Inheritance studies have previously been undertaken at the South African Sugar Association Experiment Station (SASEX) under irrigated conditions. Since most sugarcane is grown in South Africa under dryland (raingrown) conditions, heritability estimates were calculated under these conditions in this study and compared to those previously obtained under irrigated conditions. A sugarcane population consisting of 12 crosses, 32 offspring in each cross, and their parents were planted in the first two selection stages of the SASEX selection programme to ascertain which stage provided the most useful information when selecting parent cultivars. Data collected from Stage 2 was more reliable than data collected from Stage 1. Variance components, narrow and broad sense heritabilities, correlations among traits, and clonal repeatabilities between seasons were determined for 11 sugarcane traits at Stages 1 and 2. These traits studied included: stalk population; stalk diameter; stalk height; cane mass; dry matter % cane; fibre % cane; brix % cane; brix % dry matter; purity; pol % cane; and ers % cane. Narrow sense heritabilities of the sugarcane traits were estimated by mid-parent offspring regression . Alternative heritability estimates were obtained through restricted maximum likelihood (REML) analysis of the unbalanced North Carolina design II at Stage 2. Although narrow sense heritabilities determined by mid-parent-offspring regression were comparable with those previously determined at SASEX and by other workers, REML was more efficient than regression. Use of REML enabled additive and non-additive genetic variance components to be estimated by allocating degrees of freedom to treatments and the interactions between the different treatments. Heritability estimates varied for different traits and compared favourably with those obtained under irrigated conditions and by other workers. Additive genetic variance was more important than non-additive genetic variance for some characters, but not for stalk population, cane mass, and dry matter % cane, for which both variances were important. Selection of parent cultivars for all sucrose-related traits, fibre % cane, and stalk diameter should be as successful under raingrown as under irrigated conditions, provided that the environmental variation is determined efficiently under raingrown conditions. Environmental correlations were observed between some traits, particularly between the yield related traits, and may have influenced heritability estimates for those traits determined by mid-parent offspring regression. Stalk diameter, fibre % cane, and brix % dry matter were the most repeatable traits between seasons. Cane mass was the least repeatable trait between Stages 1 and 2 but was highly repeatable between plant (-P) and ratoon (-R) crops of Stage 2. Stalk diameter was positively correlated with brix % dry matter (0.457-P and 0.623-R) and strongly negatively correlated with stalk population (-0.790-P and -0.711-R) and fibre % cane (-0.628-P and -0.651-R). Cane mass was strongly positively correlated with brix % dry matter (0.638-P and 0.679-R). By selecting for brix % dry matter and stalk diameter, indirect selection for cane mass would be possible. Brix % dry matter was determined as the most reliable trait on which to base parental and commercial cultivar selection because it was highly heritable, highly repeatable and highly positively correlated with stalk diameter and cane mass. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1995.

The Elsenburg Merino flock has been divergently selected for the ability of ewes to rear multiple offspring since 1986. Updated genetic trends for reproduction are reported for the Elsenburg Merino resource flock. The objective was to determine whether genetic trends estimated previously for the Elsenburg Merino Resource flock changed significantly with the introduction of genetic material from the industry to the high (H) line. All analyses included the full pedigree file, consisting of 6547 individuals. Heritability estimates were 0.08 ± 0.02 for number of lambs weaned and 0.11 ± 0.02 for corrected weight of lamb weaned. The ewe permanent environment variance was estimated at 0.09 ± 0.02 and 0.11 ± 0.02 for number of lambs weaned and for corrected weight of lamb weaned, respectively. Genetic trends for the H and low (L) lines were divergent (P < 0.05) for all reproduction traits during the period prior to the observed breakpoints. Progress for number of lambs weaned in the H line stabilised after 1999 while a decline in response for weight of lamb weaned in the H line occurred after 2003. The change points may result from reduced selection intensity during the formation of reciprocal crossbred lines, or the introduction of unrelated industry sires in the H line. The pedigree was analysed and inbreeding trends computed for the H and L lines with the aim to test the significance of inbreeding within the lines. The software packages used for the statistical analyses were ENDOG v4.8 and POPREP web analysis software. The average inbreeding coefficients (F) were 1.47% and 0.73% for the divergently selected H and L lines. The rate of inbreeding (ΔF) per generation was 