scholarly journals Human embryonic zeta-globin chains in fetal and newborn blood

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1409-1414 ◽  
Author(s):  
DH Chui ◽  
WC Mentzer ◽  
M Patterson ◽  
TA Iarocci ◽  
SH Embury ◽  
...  
Keyword(s):  
Cord Blood ◽  
Globin Gene ◽  
Globin Chains ◽  
Specific Radioimmunoassay ◽  
Alpha Globin ◽  
Term Newborns ◽  
Near Term ◽  
Almost All ◽  
Very High ◽  
Diabetic Mothers

Abstract A sensitive and specific radioimmunoassay (RIA) for human embryonic zeta-globin chains was used to study normal fetal blood and newborn cord blood as well as cord blood from newborns with alpha-thalassemias. From 17 weeks until 37 weeks of gestation, zeta-globin chains were present in almost all fetal and cord blood samples (0.27% +/- 0.15% in samples of weeks 17 through 30; 0.14% +/- 0.11% in samples of weeks 31 through 37). zeta-Globin chains were present in greater than 80% of cord blood hemolysates from normal, full-term newborns (0.15% +/- 0.11%) as well as from 16 near-term newborns of diabetic mothers (0.13% +/- 0.13%). zeta-Globin chains were not detected in normal infants aged 3 months to 2 years. In cord blood hemolysates from alpha-thalassemic newborns, the levels of zeta-globin chain content varied from very high to undetectable levels. Gene mapping of the zeta-alpha-globin gene cluster was performed in 12 newborns in whom cord blood zeta-globin chains had been determined. Newborns who were carriers of alpha- thalassemia-1 due to the (--SEA/) deletion had very high levels of zeta- globin chains (greater than 1.5%).

scholarly journals Human embryonic zeta-globin chains in fetal and newborn blood

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1409-1414 ◽  
Author(s):  
DH Chui ◽  
WC Mentzer ◽  
M Patterson ◽  
TA Iarocci ◽  
SH Embury ◽  
...  
Keyword(s):  
Cord Blood ◽  
Globin Gene ◽  
Globin Chains ◽  
Specific Radioimmunoassay ◽  
Alpha Globin ◽  
Term Newborns ◽  
Near Term ◽  
Almost All ◽  
Very High ◽  
Diabetic Mothers

A sensitive and specific radioimmunoassay (RIA) for human embryonic zeta-globin chains was used to study normal fetal blood and newborn cord blood as well as cord blood from newborns with alpha-thalassemias. From 17 weeks until 37 weeks of gestation, zeta-globin chains were present in almost all fetal and cord blood samples (0.27% +/- 0.15% in samples of weeks 17 through 30; 0.14% +/- 0.11% in samples of weeks 31 through 37). zeta-Globin chains were present in greater than 80% of cord blood hemolysates from normal, full-term newborns (0.15% +/- 0.11%) as well as from 16 near-term newborns of diabetic mothers (0.13% +/- 0.13%). zeta-Globin chains were not detected in normal infants aged 3 months to 2 years. In cord blood hemolysates from alpha-thalassemic newborns, the levels of zeta-globin chain content varied from very high to undetectable levels. Gene mapping of the zeta-alpha-globin gene cluster was performed in 12 newborns in whom cord blood zeta-globin chains had been determined. Newborns who were carriers of alpha- thalassemia-1 due to the (--SEA/) deletion had very high levels of zeta- globin chains (greater than 1.5%).

Alpha Globin Gene Mutation: A Major Determinant of Hydroxyurea Response in Transfusion-Dependent HbE-β-Thalassaemia

2019 ◽  
Vol 142 (3) ◽  
pp. 132-141
Author(s):  
Sujana Biswas ◽  
Rudra Ray ◽  
Kaushik Roy ◽  
Anish Bandyopadhyay ◽  
Kanjaksha Ghosh ◽  
...  
Keyword(s):  
Single Gene ◽  
Globin Gene ◽  
Poor Responders ◽  
Amplification Refractory Mutation System ◽  
Gene Deletions ◽  
Globin Chains ◽  
Hydroxyurea Treatment ◽  
Transfusion Requirements ◽  
F Cells ◽  
Alpha Globin

