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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High fetal haemoglobin levels of 5-15% are present in adult heterozygotes for delta beta-thalassaemia as the result of large deletions of DNA. We have cloned DNA spanning the deletion breakpoint for a new Indian delta beta-thalassaemia associated with mild anaemia. The 5' breakpoint is at 42151 of GenBank file HUMHBB, which is about 1 kb 3' of the A gamma globin gene poly A site at 41003. On the 3' side of the breakpoint, the sequence is homologous to L1 (KpnI) repetitive DNA located 3.6-10 kb 3' of the beta-globin gene: Indian delta beta-thalassaemia DNA is 74% homologous to the inverted complement of HUMHBB from 69849 to 70020, followed by a region 78% homologous to the direct sequence of HUMHBB from 70534 to 71010. The precise location of the 3' endpoint of this deletion has not been determined, but it is within L1 sequences located more than 10 kb 3' of the beta-globin gene.
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PMID:The DNA deletion in an Indian delta beta-thalassaemia begins one kilobase from the A gamma globin gene and ends in an L1 repetitive sequence. 260 24

Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the endogenous mouse alpha-globin genes. Transgenic fetuses with high-copy numbers of the transgene suffer severe anemia and die before birth. Using a construct with both the human alpha- and beta-globin genes and the beta-globin DCR, live mice with low-copy numbers were obtained. Both human globin genes are expressed at high levels in adult red cells to give human hemoglobin HbA in amounts equal to or greater than endogenous mouse hemoglobin. Expression of HbA in murine red cells is not accompanied by any increase in mean corpuscular volume (MCV) or mean corpuscular hemoglobin concentration (MCHC). However, these transgenic mice tend to have an increased number of reticulocytes in peripheral blood; consistent with some degree of hemolysis. Metabolic labeling experiments showed balanced mouse globin synthesis, but imbalanced human globin synthesis, with an alpha/beta biosynthetic ratio of approximately 0.6. Thus, these mice have mild anemia. These results are discussed with relation to the coordinate regulation of alpha- and beta-globin synthesis in erythroid tissues.
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PMID:High-level, erythroid-specific expression of the human alpha-globin gene in transgenic mice and the production of human hemoglobin in murine erythrocytes. 261 6

Bacteriophage T4 DNA ligase effectively joins two adjacent, short synthetic oligodeoxyribonucleotides (oligos), as guided by complementary oligo, plasmid and genomic DNA templates. When a single bp mismatch exists at either side of the ligation junction, the efficiency of the enzyme to ligate the two oligos decreases. Mismatch ligation is approximately five-fold greater if the mismatch occurs at the 3' side rather than at the 5' side of the junction. During mismatch ligation the 5' adenylate of the 3' oligo accumulates in the reaction. The level of the adenylate formation correlates closely with the level of the mismatch ligation. Both mismatch ligation and adenylate formation are suppressed at elevated temperatures and in the presence of 200 mM NaCl or 2-5 mM spermidine. The apparent Km for the oligo template in the absence of salt is 0.05 microM, whereas the Km increases to 0.2 microM in the presence of 200 mM of NaCl. In this report, we demonstrate these properties of T4 DNA ligase for oligo pairs complementary to the beta-globin gene at the sequence surrounding the single bp mutation responsible for sickle-cell anemia. Because of the highly specific nature of the nick-closing reaction, ligation of short oligos with DNA ligase can be used to distinguish two DNA templates differing by a single nucleotide.
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PMID:Specificity of the nick-closing activity of bacteriophage T4 DNA ligase. 275 55

A strategy for using multiple linked markers for genetic counseling is to test sequentially individual markers until a diagnosis can be made. We show that in order to minimize the number of tests performed per case while diagnosing all informative cases the order in which the markers are to be tested is critical. We describe an algorithm to obtain this order using the parameter "I," the frequency of informative cases. The I value for a specific locus used depends on the marker frequency, association with the disease locus, and also on the informativeness of the marker loci already tested. Realizing that a direct assay for the beta S gene already exists, and that most cases of beta-thalassemia in Mediterraneans can be directly diagnosed using synthetic oligonucleotide probes, we illustrate the above technique by examining nine DNA polymorphisms in the human beta-globin cluster for their ability to diagnose sickle-cell anemia in American blacks and beta-thalassemia in Mediterraneans. This analysis shows that 95.39% of all sickle-cell pregnancies can be diagnosed by testing a subset of only six markers chosen by our algorithm. Furthermore, six markers can also diagnose 88.03% of beta-thalassemia in Greeks and 83.56% of beta-thalassemia in Italians. The test set is different from that suggested by the individual informative frequencies due to nonrandom associations between the restriction sites.
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PMID:A strategy for using multiple linked markers for genetic counseling. 299 37

