α/β Globin mRNA of β-thalassemia genes with premature termination

Abstract

Mutation of β-globin gene causing translation-premature termination results in significant decrease of the mRNA abundance. This phenomenon arises from the degradation of mutant mRNA by nonsense codon-mediated mRNA decay (NMD). In this study, α/β-globin mRNA ratio was determined by semi-quantitative RT-PCR in β-thalassemia carriers with the β17, β41/42, β71/72 and β27 mutations and in a patient with compound heterozygous β17, β27 mutations. Values were compared with normal individual. The α/β-globin mRNA ratio of normal individual was found to be 0.98 whereas those of heterozygous for β17, β41/42, β71/72 and compound heterozygous β17/β27 were 0.89 1.66 1.60 and 3.09, respectively. Direct DNA sequencing of the cDNA demonstrated mutant mRNA only in the carrier with β17 mutation but not other mutations. This result was in concordance with the α/β-globin mRNA ratio observed. This data indicates that the α/β-globin mRNA ratio is dependent on the type and the location of premature termination mutation and related to some other factors involving NMD mechanism in cells.