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

A study of the molecular pathology of beta thalassaemia in the Asian Indian immigrant population in the U.K. included 37 patients with thalassaemia major and 14 with thalassaemia intermedia. Using a combination of oligonucleotide probe hybridization and restriction endonuclease analysis the mutations in 100/102 (98%) of the beta thalassaemia genes were characterized. Nine different types were found, of which six are associated with beta zero, one with severe beta+ and two with mild beta+ thalassaemia. Comparison of the beta-globin gene cluster haplotypes, alpha globin genotypes and beta gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co-inheritance of a high Hb F determinant associated with the - + - + + 5' beta haplotype and the inheritance of a mild beta-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians. In comparison with other population groups. beta thalassaemia in Asian Indians is not associated with one or two predominant mutations. Despite this, prenatal diagnosis by direct detection is possible in the majority of families by restriction analysis and a limited number of oligonucleotide probes since the majority of severely affected individuals are homozygous for a single mutation. The characterization of these mutations should be useful for the planning of prenatal diagnosis programmes for beta thalassaemia in other Asian Indian communities.
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PMID:The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis. 290 65

Alpha thalassemia is rarely diagnosed in Australian families of British or Northern European ancestry. In 1972, a third generation Australian was shown to have alpha thalassemia. In the absence of known Mediterranean or South East Asian ancestry it was reported as being the first example of alpha thalassemia in an Australian family. Further study of the proposita in 1985 using DNA mapping of the alpha globin gene complex, shows a distinctive molecular defect identical to the British type of alpha thalassemia. The latter is clearly different from the commonly encountered Mediterranean and South East Asian alpha zero haplotypes. Recognition that alpha zero thalassemia occurs in Australians is important since it may produce a microcytic hypochromic anemia. Its inheritance together with other forms of alpha thalassemia may lead to severe Hb H disease or Hb Bart's hydrops fetalis.
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PMID:Alpha thalassemia British type (alpha alpha/--Brit) in an Australian family. 302 Apr 89

Detailed restriction enzyme analysis of the DNA from a Chinese female showed that one of her chromosomes had a greater than 17.5 kb deletion of DNA, including the psi alpha, alpha 2, and alpha 1 globin genes, which is present in many Southeast Asians with an alpha-thalassemia-1 chromosome. Her "normal" chromosome had the expected cluster of alpha-like globin genes (5'-zeta-psi zeta-psi alpha-alpha 2-alpha 1-3'), but the segment of DNA between the two alpha globin genes was elongated by some 0.5-0.7 kb. Analyses of various restriction sites suggested that this normal variant of the human alpha globin gene complex is due to a crossover between a normal chromosome with (alpha alpha) and a chromosome with an alpha-thalassemia-2 (-alpha 3.7) and an -alpha 2 alpha 1-hybrid gene.
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PMID:An elongated segment of DNA observed between two human alpha globin genes. 302 76

The human adult alpha globin genes, alpha 2 and alpha 1, are contained within two tandemly arranged duplication units. Each unit spans 4 kb of DNA, and contains three homology blocks (X, Y, Z) separated by non-homologous sequences. Segmental DNA recombination processes between the two units have resulted in high frequencies of two types of deletions in certain human populations, each deletion removing one alpha globin gene from chromosome 16, (alpha-thalassemia 2). In order to study the molecular mechanisms of alpha-thalassemia 2, and of homologous DNA recombination in general in mammalian cells, we have reconstructed these two alpha-thalassemia 2 genotypes in monkey cells. The two duplication units have been cloned in an SV40 origin-containing vector, and transfected into COS 7 cells. Newly replicated plasmid DNA was isolated and analyzed by Southern blot hybridization. Homologous DNA recombination occurs with high frequencies (10-20% per kb of homology), and this generates both types of alpha-thalassemia 2 deletions on the episomes in the monkey cells. Removal of the 5' end of either one, or both, of the X blocks prior to DNA transfection affects the relative frequencies of the two alpha-thalassemia 2 genotypes in a novel way. We consider and discuss these results in terms of several alternative models. Our data suggest the existence of hot spot(s) for initiation of homologous DNA recombination, or recombination promoting element(s), in a specific region of the human adult alpha globin locus. A DNA sequence that defines the boundaries of the two duplication units, and has been implicated in the initiation of gene conversion of the two X blocks, is contained within this region.
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PMID:Reconstruction of human alpha thalassemia-2 genotypes in monkey cells. 303 16

