scholarly journals Analysis of delta-globin gene mutations in Greek cypriots

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1647-1651
Author(s):  
P Trifillis ◽  
A Kyrri ◽  
E Kalogirou ◽  
A Kokkofitou ◽  
P Ioannou ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Pcr Amplification ◽  
Rapid Identification ◽  
Restriction Enzyme Digestion ◽  
Globin Genes ◽  
Pcr Products ◽  
Direct Mutation ◽  
In Cis ◽  
Greek Cypriots

We recently described four delta-globin gene mutations in Greek Cypriots studied by polymerase chain reaction (PCR) amplification and automated fluorescence-based DNA sequence analysis (Blood 78:3298, 1991). Selective restriction enzyme digestion of PCR products facilitated direct mutation detection. Twenty-eight additional samples from unrelated Cypriots with Hb A2 levels ranging from 0.6% to 3.6% were studied by PCR and showed the following: twelve had the delta 27 (ala-->ser) mutation, one was heterozygous for the delta IVS-2 AG-->GG change, and none had either the delta 116 (arg-->cys) or delta 141 (leu- ->pro) mutations. The remaining samples were divided into two groups: 11 with borderline normal Hb A2 values that were not pursued; and four with abnormal Hb A2 values. The delta-globin genes from these four samples were sequenced and the same four changes identified in each: a C-->T at -199, a C-->T at codon 4 (thr-->ile), a silent C-->T at codon 97, and an AT deletion at position 722 in IVS-2. The codon 4 change abolishes a Ple I site whereas the codon 97 creates an Nla III site, thus facilitating rapid identification. All four changes are in cis position, suggesting that the -199 C-->T, the C-->T at codon 97, and the AT deletion in IVS-2 are neutral polymorphisms present on the codon 4 (thr-->ile) chromosome. DNA haplotype analysis suggests all five delta-globin gene mutant alleles arose independently on different chromosomal backgrounds.

scholarly journals Analysis of delta-globin gene mutations in Greek cypriots

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1647-1651 ◽  
Author(s):  
P Trifillis ◽  
A Kyrri ◽  
E Kalogirou ◽  
A Kokkofitou ◽  
P Ioannou ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Pcr Amplification ◽  
Rapid Identification ◽  
Restriction Enzyme Digestion ◽  
Globin Genes ◽  
Pcr Products ◽  
Direct Mutation ◽  
In Cis ◽  
Greek Cypriots

Abstract We recently described four delta-globin gene mutations in Greek Cypriots studied by polymerase chain reaction (PCR) amplification and automated fluorescence-based DNA sequence analysis (Blood 78:3298, 1991). Selective restriction enzyme digestion of PCR products facilitated direct mutation detection. Twenty-eight additional samples from unrelated Cypriots with Hb A2 levels ranging from 0.6% to 3.6% were studied by PCR and showed the following: twelve had the delta 27 (ala-->ser) mutation, one was heterozygous for the delta IVS-2 AG-->GG change, and none had either the delta 116 (arg-->cys) or delta 141 (leu- ->pro) mutations. The remaining samples were divided into two groups: 11 with borderline normal Hb A2 values that were not pursued; and four with abnormal Hb A2 values. The delta-globin genes from these four samples were sequenced and the same four changes identified in each: a C-->T at -199, a C-->T at codon 4 (thr-->ile), a silent C-->T at codon 97, and an AT deletion at position 722 in IVS-2. The codon 4 change abolishes a Ple I site whereas the codon 97 creates an Nla III site, thus facilitating rapid identification. All four changes are in cis position, suggesting that the -199 C-->T, the C-->T at codon 97, and the AT deletion in IVS-2 are neutral polymorphisms present on the codon 4 (thr-->ile) chromosome. DNA haplotype analysis suggests all five delta-globin gene mutant alleles arose independently on different chromosomal backgrounds.

scholarly journals Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

A silencer element from the alpha-globin gene inhibits expression of beta-like genes

1988 ◽  
Vol 8 (11) ◽  
pp. 5047-5051
Author(s):  
G F Atweh ◽  
J M Liu ◽  
H E Brickner ◽  
X X Zhu
Keyword(s):  
Globin Gene ◽  
Expression System ◽  
Globin Genes ◽  
Beta Globin ◽  
Base Pair Fragment ◽  
Alpha Globin ◽  
In Trans ◽  
Cis And Trans ◽  
In Cis ◽  
Silencer Element

We have studied the cis and trans interactions of the alpha- and beta-globin genes in a transient expression system. We found that the alpha-globin gene inhibited beta-globin expression in cis but not in trans. The silencer element responsible for this inhibition was localized to a 259-base-pair fragment at the 5' end of the alpha-globin gene.

scholarly journals Glyceraldehyde-3-Phosphate Dehydrogenase-Encoding Gene as a Useful Taxonomic Tool for Staphylococcusspp.

