During development, human beta-globin locus regulation undergoes two critical switches, the embryonic-to-fetal and fetal-to-adult hemoglobin switches. To define the role of the fetal (A)gamma-globin promoter in switching, human beta-globin-YAC transgenic mice were produced with the (A)gamma-globin promoter replaced by the erythroid porphobilinogen deaminase (PBGD) promoter (PBGD(A)gamma-YAC). A...

Species differences in the size or membership composition of multigene families can be attributed to lineage-specific additions of new genes via duplication, losses of genes via deletion or inactivation, and the creation of chimeric genes via domain shuffling or gene fusion. In principle, it should be possible to infer the recombinational pathways responsible for each of these different types o...

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C-->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the in...

T HE THALASSEMIAS are hereditary hemolytic anemias characterized by decreased or absent synthesis of one of the globin subunits of the hemogbobin molecule.’ ln the a-thalassemias, decreased synthesis of a-globin results in accelerated red cell destruction because of the formation of insoluble HbH (f34) inclusions in mature red cells. The greater clinical severity of the fl-thalassemias reflects...

Beta thalassemia is a common monogenic disorder caused by partial or complete reduction of beta globin chains synthesis. In recent years allogeneic bone marrow transplantation (BMT) has been considered to be the successful cure for patients with major, however this restricted due limited number HLA-matched donors. Therefore, molecular approaches including gene therapy direct normal transmission...

T HE DISTRIBUTION of the percentage of a globin variant chains in humans is tnimodal, with maxima around 45%, 33%, and 25%’; the latter value is the most commonly found and comparison with the usual 45%-50% value for f3 globin mutants was the basis for the suggestion2 that a globin genes are duplicated in humans. Thus, the dyploid number of a genes would be 4, one of which should be the mutated...

TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the β-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL...

Genome editing (GE) is one of the most efficient and useful molecular approaches to correct effects gene mutations in hereditary monogenetic diseases, including β-thalassemia. CRISPR-Cas9 has been proposed for effective correction β-thalassemia mutation, obtaining high-level “ de novo ” production adult hemoglobin (HbA). In addition primary causing β-thalassemia, several reports demonstrate tha...

Background: The double heterozygous state of α/β thalassemia may alter the hematological indices and modify the phonotype. In addition, definite characterization of co-inheritance of αand β-thalassemia heterozygous carriers may change the process of genetic counseling. Materials and Methods: An Iranian couple with low hematological indices was analyzed for α-globin gene deletions using multiple...