Thalassaemias are the most common inherited autosomal recessive single gene disorders characterised by chronic hereditary haemolytic anaemia due to absence or reduced synthesis of one or more of the globin chains. Haemoglobin E (HbE)-β-thalassaemia is the genotype responsible for approximately one-half of all cases of severe β-thalassaemia worldwide. This study proposes to evaluate response of hydroxyurea in reducing transfusion requirements of severe HbE-β-thalassaemia patients, and its correlation with foetal haemoglobin (HbF) level and α-mutation. Hydroxyurea was started at a baseline dose in 82 transfusion-dependent HbE-β-thalassaemia patients. HbF levels and %F-cells were measured. β-Thalassaemia mutations and α-globin gene deletions and triplications were detected by amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) and Gap-PCR, respectively. Patients were categorised as good (41.5%), moderate (31.7%), and poor responders (26.8%) based on their decrease in transfusion requirements. Nine patients were excellent responders who became transfusion independent. The mean increase in HbF levels and %F-cells after therapy was correlated with decrease in transfusion requirements. Patients having a deletion of the α-globin gene were better responders. The response was proportional to the number of α-globin gene deletions. We conclude that hydroxyurea treatment decreases transfusion requirements, and the response correlates with α-globin gene deletions.

scholarly journals Hb Bart's level in cord blood and deletions of alpha-globin genes

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 370-376 ◽  
Author(s):  
LE Lie-Injo ◽  
A Solai ◽  
AR Herrera ◽  
L Nicolaisen ◽  
YW Kan ◽  
...  
Keyword(s):  
Cord Blood ◽  
Blood Cells ◽  
Gene Deletion ◽  
Globin Gene ◽  
Globin Genes ◽  
Gene Deletions ◽  
Blood Samples ◽  
Alpha Globin ◽  
Abnormal Hemoglobin ◽  
Hb Bart's

Abstract The white blood cell DNA of 36 cord blood samples with Hb Bart's in the red blood cells was studied for alpha-globin gene deletions by hybridization of DNA fragments digested by the restriction endonucleases Eco RI, Hpa I, Bam HI, and Bgl II. All 16 DNA samples from cord blood with Hb Bart's below 3% and no other abnormal hemoglobin had one alpha-globin gene deletion (alpha thal2), except one which had two alpha-globin gene deletions (alpha thal1). Most of the alpha thal2 were of the rightward deletion alpha thal2 genotype. Two new types of alpha thal2 variation was found, probably due to a polymorphism somewhere in an area outside the alpha-globin gene. All 14 cases with Hb Bart's between 3.5% and 8.5% and no other abnormal hemoglobin had two alpha-globin gene deletions (alpha thal1), except one that did not have any alpha-globin gene deletion and one that had one alpha-globin gene deletion. Three DNA samples of cord blood with Hb Bart's accompanied by Hb CoSp did not have any alpha-globin gene deletion. Sixty-five DNA samples from cord blood without Hb Bart's or other abnormal hemoglobin had no alpha-globin gene deletions, except one that had one alpha-globin gene deletion (alpha thal2). Two of the 65 DNA samples were found to have triplicated alpha-globin gene loci.

scholarly journals Coinheritance of Alpha-3.7 Deletion and Hb Questembert [131alpha-2 Tct > CCT](Ser131>Pro)] in an African American Patient Results in an Alpha Thalassemia Phenotype

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4597-4597
Author(s):  
Asiya Shakir ◽  
Betty Pace ◽  
Niren Patel ◽  
Ferdane Kutlar ◽  
Abdullah Kutlar ◽  
...  
Keyword(s):  
African American ◽  
Conflicts Of Interest ◽  
Globin Gene ◽  
Membrane Damage ◽  
Medical Attention ◽  
African American Patient ◽  
Globin Chains ◽  
Mild Anemia ◽  
American Patient ◽  
Alpha Globin

