alleles are most often associated with immunosuppressive diseases. Tuberculosis (TB) has a strong immunological basis, involving cell-mediated immunity with human leukocyte antigen (HLA) variants implicated in its susceptibility/resistance. In the light of the above, the role of hsp70 polymorphism in TB susceptibility, alone or in combination with MHC class II alleles, was investigated through the following objectives: 1) Typing of hsp70 gene polymorphism (hsp70-1, hsp70-2 and hsp70-hom) in controls and TB cases from the Cape Coloured population of South Africa 2) Comparison between Cape Coloureds and Caucasoid populations with regard to hsp70 allele and genotype distribution 3) Studying linkage disequilibrium between members of MHC class II (HLADRB1) and Ill (hsp70) alleles in the Cape Coloureds 4) Simulation of MHC class II and Ill haplotypes in this particular population Hsp70 polymorphism was studied in controls (n=106) and TB cases (n=107) from the complex hybrid Cape Coloured population inhabiting the Western Cape region of South Africa - a population showing increased susceptibility to TB. PCR-RFLP and PAGE analysis were used to determine the hsp70 allele frequencies and genotype distribution of the individuals studied, while linkage disequilibrium between MHC class II and Ill, and within class Ill alleles, was investigated using the software "Graphical Overview of Linkage Disequilibruim" (GOLD). Haplotypes comprising MHC class II and Ill alleles were simulated using the software PHASE.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:7271 |
| Date | 10 November 2011 |
| Creators | Boshoff, Tuschka |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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