PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “beta-Globins”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

A specific dimerization of rabbit beta-globin messenger ribonucleic acid.

Rabbit globin mRNA, when layered in low salt on 0.1 M-NaCl/sucrose gradients, separates into two peaks of material. Translation of these two RNA fractions in the wheat-germ cell-free system, hybridization against globin complementary DNA (cDNA) and cross-hybridization against cDNA species prepared from each fraction show that the first peak sedimenting at 10S is a alpha-globin mRNA and the second peak, sedimenting at approx. 15S, is beta-globin mRNA. The sedimentation rate of the beta-globin mRNA is concentration-dependent. By changing concentration and pH, it is indicated that in low-salt beta-globin mRNA adopts a conformation that leads to specific, but weak, self-dimerization during centrifugation in 0.1M-NaCl. This property permits rapid preparation of intact and relatively pure alpha- and beta-globin mRNA species.

Animals↗
PubMed1976

Amplification and characterization of a beta-globin gene synthesized in vitro.

Full-length, double-stranded globin DNA was synthesized in vitro starting from rabbit globin mRNA. Several restriction endonuclease cleavage sites with known recognition sequences were mapped on this DNA as a means of assessing the accuracy of in vitro synthesis. By comparing this map with the nucleotide sequences known or predicted from the amino acid sequences of alpha-and beta-chain rabbit hemoglobin, it was possible to show that the synthetic globin DNA is a faithful copy of beta-globin mRNA. Amplification of the synthetic globin DNA was achieved by inserting the molecule into the plasmid PMB9 using the poly(dA)-(dT) joining procedure, and transforming E. coli with the hybrid DNA. Transformants carrying beta-globin DNA were identified by colony hybridization using purified 125I-beta-mRNA probe. Comparison of the restriction maps of the synthetic and inserted globin DNAs showed that the entire synthetic globin DNA molecule was amplified without sequence rearrangements. Both the synthetic and the cloned DNA include the entire coding sequence of the beta-globin gene plus a substantial portion of the untranslated regions flanking the structural gene.

Base Sequence↗
PubMed1977

Complete nucleotide sequence of the 5' noncoding region of rabbit beta-globin mRNA.

The 5' noncoding region sequence of rabbit beta-globin mRNA has been determined. This region is 53 nucleotides long, not including the A-U-G initiator sequence or m7Gppp "cap" structure. 32P-labeled DNA complementary to the 5' noncoding region was synthesized using reverse transcriptase with the synthetic deoxyoctanucleotide d(G-C-A-C-C-A-T-T) as a "primer". The cDNA produced was then sequenced using a modification of the gel-sequencing technique previously developed for DNA sequencing (G.G. Brownlee and E.M. Cartwright, manuscript in preparation). The sequence obtained was checked by depurination and nearest-neighbor analysis. The known sequence at the 3' end of rabbit 18S ribosomal RNA cannot base-pair extensively with the 5' noncoding region of beta-globin mRNA; however, it does form 6 base pairs around the initiation codon.

Animals↗
PubMed1977

Complete 3' noncoding region sequences of rabbit and human beta-globin messenger RNAs.

The 3' noncoding regions of rabbit and human beta-globin mRNAs, 95 and 134 nucleotides in length, have been sequenced. Furthermore, these and previous studies (Baralle, 1977; Proudfoot, 1976a, 1976b) have established about one half of the 589 nucleotide sequence of rabbit beta-globin mRNA, including all of the noncoding region. These sequence studies took advantage of the plus and minus gel-sequencing procedure originally described by Sanger and Coulson (1975) and recently adapted by G.G. Brownlee and E.M. Cartwright (manuscript in preparation). The human and rabbit 3' noncoding region sequences are extensively homologous, except that the human sequence has an addition of 39 nucleotides as compared with rabbit. This extra sequence may have arisen by gene duplication.

Animals↗
PubMed2026

Long-read Sequences Mapped to a Complete Reference Genome Uncover Uncaptured Structural Variants across the Beta-globin Cluster in Africans with Sickle Cell Disease.