0.5% for the H line and 0.6% in the L line. The overall rates of inbreeding per generation were different in the H and L lines but within acceptable levels. The L line, however, showed an unwanted recent increase in inbreeding that will need to be considered in future. Since 2003, part of the Elsenburg Merino breeding flock was subjected to structured reciprocal within-breed crossing. Lamb survival traits and ewe reproductive performance of purebred (H and L) and reciprocal crosses (HxL and LxH) were evaluated using least squares analyses. Levels of heterosis were also assessed. The mean survival of the two crossbred lines was notably superior to the midparent value in absolute terms, although the contrast did not reach statistical significance (P = 0.098). Further research is required to establish whether this within breed heterosis for lamb survival can be exploited to decrease lamb losses. Reproduction, number of lambs born (NLB) and number of lambs weaned (NLW) in the H line was higher than in the L line (P < 0.05) while the two crossbred lines were intermediate and different from both the H line and the L line (P < 0.05) from the analyses of annual reproduction and overall “lifetime” reproduction across three lambing opportunities. Individual heterosis for annual reproduction was estimated at 2.2% for NLB, 13.8% for NLW and 8.5% for corrected weight of lamb weaned (TWW), with the estimate for NLW reaching significance (P < 0.05). Corresponding estimates for total production over three lambing opportunities were 8.7% for TNLB, 19.1% for TNLW and 13.8% for TTWW, with the estimate for NLW reaching significance (P < 0.05). Ten RAPD markers were used to study molecular divergence between the H and L lines. Phenotypic data on the lifetime reproduction of ewes born in 1999 and 2000 indicated that reproduction in the H line ewes was markedly higher than that of L line contemporaries (P < 0.01). The RAPD assay, conducted on 15 ewes from each line, used eight primers and produced 87% polymorphic loci. The mean coefficient of genetic differentiation between lines (Gst) was estimated to be 0.25. In conclusion, the H and L lines were shown to be divergent for genetic trends and levels of inbreeding. The derived estimates of heterosis may also be used to infer divergence between the lines and significant molecular divergence proven using RAPD assays. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

The thioredoxin system consisting of thioredoxin (Trx), thioredoxin reductase and NADPH plays a significant role in a large number of redox-dependent processes such as DNA synthesis and anti-oxidant defense. Elevated levels of this system have been associated with a number of diseases including cancer and HIV. Understanding the regulation of this network from a systems perspective is therefore essential. However, contradictory descriptions of thioredoxin as both an enzyme and redox couple have stifled the adoption of systems biology approaches within the field. Using kinetic modeling, this discrepancy was resolved by proposing that saturation of Trx activity could be due to the saturation of the Trx redox cycle which consequently allowed development of the first computational models of the thioredoxin system in Jurkat T-cells and Escherichia coli. While these models successfully described the network properties of the thioredoxin system in these organisms, further confirmatory studies were required before this modeling approach could be generally accepted. The aim of this study was to utilize computational and molecular methods to confirm or reject this proposed mechanism for thioredoxin activity. To determine if there is any difference in the kinetic models obtained when thioredoxin was modeled as an enzyme or as a redox couple, representative core models were developed. The data showed that when modeling Trx as a redox couple, the system was able to achieve steady state, there was a re-distribution of Trx into its oxidized form and, thioredoxin reductase affected the rates within the system. On the other hand, when Trx was modeled as an enzyme, the system could not reach a steady state, Trx remained in the reduced form and thioredoxin reductase concentration had no effect on the rates within the system. As these properties could be directly tested invitro, we sought to directly confirm which model was correct. The thioredoxin system from Saccharomyces cerevisiae was cloned, expressed and purified and substrate saturation curves were generated using insulin as a model substrate. The data showed that the system reached steady state and with increasing concentrations of insulin, the system saturated with a progressive re-distribution of the thioredoxin moiety into its oxidized form. Further, increasing the thioredoxin reductase concentration increased the flux through the system. Collectively, the results obtained through invitro analyses provided unambiguous support for the thioredoxin redox couple model. These results will enable the construction of a complete computational model of the yeast thioredoxin system and provide a basis for the analysis of this network in a number of pathologies. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2013.

