Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restriction endonuclease mapping data are presented for the DNA of a young Indian homozygous patient (and his heterozygous parents) who were identified 10 years ago as having a G gamma-hereditary persistence of fetal haemoglobin (Sukumaran et al, 1972). However, the present results indicate a genetic lesion in these persons which is similar to that observed in another Indian with (A gamma delta beta)0-thalassaemia homozygosity (Amin et al, 1979) and is characterized by two relatively short deletions and an inversion involving the A gamma, delta and beta globin genes (Jones et al, 1981a). Some additional blot hybridization studies have provided further data confirming the deletion-inversion hypothesis.
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PMID:Restriction endonuclease gene mapping studies of an Indian (A gamma delta beta)zero-thalassaemia, previously identified as G gamma-HPFH. 620 82

An Italian family in which heterocellular hereditary persistence of fetal haemoglobin (HPFH) interacts with both beta(+)- and delta beta-thalassaemia is described. The index case was an 8 year old girl who was presumed to inherit both heterocellular HPFH and beta (+)-thalassaemia from her mother and delta beta-thalassaemia from her father. She was healthy and never needed blood transfusions. The possible contribution of heterocellular HPFH to the less severe expression of the compound delta beta/beta(+)-thalassaemia heterozygosity is discussed. By DNA analysis the specific delta beta-thalassaemia defect on the gamma delta beta globin gene region has been established. In addition, a previously unreported association of a polymorphic restriction site haplotype with a beta (+)-thalassaemia mutation has been observed.
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PMID:Association of heterocellular HPFH, beta(+)-thalassaemia, and delta beta(0)-thalassaemia: haematological and molecular aspects. 620 62

Restriction enzyme digestion analysis and direct human globin gene cloning have permitted analysis of the physical arrangement of nucleotide sequences within and surrounding the human globin genes. With these methods it has been shown that the linear arrangement 5' to 3' of the globin genes is G gamma-A gamma-delta-beta. The G gamma and A gamma genes are separated by about 3.5 kilobases (kb), while the A gamma and delta genes are 15 kb apart, and the delta and beta 6.5 kb apart. Each of these genes contains a large intervening sequence (IVS) of approximately 1 kb in precisely the same position between condons 104 and 105. In addition, each of these genes has a small IVS between codons 30 and 31. In homozygous delta beta thalassemia DNA, there is deletion of all of the normal delta and beta gene fragments. However, a new fragment 4.2 kb in size containing the 5' end of the delta globin gene is retained. Retention of this fragment in delta beta thalassemia, but not in HPFH is consistent with a role for sequences in this region for limiting gamma globin gene expression. Studies to date suggest that the beta + and beta 0 thalassemias will be due to a heterogeneous group of DNA defects affecting either beta globin gene transcription or beta mRNA processing. In most cases of beta + and beta 0 thalassemia DNA analyzed, there is no detectable deletion of beta or delta genes. In three India beta 0 patients, deletion of the 3' end of the beta gene has been found. Analysis of cloned beta globin genes from a patient with beta + thalasseia shows differences from normal in the fragments generated by restriction enzymes which cut frequently. Whether these differences are responsible for the defect in thalassemia or are polymorphisms unrelated to thalassemia remains to be determined.
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PMID:The organization of the gamma-delta-beta gene complex in normal and thalassemia cells. 625 23

beta globin gene fragments from a patient with homozygous beta+-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro trancription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the beta+-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of beta globin mRNA precursor molecules in beta+-thalassemia.
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PMID:Base substitution in an intervening sequence of a beta+-thalassemic human globin gene. 626 77

Two beta globin genes from patients with the beta(+) thalassemia phenotype have been cloned and sequenced. A single nucleotide change from CAG to TAG (an amber mutation) at codon 39 is the only difference from normal in both genes analyzed. The results are consistent with the assumption that both patients are doubly heterozygous for beta(+) and beta degrees thalassemia, and that we have isolated and analyzed the beta degrees thalassemia gene.
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PMID:Two cloned beta thalassemia genes are associated with amber mutations at codon 39. 627 53