A rapid method of gene detection has been developed utilising DNA fragments immobilized on resins and a sandwich hybridization assay. This method permits the detection of restriction fragment length polymorphisms (RFLPs) without the need to immobilize sample DNA. The method is based on the use of two non-overlapping DNA restriction fragments, one of which is attached to a resin (fragment A) and the other 32P-labelled (fragment B). Fragments A and B will not hybridize to each other unless there is a DNA or RNA fragment capable of hybridizing to both A and B present in the same reaction. Hybridization in this instance will result in the resin being radioactively labelled. The RFLP associated with the mutation causing sickle-cell anaemia was used as a model to develop the method. The resin Sephacryl S-500 appeared most suited to our method for two reasons: (i) DNA immobilization experiments using two coupling procedures and four resins indicated that Sephacryl S-500 bound the most DNA with very little non-covalent coupling. (ii) Hybridization experiments with DNA bound to a number of resins showed that DNA bound to Sephacryl S-500 hybridized most efficiently with a low level of nonspecific hybridization. Using optimum hybridization conditions 5 X 10(-18) mol of beta-globin DNA could be detected. The method has been used to distinguish between DNA from sickle, heterozygote and normal patients.
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PMID:A rapid method of gene detection using DNA bound to Sephacryl. 300 Aug 72

Hemoglobin Pasadena [beta 75(E19)Leu----Arg] was found in a boy who had an acute episode of anemia and rapid splenic enlargement. His father was the only other member of a large family with this hemoglobinopathy. We have used gene mapping techniques for direct identification of the beta-globin gene mutation. To correlate the DNA findings with the structural identification of this variant, we have also performed globin chain separation and analysis of the tryptic peptides using high performance liquid chromatography and secondary ion mass spectral analysis.
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PMID:Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes. 334 4

Goats and some sheep synthesize a juvenile hemoglobin, Hb C (alpha 2 beta C2), at birth and produce this hemoglobin exclusively during severe anemia. Sheep that synthesize this juvenile hemoglobin are of the A haplotype. Other sheep, belonging to a separate group, the B haplotype, do not synthesize hemoglobin C and during anemia continue to produce their adult hemoglobin. To understand the basis for this difference we have determined the structural organization of the beta-globin locus of B-type sheep by constructing and isolating overlapping genomic clones. These clones have allowed us to establish the linkage map 5' epsilon I-epsilon II-psi beta I-beta B-epsilon III-epsilon IV-psi beta II-beta F3' in this haplotype. Thus, B sheep lack four genes, including the BC gene, and have only eight genes, compared with the 12 found in the goat globin locus. The goat beta-globin locus is as follows: 5' epsilon I-epsilon II-psi beta X-beta C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta Y-beta F3'. Southern blot analysis of A-type sheep reveals that these animals have a beta-globin locus similar to that of goat, i.e., 12 globin genes. Thus, the beta-globin locus of B-haplotype sheep resembles that of cows and may have retained the duplicated locus of the ancestor of cows and sheep. Alternatively, the B-sheep locus arrangement may be the result of a deletion of a four-gene set from the triplicated locus.
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PMID:Structural organization of the beta-globin locus of B-haplotype sheep. 336 82

Hb Mississippi was discovered in a 6-year-old Chinese girl with chronic anemia and thalassemia intermedia. Family studies revealed that she had inherited the Hb Mississippi from her father as well as inheriting a gene for beta+-thalassemia from her mother. Electrophoretic analyses of the hemolysate of the father of the father and the proband on polyacrylamide gels at pH 8.6 showed that the abnormal hemoglobin had three distinct mobilities. A similar pattern was also observed by isoelectricfocusing. In addition, multiple abnormal peaks were observed by high performance liquid chromatographic hemoglobin separations as well as high performance liquid chromatographic globin chain separation. Structural analysis of the abnormal hemoglobin demonstrated a single abnormality; the substitution of serine to cysteine at position 44 (CD3) of the beta-globin chain. Since CD3 is on the surface of the beta-globin chain, it was thought that polymerization of the abnormal hemoglobin by disulfide linkages might have been responsible for the anomalous behavior on electrophoresis and high performance liquid chromatography. Gel filtration chromatography on G-200 Sephadex confirmed this supposition and demonstrated that the abnormal globin chain polymerized with itself as well as with other globin chains.
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PMID:Hb Mississippi [beta 44(CD3)Ser----Arg]: a new variant with anomalous properties. 342 43

A murine beta-thalassemia was corrected by the transfer of cloned beta-globin genes into the mouse germ line. The cloned mouse beta maj-globin gene or the cloned human beta-globin gene was introduced into mice deficient in beta-globin synthesis because of a deletion of the beta maj-globin gene. Both introduced genes produced functional beta-globin chains, leading to a reduction in one case, and elimination in another case, of the anemia and associated abnormalities of the red blood cells.
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PMID:Correction of murine beta-thalassemia by gene transfer into the germ line. 346 64

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.
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PMID:Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis. 375 67


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