Abstract Patients with Hemoglobin Questembert carry a Ser131Pro mutation in one of their alpha globin chains encoded by a TCT-CCT mutation of one of their alpha 2 globin gene. This mutation usually results in an unstable hemoglobin variant with mild anemia that is rarely symptomatic. Rarely these patients may show increased extravascular hemolysis during stress, due to oxidative membrane damage. Our patient is a 7 year old African American girl that came to medical attention due to severe anemia, reticulocytosis, absent haptoglobin levels, persistent jaundice and hyperbilirubinemia. Over a period of several years the patient progressed to develop marked splenomegaly with progressive anemia. Isoelectric focusing in this patient revealed Hb A, A2 and a variant "S" band which was less than 1% and thus not detectable by HPLC. We speculate that in the presence of limited alpha globin synthesis, due to a deletion of one α-2 gene and in the presence of a highly unstable alpha-2 variant, synthesis of wild-type alpha globin from the remaining alpa-1 gene is not sufficient to allow for normal alpha-globin/ beta-globin assembly. Furthermore the assembly of the alpha-globin Questembert into the hemoglobin tetramer is favored resulting in an extravascular hemolytic disorder. Disclosures No relevant conflicts of interest to declare.

scholarly journals Human embryonic zeta-globin gene expression in mouse-human hybrid erythroid cell lines

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1212-1217 ◽  
Author(s):  
HY Luo ◽  
AB Deisseroth ◽  
DH Chui
Keyword(s):  
Gene Expression ◽  
Globin Gene ◽  
Erythroid Cell ◽  
Hybrid Cells ◽  
Globin Chains ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Zeta Globin Gene ◽  
Murine Erythroleukemia ◽  
Globin Gene Expression

Abstract The human alpha-globin-like embryonic zeta-globin chains are present in abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, which is supplanted by the expression of alpha-globin chains. Adult individuals who are carriers of the (--SEA/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we constructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globin gene cluster (alpha alpha/) or the (--SEA/) type of alpha-thalassemia deletion. The results on the human zeta- globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene is cis to the (--SEA/) deletion, in parallel with the endogenous mouse alpha-globin gene expression. These data also show the importance of the DNA sequences within the (--SEA) deletion in regulating the expression of zeta-globin gene in cis during normal human hemoglobin ontogeny.

scholarly journals Umbilical cord blood acid-base analysis and the development of significant hyperbilirubinemia in near-term and term newborns: a cohort study

2017 ◽  
Vol 43 (1) ◽  
Author(s):  
Vincenzo Zanardo ◽  
Federico de Luca ◽  
Alphonse K. Simbi ◽  
Matteo Parotto ◽  
Pietro Guerrini ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Acid Base ◽  
Base Analysis ◽  
Term Newborns ◽  
Near Term

scholarly journals Detection of Hemoglobin (Hb) Variants By HPLC Screening in Cord Blood Units (CBU) Donated to the National Cord Blood Program (NCBP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2182-2182 ◽  
Author(s):  
Ludy Dobrila ◽  
Tracy Zhu ◽  
Dan Zamfir ◽  
Michal Tarnawski ◽  
Rodica Ciubotariu ◽  
...  
Keyword(s):  
Family History ◽  
Cord Blood ◽  
Sickle Cell ◽  
Globin Gene ◽  
Molecular Testing ◽  
Gene Deletions ◽  
Globin Chains ◽  
History Of ◽  
Clinically Significant ◽  
Hb C