A beta globin gene from a patient with homozygous beta+ thalassemia has been cloned and completely sequenced. No changes from normal are found in the 200 nucleotides 5' to the cap site, in the 3' untranslated region up to the poly A addition site, in the small intervening sequence (IVS 1), or in the coding sequence except for a third base change in codon 2. The only other differences are in the large intervening sequence (IVS 2). One of these, at a position 16 nucleotides from the 5' end of IVS 2, has been reported previously in normal individuals, and is probably a polymorphism. Four other changes, at positions 74, 81, 666, and 705 are also seen in IVS 2. Abnormal beta globin mRNA precursors detected in the bone marrow cells of this patient, and abnormal beta globin RNA splicing observed when this gene is transcribed in a tissue culture system taken together with these IVS 2 changes, suggest that the beta+ thalassemia phenotype is produced by a decrease in normal beta globin mRNA processing.
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PMID:Five nucleotide changes in the large intervening sequence of a beta globin gene in a beta+ thalassemia patient. 628 Jan 38

A symptomless Iranian patient homozygous for beta thalassaemia has haematological changes similar to the beta thalassaemia trait. This remarkably mild phenotype is probably the result of coexistent alpha thalassaemia and increased gamma chain synthesis. Restriction endonuclease mapping analysis of the beta globin genes indicates that the patient is homozygous for a single nucleotide substitution at the 5' donor splice junction in the second intervening sequence of the beta globin gene. No other changes were observed in the non-alpha globin gene cluster. It seems unlikely that the augmented gamma chain synthesis in this patient is related to the molecular defect responsible for this beta o thalassaemia.
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PMID:The molecular basis for beta o thalassaemia intermedia in an Iranian individual. 628 64

Restriction endonuclease analysis has been performed on the alpha and beta globin gene clusters of 57 Cypriots homozygous for beta thalassaemia, 30 with the transfusion dependent form of the condition (thalassaemia major) and 27 who are less severely affected (thalassaemia intermedia). There was a significant difference in the incidence of alpha thalassaemia between the two groups: 14/27 of the patients with thalassaemia intermedia also had deletion forms of alpha thalassaemia, while only 4/30 of the patients with thalassaemia major were similarly affected. Thus in Cypriot patients who are homozygous for beta thalassaemia the co-inheritance of alpha thalassaemia is an important factor in determining the clinical course.
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PMID:Thalassaemia intermedia in Cyprus: the interaction of alpha and beta thalassaemia. 629 30

By using Hph I and Rsa I restriction enzymes and beta globin large intervening sequence as a probe, we have investigated the DNA of 20 Algerian patients with beta(0) or beta(+) thalassemia. In any of them, we detected the nucleotide change which is known to generate an additional Hph I site at the 5' splice junction of the beta globin large intervening sequence and which yields a beta(0) phenotype. In one of them, we detected the nucleotide change which is known to generate an additional Rsa I site within the beta globin large intervening sequence and which is supposed to yield a beta(+) phenotype. These results indicate that these two types of mutation are relatively rare in the Algerian population.
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PMID:Beta thalassemic mutations recognized by DNA mapping with Hph I and Rsa I in the Algerian population. 630 52

A library of genomic DNA was prepared from a patient with beta o Ferrara thalassaemia: random human DNA fragments (15 - 20 Kb) have been joined to phage lambda vectors and cloned has viable phage particles (4). 4x10(5) phages have been screened for their content in beta globin gene sequences, using a human beta cDNA plasmid (5) as hybridization probe. Five positive clones have been isolated and characterized by restriction endonuclease cleavage analysis and by the hybridization experiments. The results obtained allow the precise localization of the human fragments inside the beta like globin gene cluster (6). The comparison of the thalassaemic fragments with the normal DNA (6 - 7) shows two different restriction endonuclease sites, for Xba I and Eco RI respectively, downstream from the human beta globin gene.
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PMID:[Construction of a genome library from a beta-0-thalassemic individual from Ferrara: characterization of clones containing beta globin genes]. 630 96


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