Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The repeated purine-pyrimidine motif (AT)xTy at the region -530bp 5' to the beta-globin gene is regarded as the binding site for BP1, a transcriptionally repressive nuclear protein. In present study, the rearrangement patterns of the -530 motif in the Chinese population, including 43 patients with various hemoglobinopathies and part of their relatives (34), as well as 20 hematologically normal individuals, were investigated with the method of ds-DNA cycle sequencing. The results showed that the -530 motif in Chinese people had three major variation types-(AT)8T5, (AT)7T7 and (AT)9T5. Besides, a novel rearrangement type, (AT)10T3, was found in a hematologically normal family. Furthermore, the analysis of haplotype between the beta-globin structural loci and the -530 motif rearrangement indicated that linkage disequilibrium existed between three mutant beta-globin genes (i.e., IVS-II-654(C-->T), CD41-42(-4bp) and HbE), and three -530 motif rearrangement types (i.e., (AT)8T5, (AT)7T7 and (AT)9T5)7 respectively.
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PMID:[A study of the variation of the (AT)xTy motif-530bp 5' to the beta-globin gene in the Chinese population]. 908 21

Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant beta-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle beta-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein gamma-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.
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PMID:Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors. 961 20

The correction of mutant beta-globin genes has long been a therapeutic goal for patients with beta-thalassemia or hemoglobinopathies. The use of homologous recombination (HR) to achieve this goal is an attractive approach because it eliminates the need to include regulatory sequences in the therapeutic construct, and it eliminates mutagenesis induced by random integration. However, HR is a very inefficient process for gene correction, and its efficiency is probably locus dependent. The length of targeting arms is thought to be a determinant of targeting efficiency, so we compared the ability of standard (8-kb) versus very long (16-, 24-, and 110-kb) regions of homology to correct a mutant murine beta-globin gene in embryonic stem cells. Increasing the length of the targeting sequences did not increase the efficiency of HR in this locus, suggesting that alternative approaches will be required to improve the efficiency of this approach for globin gene correction.
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PMID:Long targeting arms do not increase the efficiency of homologous recombination in the beta-globin locus of murine embryonic stem cells. 1273 Jan 7

Hemoglobinopathies represent the most common genetic disorder worldwide, with a higher prevalence among populations with a history of malaria endemicity. More than 690 mutations in the human beta-globin gene are usually the cause of beta-type hemoglobinopathies. Here, we report a rapid and highly sensitive beta-globin gene mutation screening approach based on denaturing high-performance liquid chromatography (DHPLC), which contrary to the previously described ones can be used in every HPLC apparatus. The sensitivity and specificity of the method were tested in 120 healthy Greek subjects and 25 beta-thalassemia heterozygotes and homozygotes, in which 11 different beta-globin sequence variations had been previously characterized by denaturing gradient gel electrophoresis. Using this method, we were able to rapidly identify the commonest beta-globin gene mutations, accounting for more than 90% of the mutant beta-globin alleles reported for the Hellenic population. Compared to classical mutation screening approaches, our DHPLC approach provides the means for rapid, highly sensitive, cost-effective, and semi-automated simultaneous mutational scanning of a large number of samples.
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PMID:A versatile denaturing HPLC approach for human beta-globin gene mutation screening. 1692 51