The biodiversity of Durban (eThekwini municipality) in KwaZulu Natal is primarily threatened by urbanization although other factors such as climate change and the spread of invasive species also pose a significant threat. Knowledge of what species exist within the city is important for biodiversity surveillance, detecting invasive taxa and uncovering cryptic species. Conducting a comprehensive biodiversity inventory is a daunting task, especially for hyperdiverse groups such as terrestrial arthropods, where closely related species can often only be separated by subtle morphological characters. This study investigated whether the barcoding marker, Cytochrome Oxidase C Subunit 1 (COI) can be used to efficiently and accurately delineate species of ants (family Formicidae) in comparison to traditional taxonomic approaches. The feasibility of DNA barcoding for assembling biodiversity inventories for urban areas which could be useful in conservation planning was also evaluated. A total of 619 individuals were sequenced from 23 geographic localities within the eThekwini region and surrounding regions. DNA barcoding revealed 80 provisional species/ “barcode clusters” or monophyletic lineages which could represent distinct species, while morphology revealed 51 different morphospecies. Extrapolation measures of species richness indicated that as many as 153 species of ants could occur in the city. Phylogenetic and phylogeographic analyses were performed on co-distributed species belonging to the genera Lepisiota, Camponotus, Pheidole and Pachycondyla to better understand the spatial distribution of genetic variability in the eThekwini region. Nuclear markers 18S rDNA and 28S rDNA were also sequenced and compared for a subsample of individuals from Camponotus and Pachycondyla. There was genetic variation at COI and the nuclear markers for each of the species examined. In order to fully elucidate the population genetic patterns which could be expected in eThekwini and surrounding regions, further sampling across more localities is essential. The use of more nuclear markers could also assist in uncovering these unique patterns of genetic variation in an urban setting. In this study, the utility of COI as a species diagnostic tool in ants was confirmed. The barcoding library constructed showed promise in highlighting reserves that should be preserved and possible cryptic speciation for further investigation. / M. Sc. University of KwaZulu-Natal, Durban 2014.

Autolysins are enzymes that cleave specific structural components within the bacterial cell wall. They contribute to numerous cellular activities such as cell growth, cell division, peptidoglycan recycling and turnover. In this study, twelve Enterococcal isolates (previously from the genus Streptococcus) were examined for susceptibility to the antibiotics Penicillin G and Vancomycin, using a Disk Diffusion and a Microtitre plate assay. In both methods, all twelve strains were resistant to Vancomycin. Six of these strains were susceptible to Penicillin G. The minimum inhibitory concentration (MIC) values were twice that of the disk diffusion assay values. In the presence of antibiotic, the growth rates for the six strains were halved. Autolysins were extracted from the respective cell cultures using a 4% SDS precipitation method. The protein concentrations were calculated and estimated to be within the range of 5.47- to 6.35 μg/μl. Profiles of the SDS precipitate were analyzed on SDS-PAGE. Autolytic proteins were identified and partially analyzed by renaturing SDS-PAGE (zymograms) using gels containing cell wall substrate. Seven lytic bands of molecular weights 25, 30, 50, 63, 75 95 and 145 kDa (designated Autolysin A to G, respectively) were selected for further analysis. The temporal distribution of the enzymes ranged from the mid exponential phase to the early death phase. The seven proteins were blotted onto polyvinylidene difluoride (PVDF) membranes and excised for N-terminal sequencing. Blast analysis of the respective N-terminal sequences showed autolysins A, C, D, E and F to have 100% similarity to the muramidase, amidase and peptidase from S. cremoris, S. suis, S. pneumonia, S. pyogenes and E. faecium, respectively. Biochemical characterization confirmed autolysins A, B, E and F to exhibit muramidase activity, and autolysin C and G to exhibit peptidase activity. Autolysin D displayed 100% similarity to the protein LytA, a peptidoglycan hydrolase that is known to exhibit amidase activity. Blast analysis could not determine any significant similarities for autolysins B and G to previously identified autolysins, thus indicating they may perhaps be novel autolysins. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2007.

