Three Japanese individuals with homozygous ‘-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the fl-globin gene cluster. Nucleotide sequence analysis of the 6-globin gene cloned from each patient revealed a single nucleotide substitution (T-C) 77 base pairs 5’ to the cap site, just upstream of the CCAAC box...

AIMS To investigate whether it is worthwhile, in areas where thalassaemia is common, to screen for globin gene mutations in subjects with a mean corpuscular volume (MCV) above 80 fL, especially in partners of known thalassaemia carriers. METHODS Blood samples from 95 subjects with MCV between 80 and 85 fL were screened for the presence of alpha globin gene mutations and the haemoglobin (Hb) E...

Hemoglobinopathies such as sickle cell anemia and b-thalassemia result from among the most common single gene defects worldwide. A promising approach for the treatment of these conditions is through the induction of increased fetal hemoglobin (HbF) expression. Hydroxyurea, which is currently part of the standard treatment of sickle cell anemia, causes increased expression of HbF. However, the l...

Thalassemia is a group of hereditary hemoglobin disorders characterized by insufficient production at least one globin chain, resulting in unbalanced chains. Homozygous mutations the β-globin gene, absence β-chain, are main cause β-thalassemia major. Because β-chain major not formed, there an accumulation free α-chains red blood cells, which can trigger apoptosis and hemolysis ineffective eryth...

The a globin genotype of a total of 282 Indians from Orissa state has been analyzed. The overall a thalassemia gene frequency is 0.29. most frequently caused by the a3’7 and a42 deletions. In one family a novel a3” deletion removing the al globin gene with some of its flanking sequences has been found. suggesting further sequence homology of the a globin gene cluster 3’ to the al globin gene. P...

The white blood cell DNA of 36 cord blood samples with Hb Bart’s in the red blood cells was studied for a-globin gene deletions by hybridization of DNA fragments digested by the restriction endonucleases Eco RI, Hpa I. Bam HI, and Bgl II. All 16 DNA samples from cord blood with Hb Bart’s below 3% and no other abnormal hemoglobin had one a-globin gene deletion (athal2), except one which had two ...

We report a new type of deletion of the fi globin gene cluster in the Italian population that confers a phenotype of hereditary persistence of fetal hemoglobin (HPFH) to the carriers. This deletion begins -5 kilobases (kb) 5’ to the #{246} globin gene and ends -30 kb 3’ to the fi globin gene. in close proximity to the 3’ end of an Indian HPFH. In all four previously described HPFH. a repetitive...

Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and beta-thalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from...

HE HUMAN p-GLOBIN locus contains five funcT tional genes arranged 5' E-Gy-Ay-6-P 3' in the order of their expression during development.' Six to 18 kb upstream of the eglobin gene are a series of four DNase I hypersensitive sites that are erythroid specific and developmentally stable, ie, present regardless of which specific globin genes are active.'z3 Reverse genetics experiments have shown th...

An understanding of the human fetal to adult hemoglobin switch offers the potential to ameliorate β-type globin gene disorders such as sickle cell anemia and β-thalassemia through activation of the fetal γ-globin gene. Chromatin modifying complexes, including MBD2-NuRD and GATA-1/FOG-1/NuRD, play a role in γ-globin gene silencing, and Mi2β (CHD4) is a critical component of NuRD complexes. We ob...