African genomes are marked by extensive complexity in the number and distribution of variants, yet remain under-represented in genetic databases and the human reference genome. This gap in representation limits the broad application of genomic medicine. Sickle cell disease (SCD) - one of the most common monogenic diseases - has its highest prevalence in Africa, and variation in disease severity has consistently been linked to the beta-globin locus, including levels of fetal hemoglobin (HbF). Modulation of HbF is central to current SCD gene therapies; however, the inherent complexity and variation at the locus in African genomes presents a challenge to translating these advances to Africa. Here, we align long-read single molecule sequences (LRS) targeted to the beta-globin region to the hg38 and T2T-CHM13v2 genome references in 40 individuals with SCD, predominantly recruited from three African countries. We demonstrate that the expanded T2T-CHM13v2 reference sequence at this locus reduces Structural Variant (SV) calls by 70% and uncovers uncaptured single nucleotide variants (SNVs). Across the cluster we report 343 SVs and 196 SNVs that have not been previously reported, including in LRS data from the All of Us project. By including African populations from ethnolinguistic groups that have not been previously surveyed we improve variant resolution and bolster evidence for observed variation. Finally, we identify a common ∼4kb insertion locus overlapping the HBB promoter among individuals with high HbF. These results demonstrate the utility of combining a comprehensive reference genome with LRS in African populations to uncover genomic variation at disease-associated loci.

SNV↗
PubMed1976

Nucleotide sequence from the coding region of rabbit beta-globin messenger RNA.

A sequence of 89 nucleotides from rabbit beta-globin mRNA has been determined and is shown to code for residues 107 to 137 of the beta-globin protein. In addition, a sequence heterogeneity has been identified within this 89 nucleotide long sequence which corresponds to a known polymorphic variant of rabbit beta-globin.Images

Animals↗
PubMed1975

Human globin gene analysis for a patient with beta-o/delta beta-thalassemia.

Complementary DNA (cDNA) was prepared with RNA-dependent DNA polymerase from human globin messenger RNA (mRNA). Annealing and translation experimenta with total mRNA from circulating cells from a patient with heterozygous beta/heterozygous beta-delta-o thalassemia (beta-o/delta beta-o-thalassemia) demonstrated no detectable mRNA for beta-globin. cDNA enriched in sequences homologous to beta-globin mRNA was prepared by hydroxylapatite fractionation of hybrids formed between beta-o/delta beta-o-thalassemic mRNA and cDNA made from mRNA from a patient with alpha-thalassemia (hemoglobin H disease). The rate of annealing of this beta-enriched cDNA to normal human nuclear DNA was that of a sequence present as only a single copy per haploid genome. The beta-enriched cDNA annealed to the beta-o-delta beta-o-thalassemia total DNA with approximately the same kinetics as to normal DNA, indicating that no total gene deletion of beta-globin genes from the diploid genome has occurred, although the accuracy of the technique could not exclude with certainty a partial deletion or a deletion of a beta-globin gene from only one of the haploid genomes. This demonstrates that at least one of the beta-o- or the delta beta-o-thalassemia haploid genomes in this case contains a substantially intact beta-globin gene.

Adolescent↗
PubMed1977

Reconstitution of native human hemoglobin from separated globin chains and alloplex intermediates.

A complete experimental format is given for the reconstitution of human hemoglobin from the separated heme-free alpha- and beta-globin chains (alpha degrees, beta degrees) and hemin, by two alternative routes. Based on their oxygen binding properties, the reaction of the ferri-forms with reducing agent, and the response of the oxygen binding curves to pH variation and to the addition of the allosteric effector 2,3-diphosphoglycerate, the molecules are native. One reconstitution route uses direct addition of hemin to the separated globin chains with production of the separated subunits, which can then be recombined and reduced. This procedure occasions losses by precipitation in the heme-addition step except at high dilutions, and the yields are low. In the second pathway, either globin chain is mixed with the complementary untreated subunit to form the half-filled (with heme) intermediates, which combine stoichiometrically with hemin. No precipitation accompanies these reactions. For alpha-globin, the yield is about 50% because of incomplete combination with the heme-containing beta chain. For beta-globin, the yield is better than 70%. It is suggested that experiments intended to test either globin chain should use the second route in preparation for structural or functional comparisons with native hemoglobin.

Allosteric Site↗
PubMed1978

The isolation of duplex DNA fragments containing (dG.dC) clusters by chromatography on poly(rC)-Sephadex.

Duplex DNA containing oligo(dG.dC)-rich clusters can be isolated by specific binding to poly(rC)-Sephadex. This binding, probably mediated by the formation of an oligo(dG.dC)rC+ triple helix, is optimal at pH 5 in 50% formamide, 2 M LiCl; the bound DNA is recovered by elution at pH 7.5. Using this method we find that the viral DNAs PM2, lambda and SV40 contain at least 1, 1 and 2 sites for binding to poly(rC)-Sephadex, respectively. These binding sites have been mapped in the case of SV40; the binding sites can in turn be used for physical mapping studies of DNAs containing (dG.dC) clusters. Inspection of the sequence of the bound fragments of SV40 DNA shows that a (dG.dC)6-7 tract is required for the binding of duplex DNA to poly(rC)-Sephadex. Although about 60% of rabbit DNA cleaved with restriction endonuclease KpnI binds to poly(rC)-Sephadex, no binding is observed for the 5.1 kb DNA fragment generated by KpnI digestion, which contains the rabbit beta-globin gene. This indicates that oligo(dG.dC) clusters are not found close to the rabbit beta-globin gene.