Thesis (MSc)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: The World Health Organisation (WHO) has defined preterm labour as the onset of labour before 37 completed weeks of gestation with an incidence ranging between 5-10%. Although patient care has improved, the rate of preterm birth has slowly been increasing and currently impacts significantly on maternal and fetal mortality and morbidity. The complex condition of preterm labour involves multiple etiologies and risk factors, which complicates the search for candidate markers and / or biomarkers. The aim of this prospective study was to investigate potential genetic associations with preterm labour. The study cohort consisted of consecutive first-time booking, low-risk primigravid pregnant women from a restricted geographical region. The study cohort comprised 421 [306 Coloured and 115 Black] pregnant women presenting at the Paarl Hospital Obstetric clinic. Subsequently, DNA was extracted from whole blood and investigated for a range of known polymorphisms in pro-inflammatory and anti-inflammatory cytokines, as well as the novel LGALS13 gene, for potential variants that may impact on pregnancy outcome. Screening techniques involve combinations of allele-specific PCR amplification, Multiphor SSCP/HD analysis, restriction enzyme analyses and DNA sequencing. A significant association was demonstrated between the IL-1RN*2-allele and adverse pregnancy outcome, mainly in the preterm labour and hypertension group. The presence TNFα-308 A-allele was associated with overall adverse pregnancy outcome and preterm labour. In addition to this, a novel IL-1RN allele was identified in the control group. Mutation screening and subsequent statistical methods revealed an association between a novel LGALS13 exonic variant, 221delT, and preterm labour in Coloured women. Two previouslydocumented intronic variants (IVS2-22A/G and IVS3+72T/A) demonstrated linkage disequilibrium, signifying evolutionary conservation of exon three. Additionally, two novel intronic variants, IVS2-36 G/A and IVS2-15 G/A, demonstrated no association with adverse pregnancy outcome. In this study we identified rare novel exonic variants; two non-synonymous variants in exon three (M44V, [N=2] and K87R, [N=1]) and a silent variant in exon four (P117P, [N=1]) - all identified in individuals from the control cohort. Within coding exon three, an interesting variant [“hotspot”] was identified, which represents six polymorphic bases within an 11bp stretch. No associations were demonstrated with these variants and pregnancy outcome. Furthermore, a previously documented 5' “‘promoter” variant, -98 A/C, was identified and demonstrated no association with adverse pregnancy outcome. However, subdivision of lateonset pre-eclamptic cases revealed a significant association with the A-allele and late-onset preeclampsia. Genotype-phenotype investigation demonstrated association between the IL-10 -1082 A/G, IL-4 C/T and 221delT loci and poor pregnancy progress which manifested as (i) delivery of infants weighing <2000g, (ii) before 37 weeks of gestation. The findings of this study will strengthen our understanding of the pathophysiology underlying pregnancy complications and facilitate the further development of effective treatment strategies to reduce maternal and fetal morbidity and mortality. / AFRIKAANSE OPSOMMING: Die Wêreld Gesondheid Organisasie (WHO) klassifiseer voortydse kraam as kontraksie voor 37 volledige weke, met ‘n insidensie tussen 5-10%. Alhoewel pasiënte-sorg verbeter het, neem die tempo van voortydse geboorte steeds toe, wat ‘n groot impak het op moederstrefte en fetale mortaliteit en morbiditeit. Die komplekse kondisie van voortydse kraam sluit veelvoudige oorsake en risiko faktore in, wat die navorsing van kandidaat en / of biologiese merkers kompliseer. Die doel van hierdie prospektiewe studie, was die potensiële navorsing van genetiese assosiasies met voortydse kraam. Die studie kohort bevat opeenvolgende eerste bespreking van lae risiko primigravida swanger vrouens vanaf ‘n beperkte geografiese omgewing. Die studie kohort beslaan 421 [306 Kleurling en 115 Swart] swanger vrouens teenwoordig by die Paarl Hospitaal Verloskunde kliniek. Vervolgens was DNS geëkstraeer van bloedmonsters en geondersoek vir ‘n verskeidenheid van bekende polimorfismes in pro-inflammatoriese en antiinflammatoriese sitokiene, insluitend die nuwe sifting van die LGALS13 geen potensiaal vir variante wat ‘n impak op swangerskap uitkomste sal hê. Die siftings tegnieke toegepas, sluit in ‘n kombinasie van alleel-spesifieke amplifikasie, Multiphor enkelstring konformasie polimorfisme / heterodupleks analise, restriksie ensiem verterings en volgorde bepalings tegnieke. ‘n Betekenisvolle assosiasie was gedemonstreer tussen die IL-1RN*2-alleel en nadelige swangerskap, beperk tot voortydse kraam en die hipertensie groep. Die teenwoordigheid van die TNFα-308 A-alleel was geassosieer met algehele nadelige uitkomste en voortydse kraam. Daarby, was ‘n nuwe IL-1RN alleel geïdentifiseer in die kontrole groep. Mutasie sifting en opeenvolgende statistiese metodes, het ‘n assosiasie getoon tussen ‘n nuwe LGALS13 koderende variant, 221delT, en voortydse kraam in