The study has developed a model splicing construct assay system based on splicing misregulation, one of the major molecular features associated with myotonic dystrophy. The splicing construct assay has double reporters for intron 2 splicing in chloride channel (CLCN1). The CLCN1 transgene splicing construct assay was used to transfect wild type and DM fibroblast cell lines and the clones generated showed that it enabled quantification of splicing efficiency in transgene construct. Validation of the DM fibroblasts containing transgene splicing construct was performed by differentiating the DM fibroblasts into myoblasts which exhibited a switch in CLCN1 splicing construct which was consistent with that associated with myotonic dystrophy (DM) condition. The myoblast derived from fibroblasts cell-based gene-splicing assay was subsequently applied in therapeutic screening in small throughput screens of 113 compounds which identified Protein Kinase C inhibitors- hypericin and Ro-31-8220 as potential therapeutic agents. The CLCN1 gene-splicing assay is a good model system for application in therapeutic screening in myotonic dystrophy because its double reporters facilitated quantification of effect putative drug on correction of misregulated splicing.

Polymorphic changes in a given population give rise to genetic variations. These variations account for differences found within a population. One of the most abundant and common genetic variant that occur in the population is the Single Nucleotide Polymorphisms which are point mutations in genes. The study assessed the frequency of single nucleotide polymorphisms in mannose binding lectin (MBL2) gene namely rs8191996, rs1838065, rs8179079 and rs1800450 in 366 adult individuals drawn from Xhosa ethnic group of South Africa. The polymorphisms showed high frequencies in its occurrence which was 0.71, 0.42, 0.71 and 0.73 for rs8191996, rs1838065, rs1800450 and rs8179079 respectively. Additionally, the genotype distribution of these polymorphisms showed a predominance of homozygotes over heterozygotes and were in accordance with Hardy-Weinberg principle. The high frequencies of the MBL2 polymorphisms under study in this population suggest that there is a high incidence of single gene mutations in Xhosa ethnic group which could make the population vulnerable to infection.

Toll-like receptor 2 (TLR 2) genetic polymorphisms are important factors that are involved in the development of clinical tuberculosis. In this study, a single nucleotide polymorphism of the immune response protein molecule, toll-like receptor 2 designated as rs3804100 involving T/C polymorphism was carried out by genotypic analysis of DNA obtained from blood samples of the paediatric population in South Africa consisting of 151 cases and 82 controls for tuberculosis. Genotypic analysis of tuberculosis cases for T/C rs3804100 polymorphism showed genetic frequency of 5% for TT, 90% for CT and 5% for CC genotypes while those of controls were 2% for TT, 91% for CT and 7% for CC genotypes. Statistical analysis of the polymorphic genotypes in cases and controls gave no association with the disease. The result from this study showed that this T/C single nucleotide polymorphism of TLR 2 was not associated with the development of tuberculosis (p= 0.34) in the paediatric population.