Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs...

We report a new type of deletion of the beta globin gene cluster in the Italian population that confers a phenotype of hereditary persistence of fetal hemoglobin (HPFH) to the carriers. This deletion begins approximately 5 kilobases (kb) 5' to the delta globin gene and ends approximately 30 kb 3' to the beta globin gene, in close proximity to the 3' end of an Indian HPFH. In all four previously...

All pharmacologic agents that induce fetal hemoglobin (Hb) have been discovered with in vivo studies of humans, macaques, and baboons. We tested whether transgenic mice carrying human fetal (gamma) globin genes provide a model for studying the pharmacologic induction of HbF in the adult. In initial studies, phenylhydrazine-induced hemolytic anemia, 5-azacytidine, butyrate, or combinations of th...

introduction: beta thalassemia is the most common inherited bloody disorder, affecting synthesis of the beta globin chain of hemoglobin. the type of β-thalassemia mutation affects on the β-globin chain synthesis that appears as β ° ، β + and β ++ -thalassemia. the presence of xmni polymorphic site at the 5 َ region of the g γ-globin gene affects on the rate of g γ chain synthesis and in some con...

Although delta-globin gene (HBD MIM#142000) mutations have no clinical implications, co-inheritance of beta- and delta-thalassemia may lead to misdiagnosis. Among 7,153 samples studied for beta-thalassemia, 205 samples with lower than expected HbA2 levels were selected for our analysis and 183 samples (2.5%) were positive for delta-globin gene mutations. Twelve different mutations were detected...

By sequencing regions flanking the beta-globin gene complex in mouse (Hbbc) and human (HBBC), we have shown that the beta-globin gene cluster is surrounded by a larger cluster of olfactory receptor genes (ORGs). To facilitate sequence comparisons and to investigate the regulation of ORG expression, we have mapped 5' sequences of mRNA from olfactory epithelium encoding beta-globin-proximal ORGs....

Current methods that assay hemoglobin beta-globin chain variants can have limited clinical sensitivity when applied techniques identify only a predefined panel of mutations. Even sequence-based assays may be limited depending on which gene regions are investigated. We sought to develop a clinically practical yet inclusive molecular assay to identify beta-globin mutations in multicultural popula...

Repair of beta-globin pre-mRNA rendered defective by a thalassemia-causing splicing mutation, IVS2-654, in intron 2 of the human beta-globin gene was accomplished in vivo in a mouse model of IVS2-654 thalassemia. This was effected by a systemically delivered splice-switching oligonucleotide (SSO), a morpholino oligomer conjugated to an arginine-rich peptide. The SSO blocked the aberrant splice ...

The beta-globin locus control region (LCR) is the founding member of a novel class of cis-acting regulatory elements that confer high level, tissue-specific, site-of-integration-independent, copy number-dependent expression on linked transgenes located in ectopic chromatin sites. Knowledge from beta-globin and other LCR studies has shed light on our understanding of the long-range interaction b...