The molecular basis of alpha thalassaemia in a South African population
The molecular basis of alpha thalassaemia in the so-called 'Cape Coloured' population of the Western Cape was investigated. Restriction endonuclease digestion, Southern blotting and hybridisation with alpha and zeta globin-specific probes were used to investigate the incidence of the the various alpha thalassaemia determinants and their disorders. Results indicate that one determinant in this population results from the deletion of a single alpha globin gene on the short arm of chromosome 16. In individuals homozygous or heterozygous for this deletion, digestion with restriction endonuclease Bam H1 shows the presence of a shorter 10,5kb alpha globin-specific fragment as opposed to the 14kb fragment found in normal individuals. Individuals with both alpha globin genes deleted on the same chromosome i.e. the genotype --/aa, were detected and their alpha thalassaemia determinant characterised by: 1. a family study 2. quantification of the alpha/gamma glob in gene ratio, and 3. mapping with the zeta globin probe since the deletion extends into the zeta locus. The --/ alpha thalassaemia determinant was found to be of Southeast-Asian origin. A non-deletion form of alpha thalassaemia was also detected in which the alpha globin restriction map appeared to be normal. This condition may have resulted from a point mutation within the alpha ilobin gene region which affects transcription or RNA processing. The DNA of infants born with detectable levels of Hb Bart's in their cord blood was investigated in order to estimate the frequency of the single and double gene deletions in this population. The results indicate that infants with Hb Bart's in the 4 - 8% range predominantly have the genotype -a/-a. Using the data obtained the incidence of the heterozygote was calculated according to the Hardy-Weinberg equation. The calculated incidence of the heterozygote (-a/aa) was found to be 16,9%.
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Division of Medical Biochemistry and Structural Biology