Sickle cell disease is characterized by a very heterogeneous clinical course among patients with the same mutations for sickle hemoglobin (HbS). anemia (SCA) hereditary hemoglobinopathy caused homozygosity of point mutation in beta-globin gene, which leads to substitution glutamic acid valine sixth position.

Ten patients with thalassemia intermedia with variable severity and apparent simple heterozygosis for beta0 39 C>T nonsense mutation were submitted to clinical, hematologic and molecular studies. The presence of an unknown molecular defect (silent beta-thalassemia) unlinked to the beta cluster interacting with the heterozygous beta thalassemia, was previously postulated in these families. Analy...

The human beta-globin gene is abundantly expressed specifically in adult erythroid cells. Stage-specific transcription is regulated principally by promoter proximal cis-regulatory elements. The basal promoter contains a non-canonical TATA-like motif as well as an initiator element. These two elements have been shown to interact with the TFII-D complex. Here we show that in addition to the TATA ...

Various mouse erythroleukemia cell lines show unique responses to chemical inducers. Lines 745 and 707, from DBA/2 mice, produced 25%--48% beta-minor and 78%--52% beta-major globin following culture with DMSO. Butyric acid treatment led to approximately 40% beta-minor globin, while induction with hemin resulted in over 80% beta-minor synthesis. Line FSD was developed independently. DMSO inducti...

The molecular mechanisms which govern the develop-mental specificity of human beta-globin gene transcription have been studied in K562 cells, a human eyrthroleukemia line that expresses minimal beta-globin. Protein-binding analysis reveals that the 5' region contains three elements bound by trans-acting factors, beta-protein 1 (BP1) and beta-protein 2 (BP2). In vitro mutagenesis of each individ...

Efficient transfer of the beta-globin gene into primitive hematopoietic progenitors was achieved with consistent and significant expression in the progeny of those cells. Retroviral vectors containing the intact genomic human beta-globin gene and the neomycin (G418)-resistance (neoR) gene were constructed. These gave titers of 10(6) or more neoR colony-forming units/ml when packaged in psi 2 ce...

Many human globin-chain mutants contain amino acid replacements that result from single base changes in the corresponding globin gene. Using recombinants, the coding sequences of each of the alpha-, beta-, Ggamma-, and Agamma-globin genes have now been determined. Those sequences of DNA that are cleaved by a number of specific restriction endonucleases have been identified and accurately positi...

We characterized the molecular defect in a Swiss patient with a spontaneous beta-thalassemia mutation. Cloning and DNA sequencing of her beta-globin gene revealed a new frameshift mutation due to a single nucleotide deletion at codon 64 of the beta-globin gene. Restriction site polymorphism showed that the mutation arose on her paternal chromosome. Direct sequencing of a polymerase chain reacti...

Sickle cell anemia (SS) is associated with abnormalities of the red cell membrane and decreased red cell deformability. The present study assesses globin chain binding to stroma in SS, sickle cell trait (AS), and nonsickling (AA) cells. The results indicate that there is preferential binding of newly synthesized beta(S) globin to red cell stroma in SS cells and preferential binding of beta(S) t...

Hemoglobinopathies are important inherited disorders with high prevalence in many tropical countries. Prediction of protein nanostructure and function is a great challenge in proteomics and structural genomics. Identifying the point vulnerable to mutation is a new trend in research on disorders at the genomic and proteomic level. A bioinformatics analysis was performed to determine the position...