Abstract Purpose. To evaluate the frequency and types of Hb abnormalities in CBU collected by the NCBP at the New York Blood Center. Background and Methods. Established in 1992, NCBP has collected and tested over 76,000 ethnically diverse CBU and manages an inventory of over 60,000 clinical grade CB products, including the first FDA-licensed (HEMACORD®). NCBP has released over 5,600 CBU for transplantation worldwide. To prevent transplants from donors affected with clinically significant hemoglobinopathy (HP), current Good Tissue Practices (cGTP) require Hb screening of all CBU before they are accepted to the public CB inventories. Clinically significant Hb disorders are caused by either structurally abnormal Hb variants (e.g., Hb S, Hb C, Hb E) or by decreased or absent production of α- or β-globin chains (thalassemia). Evaluation of NCBP CBU for possible HP includes: a) detailed family history for HP; b) complete blood count (CBC) and RBC indices, particularly mean corpuscular volume (MCV); c) screening using High-Performance Liquid Chromatography (HPLC) and d) confirmatory diagnostic testing using molecular methods (Hemoglobinopathy Reference Laboratory, Oakland, CA). To date, 76,312 CBU have been screened at the NCBP with the Bio-Rad Variant HPLC system using the Sickle Cell Short Program, a 3-min assay, specifically designed and FDA approved to provide a qualitative result for the presence of Hbs A, F, S, C, D and/or E in the neonate. Results.The HPLC chromatographic patterns were normal (Hb FA, where F is fetal and A is adult Hb) in 73,163 CBU (95.87%), and revealed an abnormal Hb in the remaining 3,149 CBU (4.13%), the majority of which were not clinically significant. The most frequent abnormal Hb phenotypes were, sickle cell trait (FAS): 1,755 CBU (57%), Hb E trait (FAE): 562 (18%) and Hb C trait (FAC): 506 (17%). Among the 3,149 CBU with abnormal Hb, 87 carried two genes for Hb disorders of clinical relevance, of which 54 were homozygous for sickle hemoglobin (Hb FS), 6 for Hb C (Hb FC) and 19 were double heterozygotes (Hb FSC). The HPLC results of all CBU with Hb traits and homozygous patterns were confirmed on repeat testing. In addition, all homozygous HPLC results were confirmed by molecular testing. Thalassemia and other abnormalities. Hb Barts (γ4) elutes "Fast" in the HPLC chromatogram. Its normally low concentration in CB increases when γ-chains replace non-functional or deleted α-globin chains in α-thalassemia (α-thal). Testing of all 76,312 NCBP CBU showed levels of Hb Barts from 0.5% to 34% of total Hb: 69.3% of the samples had Hb Barts level below 2.5%, 29.9% between 2.6 and 6.0% and 0.8% greater than 6.1%. Accordingly, for presumptive identification of α- or β-thalassemia, HPLC results must be interpreted together with red cell indices and family history. Of 788 CBU samples submitted for molecular (DNA) analyses as "possible thalassemia carriers", one was confirmed as Hb H disease (three α-globin genes deleted), 270 had α-thal trait (two α-globin gene deletions) and 517 had one or no α-globin gene deletion. The 270 CBU with α-thal trait had Hb Barts levels between 4.0% (above 6% in most cases) and 18.9% of total Hb. Further, 258 (95.6%) of the CBU with α-thal trait had MCV below 105 fL (range: 79.9 - 104.8 fL); only 12 cases (4.4%) had MCV >105 fL, all of which had levels of Hb Barts > 5%. The Hb H disease case had Fast Hb 34.2% (by HPLC) and MCV was 76.1 fL. β-thalassemia (β-thal): 4 CBU had β-thal major and in those, only Hb F (no Hb A) was seen in the HPLC result. Among 26 CBU found to have β-thal trait by the reference lab's DNA analysis, 16 (61.5%) were tested because of positive family history and 10 (38.5%) because of MCV <105 fL (seven CBU had both, low MCV and family history of thalassemia). Another CBU with a still-uncharacterized β-globin gene mutation had MCV <105 fL. HPLC patterns disclosing "Unknown Hbs" as "traits" in 5 CBU, were confirmed by molecular testing. Conclusions. HPLC is a simple to perform, accurate, comprehensive, inexpensive and fast screening method for HP in cord blood. All homozygous Hb detected by HPLC were confirmed by the reference lab. This is particularly relevant for sickle cell disease, as it is the most common HP in ethnic minority donors. Screening with HPLC, when used in combination with CBC and family history, is a useful tool to identify possible α- and β-thalassemia carriers in CBU. Molecular DNA testing is diagnostic in confirming and identifying globin gene deletions and mutations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Isolation of hybrid cell clones that contain deletion and non-deletion defects of alpha-thalassemia in man

Blood ◽  
1980 ◽  
Vol 55 (6) ◽  
pp. 992-996
Author(s):  
A Deisseroth ◽  
U Bode ◽  
R Lebo ◽  
A Dozy ◽  
YW Kan
Keyword(s):  
Human Chromosome ◽  
Hybrid Cell ◽  
Globin Gene ◽  
Close Correlation ◽  
Globin Genes ◽  
Chromosome 16 ◽  
Globin Chains ◽  
Cell Clones ◽  
Alpha Globin ◽  
Hybrid Clones

