Southeast Asian Ovalocytosis (SAO) is an autosomal dominantly inherited, classically asymptomatic condition, that is widespread in Southeast Asian populations of Malasia, Indonesia, Papua New Guinea and the Philippines. Some regions have close to 30% prevalence and this is thought to be due to SAO providing partial protection against malaria. SAO is characterized by rigid, spoonshaped, ovalocytic red blood cells. The underlying defect is a deletion of 27bp in the band 3 gene, resulting in the absence of 9 amino acids (400-408) at the boundary of the cytoplasmic and membrane domains of band 3, causing abnormal structure and function. SAO is tightly linked in all cases to the band 3 Memphis 1 polymorphism, which is a lysine 56 (AAG) –glutamic acid (GAG) substitution. This polymorphism can be inherited independently and the prevalence ranges from about 6-30% according to various populations studied. The presence of SAO in a Cape Coloured family is a recent finding. The purpose of this study was to further investigate the prevalence of SAO and the band 3 Memphis 1 polymorphism in the Cape Coloured population. 20 unrelated individuals with SAO morphology were identified. DNA analysis revealed the 27bp deletion of exon 11 of the band 3 gene in all 20 subjects, which is diagnostic of SAO. This indicates a high occurrence of the SAO mutation in the Cape Coloured population, which is speculated to be due to a founder effect. Some of the clinical features differed from classically described SAO as some individuals showed evidence of haemolysis. Protein analysis showed all 20 individuals to have a reduced band 3 mobility, indicating the band 3 Memphis 1 polymorphism. Detecting the band 3 Memphis 1 polymorphism on a protein level is time consuming and labour intensive, therefore a PCR assay, which utilizes DNA, was developed for the rapid screening of this polymorphism. The PCR assay was based on a nucleotide mismatch which created a Taq 1 restriction site when combined with the band 3 Memphis 1 allele, but not with the wild type allele. Digestion of the PCR product with Taq 1 allowed differentiation between the two alleles. It was established that the band 3 Memphis 1 polymorphism has a high prevalence in the Cape Coloured population as it was detected in 108/326 (33%) of the individuals studied. Analysis indicated the Memphis allele is in Hardy-Weinberg equilibrium. / Prof. T.L. Coetzer Dr. H. Abrahamse
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:4546 |
| Date | 05 September 2008 |
| Creators | Ziervogel, Cheryl Anne |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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