Globin gene transfer in autologous hematopoietic stem cells is a promising therapeutic option for subjects with beta-thalassemia major. In this approach, high level, erythroid-specific globin transgene expression should correct ineffective erythropoiesis and hemolytic anemia following the delivery of only 1 to 2 vector copies per cell. The generation of vectors that provide high-level globin ex...

Progress in the functional studies of human olfactory receptors has been largely hampered by the lack of a reliable experimental model system. Although transgenic approaches in mice could characterize the function of individual olfactory receptors, the presence of over 300 functional genes in the human genome becomes a daunting task. Thus, the characterization of individuals with a genetic susc...

Gamma-globin chain synthesis has been evaluated in individual bursts and subcolonies that were generated by normal adult blood BFU-Es in methylcellulose cultures containing semipurified erythropoietin (Ep) and then analyzed via either isoelectric focusing (IEF) of globin chains or immunofluorescence techniques. At variance with previously reported results, based on plasma clot culture and immun...

The developmental stage- and erythroid lineage-specific activation of the human embryonic zeta- and fetal/adult alpha-globin genes is controlled by an upstream regulatory element [hypersensitive site (HS)-40] with locus control region properties, a process mediated by multiple nuclear factor-DNA complexes. In vitro DNase I protection experiments of the two G+C-rich, adult alpha-globin promoters...

So far, more than 800 mutations involving the beta-globin gene have been characterized worldwide. Most of these variants are also carried by patients with Turkish origin, since Turkey is one of the hotspot regions for mutations of the globin genes.1 In the present study, we report a case with an unusual high-performance liquid chromatography (HPLC) pattern who turned out to be a carrier of the ...

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...

HUMAN HEMOGLOBINS and their variants have been the subjects for fruitful clinical and basic research for many years. The knowledge derived from these studies is essential in understanding the relationship between hemoglobin structures and functions. The report on the seminal study of sickle hemoglobin by Pauling et al1 in 1949 provided the first example of molecular disease. With the advances i...

background: thalassemia syndromes are the most prevalent single gene disorders in iran. this study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or xmn1 snp on disease phenotype in a large cohort of iranian patients. subjects and methods: in total, 433 patients were clinically classified into β-thalassemia major ...

A patient with homozygous p thalassemia of Germadtalian descent was found to be doubly heterozygous for the common IVSI-110 G -+ A mutation of the p globin gene and for a novel C -+ T mutation of the proximal CACCC-box of the p globin gene promoter at position -87 relativeto the transcription start site (cap). Transcription analysis in an HeLa cell transfection assay indicated a 45% to 51% resi...

Studies on assembly in vitro of alpha-globin chains with recombinant beta16 Gly-->Asp, beta95 Lys-->Glu, beta120 Lys-->Glu and beta16 Gly-->Asp, 120 Lys-->Glu human beta-globin chain variants in addition to human betaA- and betaS-globin chains were performed to evaluate effects of increased anionic charge in the beta chain on hemoglobin assembly using soluble recombinant beta-globin chains expr...