Animals↗
PubMed2024

Use of 3D chaos game representation to quantify DNA sequence similarity with applications for hierarchical clustering.

A 3D chaos game is shown to be a useful way for encoding DNA sequences. Since matching subsequences in DNA converge in space in 3D chaos game encoding, a DNA sequence's 3D chaos game representation can be used to compare DNA sequences without prior alignment and without truncating or padding any of the sequences. Two proposed methods inspired by shape-similarity comparison techniques show that this form of encoding can perform as well as alignment-based techniques for building phylogenetic trees. The first method uses the volume overlap of intersecting spheres and the second uses shape signatures by summarizing the coordinates, oriented angles, and oriented distances of the 3D chaos game trajectory. The methods are tested using: (1) the first exon of the beta-globin gene for 11 species, (2) mitochondrial DNA from four groups of primates, and (3) a set of synthetic DNA sequences. Simulations show that the proposed methods produce distances that reflect the number of mutation events; additionally, on average, distances resulting from deletion mutations are comparable to those produced by substitution mutations.

Animals↗
PubMed1977

Prenatal diagnosis of beta-thalassaemia and sickle-cell anaemia. Experience with 24 cases.

Prenatal diagnosis of beta-thalassaemia and sickle-cell anaemia was attempted in 24 pregnancies. Adequate amounts of fetal blood (for studying globin-chain synthesis) were obtained in 22 cases. 4 cases of homozygous beta-thalassaemia and 2 of sickle-cell anaemia were diagnosed. The difference between the homozygous and non-homozygous states was well defined. Fetal bleeding from cord puncture and amnionitis resulted in the loss of three fetuses, and methods to avoid these complications are being devised. It is concluded that prenatal diagnosis of disorders of beta-globin synthesis is feasible.

Anemia, Sickle Cell↗
PubMed1979

Hemoglobin Cowtown (beta 146 HC3 His-Leu): a mutant with high oxygen affinity and erythrocytosis.

A new mutant, hemoglobin Cowtown, has been found in a white man and his father, both of whom have erythrocytosis. The father had previously been treated with 32P for polycythemia vera. The abnormal hemoglobin is not detectable on electrophoresis in alkaline buffers, but it resolves distinctively on electrophoresis in citrate agar, pH 6.0; similarly, the abnormal beta-globin chain does not separate from beta-A in urea 2-mercaptoethanol buffers of pH 8.9, but it moves anodically to beta-A at pH 6.0. Peptide chromatography and amino acid analysis of the beta chain reveal that the C-terminal histidine residue (beta 146) has been replaced by leucine. Like several other hemoglobins substituted at this residue, Hb Cowtown has a high oxygen affinity and a diminished Bohr effect.

Adult↗
PubMed1978

Sequence analysis of 5'[32P] labeled mRNA and tRNA using polyacrylamide gel electrophoresis.

Sequence analysis of 5'-[32P] labeled tRNA and eukaryotic mRNA using an adaptation of a method recently described by Donis-Keller, Maxam and Gilbert for mapping guanines, adenines and pyrimidines from the 5'-end of an RNA is described. In addition, a technique utilizing two-dimensional polyacrylamide gel electrophoresis for identification of pyrimidines within a sequence is described. 5'-[32P] Labeled rabbit beta-globin mRNA and N. crassa mitochondrial initiator tRNA were partially digested with T1- RNase for cleavage at G residues, with U2-RNase for cleavage at A residues, with an extracellular RNase from B. cereus for cleavage at pyrimidine residues and with T2-RNase or with alkali for cleavage at all four residues. The 5'-[32P] labeled partial digestion products were separated according to their size, by electrophoresis in adjacent lanes of a polyacrylamide slab gel and the location of G's, A's and of pyrimidines extending 60-80 nucleotides from the 5'-end of the RNA determined. Two-dimensional polyacrylamide gel electrophoresis was used to separate the 5'-[32P] labeled fragments present in partial alkali digests of a 5'-[32P] labeled mRNA. The mobility shifts corresponding to the difference of a C residue were distinct from those corresponding to a U residue and this formed the basis of a method for distinguishing between the pyrimidines.

Animals↗
PubMed1977

Isolation of chicken hemoglobin mRNA and synthesis of complementary DNA.