Kleurling vrouens. Twee voorafbeskryfde introniese variante (IVS2-22 A/G en IVS3+72 T/A), het ‘n betekenisvolle bewys opgelewer dat daar koppelings-onewewig bestaan tussen hierdie variante, en toon evolusionêre konservasie van ekson drie. Addisioneel was twee nuwe introniese variante ontdek, IVS2-36 G/A en IVS2-15 G/A, wat geen assosiasie getoon nie. In hierdie studie het ons ‘n nuwe seldsame koderende variante geïdentifiseer in die kontrole groep, waarvan twee nie-sinonieme variante was in ekson drie (M44V, N=2 en K87R, N=1) en ‘n stil variasie in ekson vier (P117P, N=1). Geleë in die koderende area van ekson drie, was ’n interessante variant [“hotspot’] ontdek, waarvan ses basisse in ‘n 11 basis paar area polimorfies is. Geen assosiasie was getoon met hierdie variante en swangerskap uitkomste nie. Verder was ‘n voorafbeskryfde 5' ‘promotor’ variant, -98 A/C, geïdentifiseer wat geen assosiasie getoon met nadelige swangerskap uitkomste nie. Onderverdeling van laat-aanvangs preeklampsie, het getoon dat die A-alleel ‘n betekenisvolle assosiasie getoon het met die ontwikkeling van laat pre-eklampsie. Genotipe-fenotipe interaksies het ’n assosiasie getoon tussen die IL-10 -1082 A/G, IL-4 C/T en 221delT lokusse en nadelige swangerskap uitkomste, wat manifesteer as (i) kraam van suigelinge wat <2000g weeg, (ii) geboorte voor 37 weke. Die bevindings van hierdie studie sal ons basiese kennis verbeter oor die patologie beskrywend aan swangerskap komplikasies, asook die fasilitering en ontwikkeling van effektiewe behandelings strategieë, om moederstrefte en fetale mortaliteit en morbiditeit te verminder.

Thesis (MSc (Genetics. Institute of Plant Biotechnology))--Stellenbosch University, 2008. / Sugarcane (Saccharum spp.) is an important crop which is cultivated worldwide for the high sucrose content in its stem. Conventional plant breeding has proven to be very successful over the years with regard to the enhancement of yield characteristics but due to the exhaustion of genetic potential in the commercial sugarcane germplasm recent progress has been slow. Genetic engineering seems to be a more attractive approach to enhance sucrose content and pest resistance in the stems but requires appropriate transgenes and suitable promoter. A promoter is essential to drive the transcription of a gene and is therefore critical to the success of transgenic approaches in sugarcane crop improvement. A negligible number of strong stem-specific promoters is available for use in sugarcane and this is one of the major limitations to genetic engineering. The goal of this project was to isolate a stemspecific promoter from maize and sorghum to drive stem-specific transgene expression in sugarcane. The approach used was to source promoters from non-sugarcane grass species with less complex genomes to simplify isolation and possibly counteract silencing. A cDNA sequence (SS) (EST clone, Accession number AW746904) from sugarcane was shown by Northern and Southern analysis to be stem-specific and to have an appropriately low copy number. The SS gene sequence was not expressed in the leaves of maize, sorghum or the sugarcane cultivars and prominent expression was observed only in the stems of the sugarcane hybrids N19 and 88H0019. The SS gene sequence was used to isolate its upstream regions from a Lambda genomic library of maize (Zea mays) and a sorghum (Sorghum bicolor) Bacterial Artificial Chromosome library (BAC). Of the four sorghum and six maize clones obtained in this study, a 4500 bp maize genomic DNA fragment (λ5) was sub-cloned in three fragments into separate pBluescript vectors using the ‘forced’ cloning approach for sequence and database (BLASTN) analysis. This revealed the complete SS gene sequence (975 bp), the promoter and a 300 bp intron region. A stretch of DNA sequence from nucleotides 664-3194 from the maize clone 5 sequence was designated the maize5-pro. Following sequence alignment of the maize and sugarcane promoter regions, significant sequence identity (68%) was observed between nucleotide 1675 and 3194 in maize and nucleotide 1506 and 2947 in sugarcane. The distance between the putative TATA-box and the TSS for this promoter (30 bp) was found to fall within the expected range of 32± 7 bp. The promoter region was analysed for possible cis-acting regulatory elements and revealed several promoter elements that are common in other plant promoters. The comparisons made between the putative transcription factors in maizepro-5 and the sugarcane promoter show that both promoter sequences are very similar as they share ten of the same transcription factors. However, the transcriptional factors WBOX, SRE and SP8BFIBSP8BIB are unique to the maize5-pro and the TAAG motif to the sugarcane promoter. Primers were designed with appropriate restriction sites and the promoter and intron (2850 bp) region was amplified by PCR (Polymerase chain reaction). The amplified fragment was fused inframe to the GUS reporter gene encoding β-glucuronidase to produce a transformation test vector. This will be used in future work to assess the functionality of the promoter through the production of stable transformants in which GUS activity can be measured in a range of tissues.