2000 ◽  
Vol 38 (12) ◽  
pp. 4351-4355 ◽  
Author(s):  
Javier Yugueros ◽  
Alejandro Temprano ◽  
Beatriz Berzal ◽  
Marı́a Sánchez ◽  
Carmen Hernanz ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Fragment Length Polymorphism ◽  
Pcr Amplification ◽  
Rapid Identification ◽  
Pcr Products ◽  
Dna Fragment ◽  
Encoding Gene ◽  
Staphylococcus Hominis ◽  
Staphylococcus Simulans ◽  
Very High

The gap gene of Staphylococcus aureus, encoding glyceraldehyde-3-phosphate dehydrogenase, was used as a target to amplify a 933-bp DNA fragment by PCR with a pair of primers 26 and 25 nucleotides in length. PCR products, detected by agarose gel electrophoresis, were also amplified from 12 Staphylococcusspp. analyzed previously. Hybridization with an internal 279-bp DNA fragment probe was positive in all PCR-positive samples. No PCR products were amplified when other gram-positive and gram-negative bacterial genera were analyzed using the same pair of primers.AluI digestion of PCR-generated products gave 12 different restriction fragment length polymorphism (RFLP) patterns, one for each species analyzed. However, we could detect two intraspecies RFLP patterns in Staphylococcus epidermidis,Staphylococcus hominis, and Staphylococcus simulans which were different from the other species. An identical RFLP pattern was observed for 112 S. aureusisolates from humans, cows, and sheep. The sensitivity of the PCR assays was very high, with a detection limit for S. aureuscells of 20 CFU when cells were suspended in saline. PCR amplification of the gap gene has the potential for rapid identification of at least 12 species belonging to the genusStaphylococcus, as it is highly specific.

scholarly journals Identification of four novel delta-globin gene mutations in Greek Cypriots using polymerase chain reaction and automated fluorescence- based DNA sequence analysis

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3298-3305 ◽  
Author(s):  
P Trifillis ◽  
P Ioannou ◽  
E Schwartz ◽  
S Surrey
Keyword(s):  
Polymerase Chain Reaction ◽  
Dna Sequence ◽  
Restriction Enzyme ◽  
Globin Gene ◽  
Pcr Amplification ◽  
Enzyme Digestion ◽  
Acceptor Site ◽  
Restriction Enzyme Digestion ◽  
Chain Reaction ◽  
Polymerase Chain

Abstract The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia was amplified by polymerase chain reaction (PCR), and DNA sequence determined using an automated fluorescence-based sequencer. Four novel mutations were identified: a G----T change at codon 27 that results in an alanine to serine change; a C----T change at codon 116 converting arginine to cysteine; a T----C change at codon 141 converting leucine to proline; and an AG----GG change at the consensus 3′-acceptor site in IVS-2. While the latter is clearly a thalassemic mutation, the low hemoglobin A2 in the first three may be due to either decreased production or instability of the altered delta-globin chain. All four mutations may be detected by PCR amplification of genomic DNA followed by restriction enzyme digestion. Two mutations abolish restriction sites while two create new cleavage sites. Screening for molecular defects that cause delta-thalassemia or unstable delta-globin by PCR amplification and restriction enzyme digestion will lead to correct diagnosis of beta/delta-thalassemia compound heterozygotes and improved genetic counseling.

scholarly journals A silencer element from the alpha-globin gene inhibits expression of beta-like genes.

1988 ◽  
Vol 8 (11) ◽  
pp. 5047-5051 ◽  
Author(s):  
G F Atweh ◽  
J M Liu ◽  
H E Brickner ◽  
X X Zhu
Keyword(s):  
Globin Gene ◽  
Expression System ◽  
Globin Genes ◽  
Beta Globin ◽  
Base Pair Fragment ◽  
Alpha Globin ◽  
In Trans ◽  
Cis And Trans ◽  
In Cis ◽  
Silencer Element

We have studied the cis and trans interactions of the alpha- and beta-globin genes in a transient expression system. We found that the alpha-globin gene inhibited beta-globin expression in cis but not in trans. The silencer element responsible for this inhibition was localized to a 259-base-pair fragment at the 5' end of the alpha-globin gene.

scholarly journals Genotype-phenotype correlation of HbH disease in northern Iraq

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.

scholarly journals Human alpha-globin genes demonstrate autonomous developmental regulation in transgenic mice.

1991 ◽  
Vol 11 (7) ◽  
pp. 3786-3794 ◽  
Author(s):  
M Albitar ◽  
M Katsumata ◽  
S A Liebhaber
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Globin Gene ◽  
Globin Genes ◽  
Beta Globin ◽  
Developmental Control ◽  
Beta Globin Gene ◽  
Human Adult ◽  
Alpha Globin ◽  
In Cis

Recent studies have demonstrated that transcriptional activation of the human adult beta-globin transgene in mice by coinsertion of the beta-globin cluster locus control region (beta-LCR) results in loss of its adult restricted pattern of expression. Normal developmental control is reestablished by coinsertion of the fetal gamma-globin transgene in cis to the adult beta-globin gene. To test the generality of this interdependence of two globin genes for their proper developmental control, we generated transgenic mice in which the human adult alpha-globin genes are transcriptionally activated by the beta-LCR either alone or in cis to their corresponding embryonic zeta-globin gene. In both cases, the human globin transgenes were expressed at the appropriate developmental period. In contrast to the beta-globin gene, developmental control of the human adult alpha-globin transgenes appears to be autonomous and maintained even when activated by an adjacent locus control region.

scholarly journals Genotype-Phenotype Correlation of HbH Disease in Northern Iraq

2020 ◽  
Author(s):  
Rawand P Shamoon ◽  
Ahmed K Yassin ◽  
Ranan K Polus ◽  
Mohamed D DaherAli
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.Method: 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 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.

scholarly journals Genotype-Phenotype Correlation of HbH Disease in Northern Iraq

2020 ◽  
Author(s):  
Rawand P Shamoon ◽  
Ahmed K Yassin ◽  
Ranan K Polus ◽  
Mohamed D DaherAli
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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