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Biomedical subjects

J B Clegg

Publications and source records attributed to J B Clegg.

At least 127 records · Page 7Linked to original sources
PubMed1982

Simultaneous expression of globin genes for embryonic and adult hemoglobins during mammalian ontogeny.

The dominant hemoglobin of the adult hamster was detected in yolk-sac erythroid cells, and its identity was confirmed by peptide mapping and by analysis of relevant peptides. Both the presence and active synthesis of two embryonic hemoglobins presumed to exist only in yolk-sac erythroid cells were detected in neonatal liver and spleen. Thus the time span of expression of both embryonic and adult globin genes during mammalian ontogeny may be considerably broader than presently believed.

Age Factors↗
PubMed1982

Multiple arrangements of the human embryonic zeta globin genes.

Rearrangements which are most readily explained by homologous crossover between misaligned segments of DNA in the region of the human embryonic zeta (zeta) globin genes have been identified in individuals of three different racial origins. These recombination events have resulted in a surprisingly high prevalence of chromosomes with single (0.4%) and triplicated (1.3%) zeta genes with apparently no significant effect on the phenotype.

Chromosomes, Human, 16-18↗
PubMed1982

The interaction of alpha-thalassemia and homozygous sickle-cell disease.

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (alpha-/alpha-), may be heterozygous for alpha-thalassemia 2 (alpha-/alpha alpha), or may have a normal alpha-globin-gene complement (alpha alpha/alpha alpha). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin A2, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled cell counts, and serum total bilirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (alpha-/alpha alpha) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in other two subgroups. These data confirm previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.

Adolescent↗
PubMed1982

Linkage analysis of nondeletion hereditary persistence of fetal hemoglobin.

Nondeletion forms of hereditary persistence of fetal hemoglobin may result from regulatory disorders of globin gene expression. The defects in two such conditions were localized by demonstrating a tight genetic linkage between the disorders and polymorphic restriction endonuclease sites within the beta-like globin gene complex. In one instance, the defect probably occurred outside the region of DNA between the epsilon- and beta-globin genes.

Chromosome Deletion↗
PubMed1982

The British type of non-deletion HPFH: characterization of developmental changes in vivo and erythroid growth in vitro.

Further studies of a unique British family with a rare type of hereditary persistence of fetal haemoglobin (HPFH) have confirmed that this condition appears to result from a regulatory defect affecting globin gene expression. Adult heterozygotes for this disorder have 3.5-10.0% Hb F while homozygotes have 18-21% Hb F and in both cases the Hb F contained predominantly A gamma chains (89-94%). In all other respects these individuals were haematologically normal. Two obligate heterozygotes were studied from birth, at which time both the proportion of Hb F and the G gamma/A gamma ratio were completely normal. There was a delayed decline in Hb F which continued well into childhood and a parallel decline in the proportion of G gamma chains. The growth of erythroid bursts showed no difference in number, size or erythropoietin responsiveness between homozygous HPFH, heterozygous HPFH or normal family members. Haemoglobin synthesis in these bursts showed the normal pattern of asynchrony between gamma and beta chain synthesis but there was an overall increase in gamma chain production in the HPFH cases, particularly the homozygotes, compared to normal. In addition, the abnormal G gamma/A gamma ratio was faithfully reproduced in vitro. This condition appears to result, therefore, from a regulatory abnormality affecting the postnatal repression of gamma chain synthesis.

Adolescent↗
PubMed1982

Restriction endonuclease maps of the beta-like globin gene cluster in the British and Greek forms of HPFH, and for one example of G gamma beta + HPFH.

We report here restriction endonuclease maps of the beta-like globin gene cluster for the British form of HPFH and for a case of G gamma beta + HPFH, and also confirm and extend previous reports of the map for the Greek form of HPFH. These results show that all these conditions belong to a group lacking any substantial deletion or rearrangement of DNA sequence in this gene cluster. The absence of any gross disruption of the structure of this region of the genome, together with evidence that the HPFH genotype is either allelic with, or closely linked to, the beta-like globin gene cluster, suggests that the responsible lesions are nearer to being purely regulatory in nature than in forms of HPFH due to substantial deletions. Thus these conditions promise to provide less equivocal evidence about the regulation of beta-like globin gene expression than has so far been available.

Chromosome Mapping↗
PubMed1982

Haemoglobin Constant Spring has an unstable alpha chain messenger RNA.

Haemoglobin Constant Spring (Hb CS) is a variant with an elongated alpha-chain associated with an alpha + thalassaemia phenotype. The amount of alpha mRNA relative to beta mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of alpha + thalassaemia. In a patient with Hb CS-H disease there was greater alpha/beta mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the alpha mRNA in the patient's peripheral blood was derived from the alpha 1 (alpha A) gene. The data suggest that alpha CS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3' non-coding region during translation.

Female↗
PubMed1982

The molecular basis for beta o thalassaemia intermedia in an Iranian individual.

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.

Adult↗
PubMed1982

alpha-globin gene deletions associated with Hb J Tongariki.

Three identical alpha + thalassemia genes, one of which always carried the Hb J Tongariki mutation, have been observed in Vanuatuans. Despite the fact that at least two of them have arisen by different types of crossover event, the expression of all three haplotypes is identical.

Chromosome Deletion↗
PubMed1981

A novel rearrangement of the human beta-like globin gene cluster.

The first example of a duplication involving the human beta-like globin genes has been characterised in DNA from a native of Vanuatu. Restriction endonuclease mapping has shown that a 5 kb insert of DNA in the gamma-delta-beta gene cluster is due to duplication of the Ggamma-globin gene and results in a new rearrangement 5'-epsilon-Ggamma-Ggamma-Agamma-delta-beta-3'.

Adult↗
PubMed1981

Restriction mapping of a new deletion responsible for G gamma (delta beta)o thalassemia.

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.

Chromosome Deletion↗
PubMed1981

Highly variable regions of DNA flank the human alpha globin genes.

A series of restriction fragment length polymorphisms which are due to DNA rearrangements have been identified within two highly variable regions flanking the human alpha globin genes. The existence of such highly polymorphic areas provides a large number of individual genetic markers for the alpha globin gene cluster on chromosome 16. If, as seems likely, such regions occur frequently throughout the human genome they should be of considerable value in the antenatal diagnosis of genetic disease.

Chromosomes, Human, 16-18↗
PubMed1981

Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?

Each of three families of northern European origin contains a mentally retarded son with hemoglobin H (Hb H) disease. One parent is a carrier of mild alpha-thalassemia and the other is normal, suggesting that this form of Hb H disease results from the interaction between an inherited defect of alpha-chain production and one member of the pair in chromosome 16 and a new mutation on the other. Restriction-enzyme analysis indicated that the new mutation was not the same in the other three patients, and demonstrated at least two hitherto undescribed lesions involving the alpha-globin gene cluster. Unless the association between the Hb H disease and mental retardation is fortuitous, the new mutations may also be related to the development changes in these children. Since the mutations only came to light because there was concurrent inheritance of an additional alpha-thalassemia determinant, this type of mutation of chromosome 16 may have been overlooked in other mentally retarded patients.

Adult↗