Thesis (MSc (Genetics))--University of Stellenbosch, 200 5. / The Lr19 translocation is associated with deleterious agronomic effects and as a result modified forms of the translocation have been derived by different researchers in an attempt to remove the genes responsible.

Thesis (MSc (Genetics))—University of Stellenbosch, 2007. / The porphyrias are a group of genetic disorders arising from mutations in either one of the final seven genes encoding the haeme synthesis enzymes. These disease-causing mutations lead to an enzyme deficiency that disrupts normal haeme production, resulting in clinical features due to the subsequent accumulation of porphyrin precursors. Like most of the porphyrias, variegate porphyria (VP) is characterized by high inter- and intra- familial clinical variability, with no apparent genotype-phenotype correlation. The delta-aminolevulinate synthase-1 gene (ALAS1) is an apparent candidate gene to explain the variable clinical expression observed in VP, since it encodes the first and rate-determining enzyme of haeme synthesis. Several studies have defined important regulatory elements for the human-, rat- and chicken ALAS1 gene that regulate expression patterns of this gene. It was hypothesized that in VP individuals, variants within/near critical regulatory sites might alter the transcription rate of this gene, and consequently increase/decrease the amount of haeme precursors accumulating as a result of the defective haeme synthesis enzyme. The aim of this study was to identify genetic variants that could influence gene expression in the proximal promoter area of the ALAS1 gene, as well as the two ALAS1-drug responsive enhancer sequences (ADRES) located further upstream. DNA (2133 bp per patient) of 19 clinically defined VP patients was analysed by polymerase chain reaction (PCR) and semiautomated DNA sequencing. Subsequently, in silico analyses using appropriate software programs, and in vitro studies using the luciferase reporter system, were performed to investigate the functionality of the identified variants on ALAS1 gene transcription...

Thesis (MSc (Genetics))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: Oesophageal cancer (OC) is characterised by the development of malignant tumours in the epithelial cells lining the oesophagus. It demonstrates marked ethnic variation, with squamous cell carcinoma (SCC) being more prevalent in the Black population and adenocarcinoma (ADC) occurring more often in Caucasians. The aetiology of this complex disease has been attributed to a variety of factors, including an excess of iron (resulting in increased tumourigenesis), oesophageal injury and inflammation. The present study attempted to determine the mutation spectrum of the regulatory and coding regions of the ceruloplasmin (CP) gene, involved in iron metabolism, in the Black South African OC population. The patient cohort was comprised of 96 (48 male and 48 female) unrelated individuals presenting with SCC of the oesophagus. The control group consisted of 88 unrelated, healthy population-matched control individuals. The techniques employed for mutation detection in this study included polymerase chain reaction (PCR) amplification, heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis followed by bidirectional semi-automated DNA sequencing analysis to verify the variants identified. Mutation detection of CP resulted in the identification of fourteen previously described (5’UTR-567C→G, 5’UTR-563T→C, 5’UTR-439C→T, 5’UTR-364delT, 5’UTR-354T→C, 5’UTR-350C→T, 5’UTR-282A→G, V223, Y425, R367C, D544E, IVS4-14C→T, IVS7+9T→C and IVS15-12T→C) and four novel (5’UTR-308G→A, T83, V246A and G633) variants. Statistical analysis revealed that two of the novel variants were significantly associated with OC in this study; the promoter variant 5’UTR-308G→A (P=0.012) and the exonic variant G633 (P=0.0003). It is possible that these variants may contribute to OC susceptibility in the Black South African population. OC symptoms generally present late in the development of the disease, and as a result treatment after diagnosis is highly ineffective. Early detection of symptoms and subsequent treatment is therefore the most effective manner of disease intervention. In high incidence areas, such as the Transkei region of South Africa, the implementation of a screening programme would be the ideal way to achieve this goal. The information that can be gathered from the identification of potential modifier genes for OC can lead to improvements in early detection, which in turn may lead to advancements in the treatment and counselling to individuals with OC. To our knowledge, this is the first study concerning CP and its effects on iron dysregulation in the Black South African population with oesophageal cancer. / AFRIKAANSE OPSOMMING: Oesofageale kanker word gekenmerk deur die ontwikkeling van kwaardaardige gewasse in die epiteelweefsel van die oesofageale voering. Hierdie siekte demonstreer opvallende etniese variasie, met plaveisel selkarsinoom meer algemeen in die Swart populasie en adenokarsinoom meer algemeen in die Kaukasiese populasie. Die ontwikkeling van hierdie komplekse siekte word aan ‘n aantal faktore toegeskryf, insluitend ‘n oormaat yster (wat lei tot ‘n vermeerdering van gewasse) en oesofageale besering en -ontsteking. Die doel van die hierdie studie was om die mutasie spektrum van die regulatoriese- en koderingsarea van die ceruloplasmin (CP) geen, betrokke in yster metabolisme, in die Swart Suid Afrikaanse oesofageale kanker populasie te bepaal. Die pasiënt groep het bestaan uit 96 (48 manlik en 48 vroulik) onverwante individue met plaveisel selkarsinoom van die oesofagus. Die kontrole groep het uit 88 nie-geaffekteerde onverwante, populasie spesifieke individue bestaan. Die tegnieke aangewend vir mutasie deteksie in hierdie studie sluit in polimerase kettingsreaksie amplifikasie, heterodupleks enkelstring konformasie polimorfisme analise en restriksie fragment lengte polimorfisme analise, gevolg deur tweerigting semi-geoutomatiseerde DNS volgorde-bepalingsanalise om die geïdentifiseerde variante te bevestig. Mutasie deteksie van CP het tot die identifikasie van veertien reeds beskryfde (5’UTR-567C→G, 5’UTR-563T→C, 5’UTR-439C→T, 5’UTR-364delT, 5’UTR-354T→C, 5’UTR-350C→T, 5’UTR-282A→G, V223, Y425, R367C, D544E, IVS4-14C→T, IVS7+9T→C en IVS15-12T→C) en vier nuwe (5’UTR-308G→A, T83, V246A en G633) variante gelei. Statistiese analise het getoon dat twee van die nuwe variante betekenisvol geassosieerd was met oesofageale kanker in hierdie studie; die promotor variant 5’UTR-308G→A (P=0.012) en die eksoniese variant G633 (P=0.0003). Dit is moontlik dat hierdie variante mag bydra tot oesofageale kanker vatbaarheid in die Swart Suid Afrikaanse populasie. Oesofageale kanker simptome vertoon gewoonlik op ‘n latere stadium in die ontwikkelingsproses van die siekte, en as ‘n gevolg is behandeling na diagnose hoogs oneffektief. Vroegtydige identifikasie van die simptome en daaropvolgende behandeling is die mees effektiewe manier vir ingryping. In hoë voorkoms streke, soos die Transkei gebied van Suid Afrika, sal die implementasie van ‘n siftingsprogram die ideale manier wees om hierdie doel te bereik. Die inligting wat dan versamel word, insluitend identifisering van modifiserende gene vir oesofageale kanker, kan lei tot ‘n verbetering in vroegtydige deteksie van die siekte. In effek kan dit dan lei tot beter behandeling en berading vir individue met oesofageale kanker. So ver ons kennis strek, is hierdie die eerste studie wat CP en sy effek op yster disregulasie in die Swart Suid-Afrikaanse populasie met oesofageale kanker behels.