Abstract
We have studied 31 β-thalassaemia intermedia, 30 β-thalassaemia major patients and 50 normal individuals from Turkey, determining the relationship between the nucleotide variations in β-globin gene cluster, the altered levels of foetal haemoglobin and the relative ratios of β- and γ mRNAs. We have found in β-thalassaemia intermedia patients with high foetal haemoglobin expression that the three nucleotide variations in the 5′ sequences of the gamma globin genes, A→G at Gγ − 1396, the T→C at Aγ − 228, and the GA→AG at Aγ − 603/4, are linked to haplotype II in haplotypic homozygotes and the (AT)8N14(AT)7 motif in βLCR. Conversely, the three single nucleotide substitutions in the 5′ sequences of gamma globin genes, the G→A at Gγ − 1225, the A→G at Aγ + 25 and the C→G at Aγ − 369, which have a strong linkage with haplotype I, V or VI in haplotypic homozygotes and the (AT)10N12(AT)12 and the (AT)9N12(AT)12 motifs in HS-2 of βLCR are all associated with low foetal haemoglobin levels. The number of nucleotide changes in β-globin gene cluster implied in our study are not the primary cause of the differences in haemoglobin F levels. They perhaps may contribute to the variations in the clinical severity observed among β thalassaemia intermedia and major patients with other yet unknown gene conversions.
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Samakoglu, S., Philipsen, S., Grosveld, F. et al. Nucleotide changes in the γ-globin promoter and the (AT)xNy(AT)z polymorphic sequence of βLCRHS-2 region associated with altered levels of HbF. Eur J Hum Genet 7, 345–356 (1999). https://doi.org/10.1038/sj.ejhg.5200284
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DOI: https://doi.org/10.1038/sj.ejhg.5200284
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