Synthetic genes encoding the human alpha- and beta-globin polypeptides have been expressed from a single operon in Escherichia coli. The alpha- and beta-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to greater than 5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of alpha- and beta-globin chains and contains...

Persistent expression of the gamma-globin genes in adults with deletion types of hereditary persistence of fetal hemoglobin (HPFH) is thought to be mediated by enhancer-like effects of DNA sequences at the 3' breakpoints of the deletions. A transgenic mouse model of deletion-type HPFH was generated by using a DNA fragment containing both human gamma-globin genes and HPFH-2 breakpoint DNA sequen...

Insights into the evolution of hemoglobins and their genes are an abundant source of ideas regarding hemoglobin function and regulation of globin gene expression. This article presents the multiple genes and gene families encoding human globins, summarizes major events in the evolution of the hemoglobin gene clusters, and discusses how these studies provide insights into regulation of globin ge...

The central mechanism underlying the pathophysiology of the β thalassemias can be related to the deleterious effects of imbalanced globin chain synthesis on erythroid maturation and survival. An imbalance of the α/non-α globin chains leads to an excess of unmatched α globin which precipitates out, damaging membrane structures leading to accelerated apoptosis and premature destruction of the ery...

In humans, the b-globin cluster contains fetal gand g-globin and adult dandb-globin genes. Around the timeof birth, fetal hemoglobin (HbF) is almost completely replaced by adult hemoglobin (HbA) containing 2 b-globin chains. Based upon this developmental transition in hemoglobin production, mutations in the b-globin gene locus can cause a variety of hemoglobinopathies including sickle cell dise...

β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α₂β₂;HbA). Increased levels of fetal hemoglobin (α₂γ₂;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhan...

BACKGROUND Recent studies on the variants in duplicated human alpha globin genes (HBA2 and HBA1) actively target the α-globin gene as molecular modulators for the treatment of β-thalassemia major. Identification of the exact position of variant in HBA1, HBA2 or its patchworks is mandatory to support the therapeutic aims in β-thalassemia major, by identifying specific modulators for the reactiva...

The human gamma-globin gene and its orthologous galago gamma-globin gene evolved from an ancestral epsilon-globin gene. In galago, expression of the gamma-gene remained restricted to the embryonic stage of development, whereas in humans, expression of the gamma-gene was recruited to the fetal stage. To localize the cis-elements responsible for this developmentally distinct regulation, we studie...

The human α-globin gene cluster is located on chromosome 16 pterp13.3, and is arranged in the order, 5’ζ2-ψζ1-ψα2-ψα1-α2-α1-θ1-3’. Recent reexamination of the ψα2 gene revealed that it is expressed at a very low level, and was renamed as mu-globin gene. The cluster was thought to result from duplication events that occurred more than 300 million years ago. Unequal homologous recombinations are ...