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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies in two Jamaican Negro families, including haematological and haemoglobin analysis, haemoglobin synthesis, and globin messenger-RNA assay, have defined two alpha-thalassaemia phenotypes which resemble the severe (alpha-thalassaemia 1) and mild (alpha-thalassaemia 2) forms of the disorder described in Orientals. Genetic analysis suggests that subjects with the alpha-thalassaemia-1 phenotype are homozygous for the alpha-thalassaemia-2 determinant. Restriction-endonuclease mapping shows that alpha-thalassaemia-2 results from the deletion of one of the linked pair of alpha-chain genes. Hence the genotypes of the alpha-thalassaemia heterozygotes and homozygotes in these families are -alpha/alpha alpha and -alpha/-alpha respectively. If these are the usual alpha-thalassaemia genotypes in Negroes, these findings explain the difference in clinical expression of the disorder between Orientals and Negroes--in particular, the absence of haemoglobin Bart's hydrops and the rarity of haemoglobin-H disease in Negroes.
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PMID:Negro alpha-thalassaemia is caused by deletion of a single alpha-globin gene. 8 8

The organization of alpha globin genes in normal human DNA was examined by restriction endonuclease mapping, alpha globin-specific fragments in endonuclease digests of total cell DNA were identified after electrophoresis by hybridization with [32P]cDNA following the blotting procedure of Southern [(1975) J. Mol. Biol. 98, 503--517]. The data provide direct evidence for the duplication of alpha genes and further indicate that these loci are closely linked within a single restriction fragment. The HindIII sites (codons 90/91) of these duplicated genes lie approximately 3.7 kilobases apart in the physical map proposed for this region. This organization of alpha genes can be altered in DNA of individuals with alpha-thalassemia.
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PMID:The duplicated human alpha globin genes lie close together in cellular DNA. 28 16

We have used restriction endonuclease mapping of cell DNA to investigate the structure of the beta-globin gene in beta-thalassemias. Among 17 individuals with beta +- and beta 0-thalassemia, we observed three patients of Indian origin with beta 0-thalassemia whose DNA revealed a consistent mapping abnormality. In one beta allele in each diploid cell, 0.6 kilobase of DNA was deleted from beta-specific Pst I and Bgl II restriction fragments. This deletion involved 3' beta-globin gene sequences and eliminated the EcoRI site normally present at codons 121/122, but it did not extend to the BamHI site at codons 98--100 on the 5' side of the 0.90-kilobase intervening sequence normally present in beta-globin genes. Partial beta-globin gene deletion appears, therefore, to be a primary molecular defect seen in certain patients with beta 0-thalassemia.
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PMID:Partial deletion of beta-globin gene DNA in certain patients with beta 0-thalassemia. 28 80

The alpha-thalassemia syndromes are a group of inherited anemias, the clinical severity of which has been shown to increase with the number of alpha-globin structural genes deleted. Employing restriction endonuclease gene mapping, we defined the organization of the alpha-globin genes in cellular DNA from Chinese subjects with various alpha-thalassemia syndromes. The four alpha-globin genes of normals are at two loci located on a 23.0-kilobase pair (kb) Eco RI fragment. In deletion type hemoglobin-H disease the 5' alpha-globin locus is deleted and the single 3' alpha-globin locus is found on a 19.0-kb Eco RI fragment. In alpha-thalassemia-2 there are two alpha-globin genes on a 23.0-kb Eco RI fragment and one on a 19.0-kb fragment. In alpha-thalassemia-1 and the nondeletion type of hemoglobin-H disease the two alpha-globin genes are at two loci on one chromosome and none reside on the other chromosome.
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PMID:Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes. 44 45

Deletions in the DNA of individuals with hereditary persistence of fetal haemoglobin (HPFH) and 8 beta-thalassaemia have been mapped as a means of identifying regulatory sequences involved in the switch from fetal to adult globin gene expression. The end points of these deletions have been precisely located with respect to restriction endonuclease cleavage sites within and surrounding the gamma-, delta- and beta-globin genes in normal human DNA and the deletion maps were used to obtain definitive evidence for the physical linkage of the fetal and adult beta-like globin genes in the order 5'Ggamma-Agamma-delta-beta 3'. Correlation of haematological data and the location of deletions in two cases of HPFH and one case of deltabeta-thalassaemia suggest that a region of DNA located near the 5'-end of the delta-globin gene may be involved in the suppression in cis of gamma-globin gene expression in adults. The interpretation of a second case of deltabeta-thalassaemia is complicated by the fact that the deletion removes the Agamma-gene in addition to the region near the 5'-end of the delta-globin gene.
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PMID:Characterisation of deletions which affect the expression of fetal globin genes in man. 45 Jan 9