Human alpha-thalassemia-2 genotype -alpha 4.2 is the result of meiotic recombination between two 1.3 kb long, homologous DNA segments, X(alpha 2) and X(alpha 1), located in the adult alpha globin locus. The two segments can also undergo intramolecular recombination on extrachromosomal vectors transfected into mitotically dividing primate cells (COS 7). The existence of a gradient of sequence divergence between X(alpha 2) and X(alpha 1) makes them an interesting system to study the relationship between efficiencies of homologous DNA recombination and the extent of dispersed and localized base mismatches. By partial restriction mapping and DNA sequencing of plasmids recombined in COS 7 cells and rescued from bacteria HB 101, we have determined the distribution of recombinational resolution sites along the two X blocks. Most, if not all, of the homologous recombination events between the two X blocks appear to be single crossing-over without efficient gene correction or repair of base mismatches. The distribution of the sites of recombinational resolution is inversely correlated with that of the gradient of sequence divergence, with only approximately 7% of the X recombinants resolved within the 3' third of the X blocks where two diverged Alu family repeats reside. The Alu sequence within which one of the X recombinants resolved is homologous to a previously characterized alpha thalassemia deletion point.
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PMID:Recombinational resolution in primate cells of two homologous human DNA segments with a gradient of sequence divergence. 314 5

We describe here the screening of a small group of apparently healthy individuals belonging to the tribal communities of Koya Dora and Konda Reddi. A remarkably high incidence of deletion and nondeletion alpha + thalassemia mutants has been found with allele frequencies and distributions characteristic to each tribe. We have confirmed the strict relationship between Hb S levels and the number of alpha globin genes in double heterozygotes for the S gene and alpha thalassemia. In this population sample we did not find either heterozygous carriers of alpha 0 thalassemia (deletion of both alpha genes in "cis") or individuals showing hemolytic anemia due to inactivation of three alpha-globin genes (Hb H disease). Selection by malaria is most probably responsible for the prevalence of the various alpha + thalassemia haplotypes among the two tribal populations of Andhra Pradesh.
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PMID:Prevalence and molecular heterogeneity of alfa+ thalassemia in two tribal populations from Andhra Pradesh, India. 316 39

The effects of alpha thalassaemia on sickle cell-beta zero thalassaemia have been studied by comparing haematological and clinical features in four subjects homozygous for alpha thalassaemia 2 (2-gene group), 27 heterozygotes (3-gene group), and 55 with a normal alpha globin gene complement (4-gene group). Alpha thalassaemia was associated with significantly higher haemoglobin levels and lower reticulocyte counts independent of the presence of splenomegaly. Contrary to expectation, alpha thalassaemia was associated with small but significant increases in mean cell volume and mean corpuscular haemoglobin concentration. Splenomegaly at age 5 years and episodes of acute splenic sequestration were significantly more frequent in the 4-gene group. There were no significant differences in painful crises, acute chest syndrome, or other clinical features.
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PMID:The interaction of alpha thalassaemia and sickle cell-beta zero thalassaemia. 321 94

A female child with alpha thalassaemia trait, moderate mental retardation, and dysmorphic features has inherited an abnormal chromosome 16 complement as a result of the unbalanced segregation of a maternal balanced translocation. Cytogenetic analysis indicates that the patient is monosomic for 16p13.3----pter and trisomic for 10q26.13----qter. DNA studies show that the patient has not inherited either maternal alpha globin allele. This accounts for the alpha thalassaemia trait in the child and places the human alpha globin complex in band 16p13.3----pter.
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PMID:Localisation of human alpha globin to 16p13.3----pter. 323 67

In this paper we report that the combination of a triplicated alpha globin locus with heterozygous beta-thalassaemia produces a clinical phenotype of thalassaemia intermedia in five Italian subjects from four unrelated families, while in two other cases the phenotype was thalassaemia minor. The haematological findings of the five patients were uniform, producing a benign form of thalassaemia intermedia, transfusion independent, with a long life expectancy. The pattern of inheritance of the two genetic determinants and the more pronounced beta/alpha globin chain imbalance, demonstrates that the genetic combination is indeed the cause of the phenotype. The pattern of restriction enzyme site polymorphisms suggests the presence of the beta IVS I 110 G----A mutation at least in three of these cases.
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PMID:A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia. 359 44

Ferrokinetic studies, alpha globin gene mapping, and assessment of iron status have been carried out in 16 healthy subjects with heterozygous beta thalassaemia. Six subjects had coinherited alpha thalassaemia and had more balanced alpha/beta globin chain synthesis ratios than the remaining 10 subjects with uncomplicated heterozygous beta thalassaemia. The overall efficiency of erythropoiesis was significantly reduced in the latter group (mean 76 +/- 17 (SD)% of normal), but was indistinguishable from normal in subjects with coexistent alpha thalassaemia. Red cell survival was unimpaired in both groups, indicating that the defect was one of mild ineffective erythropoiesis rather than peripheral haemolysis. Values for total plasma iron turnover were normal or only slightly increased. This suggests a lack of any additional stimulus to erythropoiesis, which might normally be expected to compensate easily for the mild degree of anaemia. Uncomplicated heterozygous beta thalassaemia produces an extremely mild disorder of erythropoiesis, which is dependent on the imbalance between alpha and beta globin chain synthesis, and is not associated with a risk of serious iron overload.
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PMID:Erythrokinetics and iron status in heterozygous beta thalassaemia, and the effect of interaction with alpha thalassaemia. 359 48


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