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)

K562 human leukemia cells synthesize embryonic hemoglobins after culture in the presence of hemin. We have rigorously identified these hemoglobins by globin chain analysis and peptide mapping. No adult hemoglobin could be detected, and beta-globin synthesis was less than 2 ppm of total protein synthesis. Persistent embryonic globin gene expression is known to occur as a consequence of globin gene deletions. However, restriction endonuclease mapping showed that the globin gene complexes in K562 cells are indistinguishable from normal. Hemin increased the rate of embryonic globin synthesis. The pattern of hemoglobin synthesis proved to be stable when cells from different laboratories were compared. One line, however, synthesized large amounts of Hb X and very little Hb Portland in response to hemin. Hb X has been previously detected in human embryos; we show here that it has the composition epsilon 2 gamma 2 and is diagnostic of imbalanced chain synthesis or "zeta thalassemia." We have identified several agents that induce hemoglobin synthesis in K562 cells. Different inducers induced different patterns of embryonic hemoglobin synthesis but never any adult hemoglobin synthesis.
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PMID:Embryonic erythroid differentiation in the human leukemic cell line K562. 626 39

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

beta 0-Thalassemia is a heterogeneous group of disorders associated with absence of beta-globin. In a survey of DNAs from patients with beta 0-thalassemia of diverse ethnic origins, a change at the splice junction at the 5' end of the large intervening sequence (IVS 2) of the human beta-globin gene has been found in one patient of Italian and another two of Iranian ethnic origins. The enzyme Hph I recognizes a change at this site and generates a large-than-normal fragment of DNA, which hybridizes specifically to a beta-globin IVS 2 probe. No other changes in beta-globin gene DNA structure or organization are detectable by extensive restriction endonuclease analysis. The enzyme HinfI which recognizes a sequence beginning three nucleotides from the 5' end of the IVS 2 splice junction, produces normal fragments and localizes the defect to a G-G-T sequence at the 5'-end IVS 2 splice junction. This sequence is known to be remarkably conserved in all globin genes from many species and in most other genes examined to date. Thus, in at least some beta 0-thalassemia patients, the beta 0-thalassemia defect is associated with a nucleotide change at a splice junction. These patients provide unique examples of naturally occurring defects in splice junctions of eukaryotic genes associated with absence of specific gene function.
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PMID:A nucleotide change at a splice junction in the human beta-globin gene is associated with beta 0-thalassemia. 627 Jun 63

Restriction endonuclease mapping of nondeletion alpha-thalassemia determinants from a variety of racial groups showed no detectable abnormalities within a 40-kilobase region of the zeta-alpha globin gene cluster. By using a zeta-specific probe, we defined three different types of interactions that give rise to Hb H disease, each involving a nondeletion alpha-thalassemia haplotype. mRNA analysis showed further diversity within these groups, indicating that there are at least three nondeletion determinations.
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PMID:Genetic and molecular diversity in nondeletion Hb H disease. 627 19

DNA from individuals heterozygous for (G)gamma(deltabeta)(o) thalassaemia has been studied by restriction endonuclease analysis. The results reveal a new molecular defect associated with this condition. A total of three defects is now responsible for the one single phenotype, thereby emphasising the complex relationship between genotype and phenotype among the disorders of beta-like globin synthesis in man.
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PMID:Restriction mapping of a new deletion responsible for G gamma (delta beta)o thalassemia. 627 49

Enzymes which fragment DNA at specific sites have been used to prenatally detect sickle cell anemia, alpha-thalassemia, and beta-thalassemia from amniotic fluid aspirates. Within the last few years, the use of combined restriction endonuclease systems (EcoRI and HindIII) for the antenatal detection of sickle cell anemia was found to provide an exact diagnosis of sickle cell status in 80% of couples at risk. Similar systems have been developed for homozygous alpha- and beta-thalassemia. Clinical applications of this technique and future implications are discussed.
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PMID:The use of restriction endonucleases in the prenatal diagnosis of hemoglobinopathies. 628 41

Hemoglobin A2 levels in normal adults are rarely greater than 3.5%. In patients heterozygous for beta-thalassemia, they average about 5% but do not usually exceed 7%. We studied a family in which four patients with heterozygous beta-thalassemia had HbA2 levels of 8.4% to 11.2%. Globin biosynthesis studies and restriction endonuclease mapping of the alpha-globin loci showed homozygous or heterozygous alpha-thalassemia-2 as well as beta-thalassemia in some family members. The delta- and beta-globin genes were examined by using the restriction enzymes Eco RI, Pvu II, and Xba I, which cut both within and outside the coding portions of the delta- and beta-loci. Only the expected delta- and beta-globin gene containing fragments were present, excluding a crossover event producing a fusion gene that would code for delta-globin but possibly be under the regulatory influence of nucleotide sequences that control the expression of the beta-gene. This kindred provides evidence that in the presence of beta-thalassemia, expression of the delta-gene, beyond that commonly seen, is possible. This could be a direct result of the gene defect producing beta-thalassemia or be due to differences in the delta-globin gene linked to this beta-thalassemia gene. The interactions of alpha- and beta-thalassemia may alter tetramer assembly and increase HbA2 levels; however, this possibility seems less likely.
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PMID:Beta-thalassemia with exceptionally high hemoglobin A2. Differential expression of the delta-globin gene in the presence of beta-thalassemia. 628 19

The alpha globin genotypes of 55 beta thalassaemia heterozygotes have been determined by restriction endonuclease analysis to identify those with interacting alpha thalassaemia genes. A comparison of the haematological and haemoglobin synthesis findings of individuals with normal alpha genotypes (alpha alpha/alpha alpha) with those with one (-alpha/alpha alpha) or two (-alpha/-alpha) alpha genes deleted shows that the latter two groups have more balanced globin chain synthesis ratios, higher haemoglobin levels, and larger, better haemoglobinized red cells. This suggests that the degree of globin chain imbalance is a significant factor in determining the red cell characteristics in heterozygous beta thalassaemia. Screening programmes for thalassaemia, based on the detection of low MCVs, could miss cases of the interaction of alpha and beta thalassaemia.
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PMID:The interaction of alpha thalassaemia with heterozygous beta thalassaemia. 628 63

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

A 12-year-old male of Chinese ancestry had life-long hemolytic anemia attributed to alpha-thalassemia. Restriction endonuclease mapping of his DNA revealed that in reality, he had three alpha-globin loci, but he was homozygous for pyruvate kinase deficiency. The new pyruvate kinase variant carried by this patient was characterized and designated PK Fukien.
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PMID:Coexistence of alpha-thalassemia and a new pyruvate kinase variant: PK Fukien. 629 20


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