CHARACTERIZATION OF HUMAN Gγ AND Aγ FETAL GLOBIN GENES

AbstractMouse models of sickle cell disease (SCD) that faithfully switch from fetal to adult hemoglobin (Hb) have been important research tools that accelerated advancement towards treatments and cures for SCD. Red blood cells (RBCs) in these animals sickled in vivo, occluded small vessels in many organs and resulted in severe anemia like in human patients. SCD mouse models have been valuable in advancing clinical translation of some therapeutics and providing a better understanding of the pathophysiology of SCD. However, mouse models vary greatly from humans in their anatomy and physiology and therefore have limited application for certain translational efforts to transition from the bench to bedside. These differences create the need for a higher order animal model to continue the advancement of efforts in not only understanding relevant underlying pathophysiology, but also the translational aspects necessary for the development of better therapeutics to treat or cure SCD. Here we describe the development of a humanized porcine sickle cell model that like the SCD mice, expresses human ɑ-, β− and γ-globin genes under the control of the respective endogenous porcine locus control regions (LCR). We also describe our initial characterization of the SCD pigs and plans to make this model available to the broader research community.

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Black α-Thalassemia-1: Partial Characterization of an ∼80 KB Deletion Which Includes the ξ- and α-Globin Genes

Hemoglobin ◽

10.3109/03630269308997487 ◽

1993 ◽

Vol 17 (4) ◽

pp. 345-353 ◽

Cited By ~ 2

Author(s):

T. H. J. Huisman ◽

L-H. Gu ◽

J-C. Liu ◽

Y-J. Fei ◽

E. L.D. Walker

Keyword(s):

Partial Characterization ◽

Globin Genes

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Isolation and characterization of the complete chicken β-globin gene region: frequent deletion of the adult β-globin genes in λ

Nucleic Acids Research ◽

10.1093/nar/9.15.3731 ◽

1981 ◽

Vol 9 (15) ◽

pp. 3731-3746 ◽

Cited By ~ 26

Author(s):

Bryant Villeponteau ◽

Harold Martinson

Keyword(s):

Globin Gene ◽

Gene Region ◽

Globin Genes ◽

Isolation And Characterization

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Identification and Characterization of Two Novel and Differentially Expressed Isoforms of Humanα2- andα1-Globin Genes

Hemoglobin ◽

10.3109/03630269.2012.699488 ◽

2012 ◽

Vol 36 (5) ◽

pp. 421-432 ◽

Cited By ~ 2

Author(s):

Reza Ghassemifar ◽

Luke Forster ◽

Talal Qadah ◽

Jill Finlayson

Keyword(s):

Differentially Expressed ◽

Globin Genes ◽

Identification And Characterization

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Use of oligonucleotide hybridization in the characterization of a beta zero-thalassemia gene (beta 37 TGG----TGA) in a Saudi Arabian family [published erratum appears in Blood 1986 Jul;68(1):323]

Blood ◽

10.1182/blood.v67.4.1185.bloodjournal6741185 ◽

1986 ◽

Vol 67 (4) ◽

pp. 1185-1188

Author(s):

CD Boehm ◽

CE Dowling ◽

PG Waber ◽

PJ Giardina ◽

HH Jr Kazazian

Keyword(s):

Genomic Dna ◽

Globin Gene ◽

Point Mutations ◽

Saudi Arabian ◽

Globin Genes ◽

Beta Globin ◽

Nucleotide Substitutions ◽

Exon 2 ◽

Oligonucleotide Hybridization

Analysis of restriction site polymorphisms in the beta-globin gene cluster of a Saudi Arabian female with beta zero-thalassemia demonstrated that both of her beta-globin genes were missing a nonpolymorphic AvaII site in exon 2. Examination of the normal nucleotide sequence surrounding this AvaII site revealed that either of two nucleotide substitutions, TGG----TAG or TGG----TGA, could produce a nonsense codon at codon 37 and eliminate the AvaII site. Consequently, two oligonucleotides (19-mers spanning codons 36 through 41 and containing either TAG or TGA at codon 37) were synthesized and hybridized against genomic DNA of the proband and her family. Specific hybridization with one of the oligomers demonstrated that the patient's beta o-thalassemia was the result of homozygosity for the TGG----TGA mutation at codon 37. In certain cases, oligonucleotide hybridization using genomic DNA may obviate the need for gene cloning and sequencing in the characterization of point mutations.

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Characterization of the DNA Pattern in the Vicinity of a Replication Origin Located Upstream from the Domain of Chicken α-Globin Genes

Nuclear Structure and Function ◽

10.1007/978-1-4613-0667-2_78 ◽

1990 ◽

pp. 377-382

Author(s):

Sergey V. Razin ◽

Avtandil G. Kalandadze ◽

Eka G. Kintsurashvili ◽

Yegor S. Vassetzky

Keyword(s):

Replication Origin ◽

Globin Genes ◽

Dna Pattern

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Genotype-phenotype correlation of HbH disease in northern Iraq

BMC Medical Genetics ◽

10.1186/s12881-020-01141-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Rawand P. Shamoon ◽

Ahmed K. Yassin ◽

Ranan K. Polus ◽

Mohamad D. Ali

Keyword(s):

Globin Gene ◽

Gene Mutations ◽

Globin Genes ◽

Phenotype Correlation ◽

Deletion Mutations ◽

Northern Iraq ◽

Screening And Prevention ◽

First Time ◽

Hbh Disease

Abstract Background HbH disease results from dysfunction of three, less commonly two, α-globin genes through various combinations of deletion and non-deletion mutations. Characterization of the mutations and the underlying genotypes is fundamental for proper screening and prevention of thalassaemia in any region. The aim of this study was to explore the genetic arrangements of HbH disease and to correlate the genotypes with the clinical phenotypes. Methods A total of 44 HbH disease patients were enrolled in this study. They were clinically and haematologically assessed. The patients were tested for 21 common α-globin gene mutations using multiplex PCR and reverse hybridization. According to the genotype, the patients were categorized into two separate sub-groups, deletion and non-deletion types HbH disease. Results Within the studied HbH disease patients, eight different α-globin gene mutations were detected in nine different genetic arrangements. The --MED and -α3.7 deletions were the two most frequently encountered mutations (37.5 and 35.2% respectively). Patients with deletion genotypes constituted 70.4%. The most common detected genotype was --MED/−α3.7 (59.1%), followed by αpoly-A1α/αpoly-A1α (13.6%). For the first time, coinheritance of two relatively mild mutations (−α3.7/ααAdana) was unpredictably detected in a 1.5 year-old child with Hb of 7.1 g/dL. Conclusion The HbH disease patients’ clinical characteristics were variable with no ample difference between the deletion and non-deletion types. These results can be of benefit for the screening and management of thalassaemia in this region.

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