Nucleotide changes in the gamma-globin promoter and the (AT)(x)N-y(AT)(z) polymorphic sequence of beta LCRHS-2 region associated with altered levels of HbF

Creative Commons License

Samakoglu S., Philipsen S., Grosveld F., Luleci G., Bagci H.

EUROPEAN JOURNAL OF HUMAN GENETICS, vol.7, no.3, pp.345-356, 1999 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 7 Issue: 3
  • Publication Date: 1999
  • Doi Number: 10.1038/sj.ejhg.5200284
  • Journal Name: EUROPEAN JOURNAL OF HUMAN GENETICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.345-356
  • Keywords: beta-thalassaemia, HPFH, HbF, gamma-mRNA, beta-globin gene, gamma-globin genes, beta-globin gene haplotype, SICKLE-CELL DISEASE, BETA-THALASSEMIA MUTATIONS, FETAL HEMOGLOBIN, HEREDITARY PERSISTENCE, NORMAL INDIVIDUALS, BINDING PROTEIN, GENE-CLUSTER, DNA, EXPRESSION, HAPLOTYPES
  • Akdeniz University Affiliated: No

Abstract

We have studied 31 beta-thalassaemia intermedia, 30 beta-thalassaemia major patients and 50 normal individuals from Turkey, determining the relationship between the nucleotide variations in beta-globin gene cluster, the altered levels of foetal haemoglobin and the relative ratios of beta- and gamma mRNAs, We have found in P-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 G gamma-1396, the T-->C at A gamma-228, and the GA-->AG at A gamma-603/4, are linked to haplotype II in haplotypic homozygotes and the (AT)(8)N-14(AT)(7) motif in beta LCR, Conversely, the three single nucleotide substitutions in the 5' sequences of gamma globin genes, the G-->A at G gamma-1225, the A-->G at A gamma + 25 and the C-->G at A gamma - 369, which have a strong linkage with haplotype I, V or VI in haplotypic homozygotes and the (AT)(10)N-12(AT)(12) and the (AT)(9)N-12(AT)(12) motifs in HS-2 of beta LCR are all associated with low foetal haemoglobin levels. The number of nucleotide changes in beta-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 beta thalassaemia intermedia and major patients with other yet unknown gene conversions.