Chicken globin mRNA has been purified and partially characterized. Globin-specific sequences are found primarily as 9 S RNA, but also are found with ribosomal RNA, preferentially the 28 S moiety. The chicken globin mRNA preparation has been translated in the wheat germ and Krebs ascites cell-free systems. The products have been identified by sodium dodecyl sulfate-gel electrophoresis as the alpha- and beta-globin polypeptides. The globin mRNA is resolved into two asymmetric peaks by polyacrylamide gel electrophoresis in 98% formamide. The minor rapidly migrating peak consists primarily of alpha message while the major slowly migrating peak contains a mixture of alpha and beta messages. The synthesis of cDNA has been optimized and the products analyzed by polyacrylamide gel electrophoresis in 98% formamide. The products consist primarily of full copy transcripts that can be resolved into three discrete species.

Animals↗
PubMed2026

Compound Heterozygous Hemoglobin Minneapolis-Laos and Codon 41/42 (-TTCT) in a Thai Female Adult: A Case Report and Literature Review.

Thalassemia is a prevalent genetic disorder in Southeast Asia. The Hemoglobin Minneapolis-Laos variant is very rarely reported with only two previously published reports that profile a total of three patients. Here, we present the first reported case of compound heterozygous β zero (β0)-thalassemia and Hemoglobin Minneapolis-Laos in a 46-year-old Thai female. She presented at Siriraj Hospital (Bangkok, Thailand) with chronic microcytic anemia, which is a more severe phenotype than would be expected from either trait alone. Initial hemoglobin electrophoresis via high-performance liquid chromatography and capillary electrophoresis revealed elevated hemoglobin A2 (5.5% and 6.3%, respectively), which is a finding consistent with a β-thalassemia trait, but this finding failed to explain the full extent of her anemia. Next-generation sequencing was then performed to investigate for a congenital red blood cell disorder. The results identified the following two mutations in the β-globin gene (HBB): heterozygous β0-thalassemia codon 41/42 (-TTCT), and HBB c.356T >A, the latter of which is consistent with hemoglobin Minneapolis-Laos. This case highlights the importance of advanced genetic testing to diagnose rare hemoglobin variants that cannot be identified by conventional investigation and further contributes to our understanding of this rare combination's clinical phenotype.

Humans↗
PubMed2026

Low Prevalence of the HBB c.20A > T (HbS) Allele in a Turkish Cypriot Cohort: A Molecular Screening Study.

Sickle cell disease is caused by the HBB c.20A > T (p.Glu6Val; HbS) variant. Although Cyprus has a long-standing hemoglobinopathy prevention program, current population-specific data on HbS among Turkish Cypriots remain limited. Two hundred unrelated Turkish Cypriot adults were included. The HBB c.20A > T variant was genotyped by PCR-RFLP and confirmed by allele-specific real-time PCR. Genotype distribution was evaluated for Hardy-Weinberg equilibrium. No homozygous HbS genotype was detected. Three individuals were heterozygous carriers (AS), corresponding to a carrier frequency of 1.5%. The HbS allele frequency was 0.7%, and the genotype distribution was consistent with Hardy-Weinberg equilibrium (p = 0.916; chi-square = 0.011). HbS was uncommon in this Turkish Cypriot cohort. These findings support continued hemoglobinopathy surveillance and the integration of HbS counseling into existing premarital and population screening strategies, particularly as migration may alter local carrier frequencies over time.

Humans↗
PubMed2025

Engraftment and persistence of HBB base-edited hematopoietic stem cells in nonhuman primates.

Sickle cell disease (SCD) is caused by a single nucleotide change in the β-globin gene that adenine base editors can convert to the nonpathogenic Makassar β-globin variant. Here, we evaluated the long-term efficiency and off-target editing potential of autologous Makassar base editing in three rhesus macaques as a step toward human translation. Base editing of CD34+CD90+ hematopoietic stem cells (HSCs) at the Makassar locus reached greater than 60% efficiency using a bystander nucleotide as a proxy for the sickle cell target in cells from healthy macaques. No impact on myeloid and erythroid colony formation was seen, and clonal analysis revealed that >90% of HSCs were edited, >20% with biallelic editing. After transplantation of autologous gene-edited HSCs, all three macaques rapidly recovered neutrophils, red blood cells, and platelets with stable editing of 25.6%, on average, observed across nucleated blood cells. Similarly, the bone marrow stem cell compartment maintained over 20% of cells harboring mono- or biallelic edits. Off-target editing was assessed at over 900 candidate sites, with editing observed at eight sites, but no selection for or impact of these edits was observed throughout engraftment. These data support further translation of base editing of autologous HSCs for the treatment of patients with SCD.

Animals↗