The β-thalassemia syndromes are heterogeneous autosomal recessive hereditary disorders, caused by alterations in the HBB gene and characterized by absent or reduced β-globin chain synthesis. The β-thalassemia phenotypes are variable, ranging from severe, transfusion-dependent thalassemia major to mild, asymptomatic thalassemia trait. This interpatient clinical variability has swayed researchers...

The αand β-globin gene families of jawed vertebrates have diversified with respect to both gene function and the developmental timing of gene expression. Phylogenetic reconstructions of globin gene family evolution have provided suggestive evidence that the developmental regulation of hemoglobin synthesis has evolved independently in multiple vertebrate lineages. For example, the embryonic β-li...

Beta thalassemia is the  most common autosomal recessive disorder. The present study reports a rare β globin gene mutation, HBB: c.180G>A: codon 59 (AAG/AAA), in a patient from Gilan province, northern Iran. Nucleotide sequencing of amplified DNA belonging to a 35 years old man presenting mild hypochromia revealed a synonymous mutation due to a G>A conversion at the third position of codon 59 o...

The β-globin locus control region (LCR) is contained on a 20 kb DNA fragment and is characterized by the presence of five DNaseI hypersensitive sites in erythroid cells, termed 5′HS1-5. A fully active 6.5 kb version of the LCR, called the μLCR, has been described. Expression of the β-like globin genes is absolutely dependent on the presence of the LCR. The developmental expression pattern of th...

The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LC...

β-thalassemia is the most common inherited disorder characterized by a reduction or absence of β-globin chain synthesis. So far, over 200 mutations have been identified that result in β-thalassemia. Most of the mutations are single nucleotide substitutions or deletions, or insertions in the β-globin gene or its flanking sequences. Heterozygous β-thalassemia usually presents with mild microcytic...

The higher order chromatin structure has recently been revealed as a critical new layer of gene transcriptional control. Changes in higher order chromatin structures were shown to correlate with the availability of transcriptional factors and/or MAR (matrix attachment region) binding proteins, which tether genomic DNA to the nuclear matrix. How posttranslational modification to these protein or...

The human b-globin gene complex spans a region of 70 kb and contains numerous sequence variants. These variant sites form a 58 cluster (58 b-haplotype) and a 38 cluster (38 b-haplotype) with strong linkage disequilibrium among the sites within each cluster, but not between the two clusters. The 9-kb region between the 58 and 38 clusters has been estimated to have rates of recombination that are...

BACKGROUND An improved understanding of the regulation of the fetal hemoglobin genes holds promise for the development of targeted therapeutic approaches for fetal hemoglobin induction in the β-hemoglobinopathies. Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved. METHODS We iden...

Distal enhancers commonly contact target promoters via chromatin looping. In erythroid cells, the locus control region (LCR) contacts β-type globin genes in a developmental stage-specific manner to stimulate transcription. Previously, we induced LCR-promoter looping by tethering the self-association domain (SA) of Ldb1 to the β-globin promoter via artificial zinc fingers. Here, we show that tar...