We have succeeded in isolating hybrid mouse erythroleukemia cell clones from a patient with hemoglobin H disease, which exhibit either deletion or nondeletion mutations of the human alpha-globin genes. Analysis of one of these hybrid clones that had retained a human chromosome 16 from the patient's cells showed that both human alpha-globin had been deleted. Several clones of another hybrid cell had retained a human chromsome 16 from the patient's cells, which contained both human alpha- globin genes on an EcoRI fragment of 23 kilobases (kb). These latter hybrid clones showed the presence of human alpha-globin chains at detectable but low levels. These studies show that there are two different types of human chromosome 16 in this patient and that the nondeletion mutation of human alpha-globin genes leading to hemoglobin H diseases in this patient acts in cis to the two alpha-globin genes remaining in his cells. The close correlation between the pattern of human alpha-globin gene expression in the patient and in the hybrid cells suggests that this method of transfer of human globin genes to rodent cells will be a useful one for study of mutations affecting the expression of differentiated genes that lead to disease in man.

scholarly journals Human embryonic zeta-globin gene expression in mouse-human hybrid erythroid cell lines

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1212-1217 ◽  
Author(s):  
HY Luo ◽  
AB Deisseroth ◽  
DH Chui
Keyword(s):  
Gene Expression ◽  
Globin Gene ◽  
Erythroid Cell ◽  
Hybrid Cells ◽  
Globin Chains ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Zeta Globin Gene ◽  
Murine Erythroleukemia ◽  
Globin Gene Expression

The human alpha-globin-like embryonic zeta-globin chains are present in abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, which is supplanted by the expression of alpha-globin chains. Adult individuals who are carriers of the (--SEA/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we constructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globin gene cluster (alpha alpha/) or the (--SEA/) type of alpha-thalassemia deletion. The results on the human zeta- globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene is cis to the (--SEA/) deletion, in parallel with the endogenous mouse alpha-globin gene expression. These data also show the importance of the DNA sequences within the (--SEA) deletion in regulating the expression of zeta-globin gene in cis during normal human hemoglobin ontogeny.

scholarly journals Hb Bart's level in cord blood and deletions of alpha-globin genes

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 370-376
Author(s):  
LE Lie-Injo ◽  
A Solai ◽  
AR Herrera ◽  
L Nicolaisen ◽  
YW Kan ◽  
...  
Keyword(s):  
Cord Blood ◽  
Blood Cells ◽  
Gene Deletion ◽  
Globin Gene ◽  
Globin Genes ◽  
Gene Deletions ◽  
Blood Samples ◽  
Alpha Globin ◽  
Abnormal Hemoglobin ◽  
Hb Bart's

The white blood cell DNA of 36 cord blood samples with Hb Bart's in the red blood cells was studied for alpha-globin gene deletions by hybridization of DNA fragments digested by the restriction endonucleases Eco RI, Hpa I, Bam HI, and Bgl II. All 16 DNA samples from cord blood with Hb Bart's below 3% and no other abnormal hemoglobin had one alpha-globin gene deletion (alpha thal2), except one which had two alpha-globin gene deletions (alpha thal1). Most of the alpha thal2 were of the rightward deletion alpha thal2 genotype. Two new types of alpha thal2 variation was found, probably due to a polymorphism somewhere in an area outside the alpha-globin gene. All 14 cases with Hb Bart's between 3.5% and 8.5% and no other abnormal hemoglobin had two alpha-globin gene deletions (alpha thal1), except one that did not have any alpha-globin gene deletion and one that had one alpha-globin gene deletion. Three DNA samples of cord blood with Hb Bart's accompanied by Hb CoSp did not have any alpha-globin gene deletion. Sixty-five DNA samples from cord blood without Hb Bart's or other abnormal hemoglobin had no alpha-globin gene deletions, except one that had one alpha-globin gene deletion (alpha thal2). Two of the 65 DNA samples were found to have triplicated alpha-globin gene loci.

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