Study of Asians has previously indicated that deletion of alpha-globin structural genes is the predominant lesion in alpha-thalassemias and that Hb H disease occurs when three of four normal alpha loci per cell are deleted. To test the generality of this model, Hb H disease DNAs of both Asian and non-Asian origin were analyzed by restriction endonuclease mapping using the technique of Southern (1975). Whereas in normal DNA, alpha sequences are present in a single Eco Rl fragment of cellular DNA approximately 22.5 kb long, fragments of 22.5, 20 and 2.6 kb were found in various Hb H disease DNAs. The 20 kb Eco Rl fragment alone, in which a single alpha-globin structural locus resides, was found in Asian Hb H disease DNA. This finding is consistent with the deletion model of alpha-thalassemia. In contrast, seven of eight non-Asian Hb H disease DNAs displayed a more complex molecular composition. The fragment patterns observed were 22.5 kb alone, 22.5 plus 2.6 kb, 20 plus 2.6 kb and 20 kb alone. Non-Asian Hb H disease DNAs contained one, two or three alpha loci per cell in contrast to the one locus predicted by the simple deletion model of alpha-thalassemia. The data are best explained by the existence of defective alpha loci in certain individuals with alpha-thalassemia, particularly outside the Asian population. Restriction mapping of the 20 kb Eco Rl fragment found in Asian and some non-Asian Hb H disease DNAs demonstrated a striking similarity in the placement of restriction sites about the single alpha gene compared with sites about the two genes in the 22.5 kb Eco Rl fragment seen in normal DNA. These data are consistent with origin of the 20 kb fragment from the 22.5 kb normal Eco Rl fragment by either unequal crossing-over or a deletion event. The molecular heterogeneity and frequent occurrence of defective alpha loci in non-Asian Hb H disease DNAs described here may explain, in part, the clinical heterogeneity of alpha-thalassemias and the absence of the homozygous deletion state (hydrops fetalis) in non-Asians. Further study of cellular DNA fragments containing the defective alpha loci identified in this work may indicate the types of specific mutations responsible for abnormal globin gene expression and complement similar studies on abnormal beta genes in beta-thalassemias.
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PMID:The molecular basis of alpha-thalassemias: frequent occurrence of dysfunctional alpha loci among non-Asians with Hb H disease. 45 60

Twenty-one cases of beta 0 and beta +-thalassaemia have been analysed by restriction endonuclease mapping. In most cases no deletion in the regions surrounding the beta- and delta-globin genes could be detected. However, in a single Asian case of beta 0-thalassaemia, homozygous clinically, one of the homologous chromosomes contained a beta-globin gene with a deletion of 600 base pairs of DNA and comprising most or all of the 3' end of the structural gene including the EcoRI restriction site within the beta-globin coding sequence.
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PMID:The structure of the human beta-globin gene in beta-thalassaemia. 46 Dec 3

We have constructed a physical map of restriction endonuclease cleavage sites in the (delta (+) beta)-globin gene region in the DNA of patients with (delta beta(0))-thalassaemia. This map shows that a 10 kb deletion has occured in (delta beta (0))-thalassaemia to remove the entire beta-globin gene and the 3' portion of the delta-globin gene. The 5' terminus of the deletion is in the large intron of the delta-globin gene and the 3' terminus 1.8 kb to the 3'-side of the beta-globin gene. A similar deletion of about 7 kb has been described previously in the DNA of patients with Hb Lepore; the 5' terminus of the deletion is also in the delta-globin gene but the 3' terminus is in the beta-globin gene. Comparison of the foetal (gamma) globin gene expression in adults with (delta beta(0))-thalassaemia and Hba Lepore suggests that the 3' extragenic regions of the beta-globin gene contain DNA sequences involved in the regulation of gamma-globulin gene expression.
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PMID:Physical mapping of the globin gene deletion in (delta beta (0)) -thalassaemia. 47 2

Two Chinese patients with HbQ-alpha 2 74 Asp replaced by His beta 2-alpha-thalassemia, one HbQ-alpha 2 74 or 75 Asp replaced by His beta 2 carrier, and one HbG-alpha 2 30 Glu replaced by Gln beta 2 carrier were studied to determine the number of alpha-globin genes in their chromosomes. DNA was isolated from white blood cells and bone marrow cells and studied by liquid hybridization and by hybridization of DNA fragments obtained by restriction enzyme endonuclease digestion (Ecr to nitrocellulose filters. The liquid hybridization analysis showed that in HbQ-alpha 2 74 Asp replaced by His beta 2-alpha-thalassemia, as in HbH disease, only one-fourth of the usual number of alpha-globin genes is present. Hybridization patterns of DNA restriction enzyme fragments showed that in HbQ-alpha 2 74 Asp replaced by His beta 2-alpha-thalassemia one chromosome has both alpha-globin genes deleted and the other chromosome, which carries the alpha-mutant gene, has one alpha-globin gene deleted. Our results show that the HbQ-alpha 74 Asp replaced by His structural gene is located adjacent to a deleted alpha-globin gene, whereas the alpha-globin gene adjacent to HbG-alpha 30 Glu replaced by Gln gene is not deleted.
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PMID:The alpha-globin gene adjacent to the gene for HbQ-alpha 74 Asp replaced by His is deleted, but not that adjacent to the gene for HbG-alpha 30 Glu replaced by Gln; three-fourths of the alpha-globin genes are deleted in HbQ-alpha-thalassemia. 50 45

We investigated the molecular basis of hemoglobin-H disease by hybridization and restriction endonuclease mapping of the DNA in the Mediterranean populations. Of the 12 patients studied from Cyprus and Sardinia, 8 had the typical deletion defect with a single remaining alpha-globin gene. The nondeletion type of alpha-thalassemia was found in 3, and a "dysfunctional" gene in one. We conclude that the predominant cause of alpha-thalassemia in these populations is gene deletion.
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PMID:Molecular basis of hemoglobin-H disease in the Mediterranean population. 50 46


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