The differences in quantities of α2‐and α1‐globin gene variants in heterozygotes

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Abstract
We have identified through sequencing of amplified DNA the mutations in the alpha 2- and alpha 1-globin genes in 63 individuals with a heterozygosity for an alpha chain abnormal haemoglobin (Hb). Moreover, we developed a reverse transcription/polymerase chain reaction (RT/PCR) based procedure for the determination of the alpha 2- and alpha 1-mRNA ratio in normal individuals. The numbers of alpha 2 and alpha 1 variants were nearly the same. The average percentage of the abnormal Hb in heterozygotes with alpha 2 mutations (23.5%) was slightly higher than that in heterozygotes with alpha 1 mutations (19.7%) (stable Hbs only). These percentages correspond to a ratio of alpha 2 to alpha 1 of 1.19 to 1 at the protein level. Variations in the number of active alpha-globin genes and in the stability of the variants (greatly) affected the percentages of the abnormal protein. The average ratio between the alpha 2- and alpha 1-mRNAs in 12 normal individuals was 2.6-2.75 to 1, about as expected from published data, and 2.0 to 1 for two persons with an alpha-thalassaemia-2 (alpha-thal-2) (-3.7 kb) heterozygosity. The high relative mRNA (alpha 2) level which is about twice the relative level of the alpha 2 protein suggests a less efficient translation of the alpha 2-mRNA.