scholarly journals Biochemical and Molecular analysis of the beta-globin gene on Saudi sickle cell anemia

2019 ◽  
Vol 26 (7) ◽  
pp. 1377-1384 ◽  
Author(s):  
Faris Q. Alenzi ◽  
Dalal S. AlShaya
Keyword(s):  
Molecular Analysis ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Globin Gene ◽  
Beta Globin ◽  
Beta Globin Gene

scholarly journals Fetal hemoglobin in sickle cell anemia: relation to regulatory sequences cis to the beta-globin gene. Multicenter Study of Hydroxyurea

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1604-1611 ◽  
Author(s):  
ZH Lu ◽  
MH Steinberg
Keyword(s):  
Gene Expression ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Regulatory Sequences ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Gamma Globin ◽  
Globin Gene Expression

Very different fetal hemoglobin levels among adult sickle cell anemia patients suggest genetic modulation of gamma-globin gene expression. In sickle cell anemia, different fetal hemoglobin levels are associated with distinct beta-globin gene haplotypes. Haplotype may be a marker for linked DNA that modulates gamma-globin gene expression. From 295 individuals with sickle cell anemia, we chose for detailed studies 53 patients who had the highest or the lowest fetal hemoglobin levels and 7 patients whose fetal hemoglobin levels were atypical of their haplotype. In these individuals, we examined portions of the beta- globin gene locus control region hypersensitive sites two and three, an (AT)x(T)y repeat 5′ to the beta-globin gene, a 4-bp deletion 5 to the A gamma T gene, promoters of both gamma-globin genes, 5′ flanking region of the G gamma-globin gene, and A gamma-globin gene IVS-II. Of the regions we studied all polymorphisms were always haplotype-linked and no additional mutations were present. This suggested that variations in these areas are uncommon mechanisms of fetal hemoglobin modulation in sickle cell anemia. Whereas unexamined cis-acting sequences may regulate gamma-globin gene transcription, trans-acting factors may play a more important role.

scholarly journals Production of F cells in sickle cell anemia: regulation by a genetic locus or loci separate from the beta-globin gene cluster

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1053-1058 ◽  
Author(s):  
SH Boyer ◽  
GJ Dover ◽  
GR Serjeant ◽  
KD Smith ◽  
SE Antonarakis ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Sickle Cell ◽  
Genetic Locus ◽  
Globin Gene ◽  
The United States ◽  
Beta Globin ◽  
Cell Production ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Sib Pairs

Abstract Levels of fetal hemoglobin (HbF) bearing reticulocytes (F reticulocytes) range from 2% to 50% in patients with sickle cell (SS) anemia. To learn whether any portion of such variation in F cell production is regulated by loci genetically separable from the beta- globin gene cluster, percentages of F reticulocytes were compared in 59 sib pairs composed solely of SS members, including 40 pairs from Jamaica and 19 from the United States. We reasoned that differences in F reticulocyte levels might arise (1) from any of several kinds of artifact, (2) via half-sib status, or (3) because one or more genes regulating F cell production segregate separately from beta S. We minimized the role of artifact by assay of fresh samples from 84 SS individuals, including both members of 38 sib pairs. In 78 of the 84 subjects, serial values for percent F reticulocytes fell within 99.9% confidence limits or were alike by t test (P greater than or equal to .05). This left 32 sib pairs for which F reticulocyte levels in each member were reproducible. When sib-sib comparisons were limited to these 32 pairs, percentages of F reticulocytes were grossly dissimilar within 12 Jamaican and 3 American sibships. Within them, the probability that sibs were alike was always less than or equal to .005 and usually less than or equal to 10(-4). We next minimized the contribution of half-sibs among Jamaicans by a combination of paternity testing and sib-sib comparison of beta-globin region DNA restriction fragment length polymorphisms, especially among discordant pairs. We thereafter concluded that at least seven to eight Jamaican pairs were composed of reproducibly discordant full sibs. There is thus little doubt that there are genes regulating between-patient differences in F cell production that are separate from the beta-globin gene cluster. Still unanswered is (1) whether or not these genes are actually linked to beta S, (2) why F reticulocyte levels in Americans tend to be lower than in Jamaicans, and (3) whether or not differences in F cell production among SS patients are regulated by several major loci or by only one.

Beta-Globin Gene Cluster Haplotypes in Yemeni Children with Sickle Cell Disease

2010 ◽  
Vol 123 (3) ◽  
pp. 182-185 ◽  
Author(s):  
Abdul-Wahab M. Al-Saqladi ◽  
Bernard J. Brabin ◽  
Hassan A. Bin-Gadeem ◽  
Warsha A. Kanhai ◽  
Marion Phylipsen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Gene Cluster ◽  
Sickle Cell ◽  
Globin Gene ◽  
Beta Globin ◽  
Cell Disease ◽  
Beta Globin Gene ◽  
Globin Gene Cluster

scholarly journals DNA sequence variation in a negative control region 5' to the beta- globin gene correlates with the phenotypic expression of the beta s mutation

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 787-792 ◽  
Author(s):  
J Elion ◽  
PE Berg ◽  
C Lapoumeroulie ◽  
G Trabuchet ◽  
M Mittelman ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Sickle Cell ◽  
Globin Gene ◽  
Phenotypic Expression ◽  
Fetal Hemoglobin ◽  
Negative Control ◽  
Globin Genes ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Hb S

The clinical diversity of sickle cell anemia is strongly related to the degree of intracellular hemoglobin S (Hb S) polymerization, which in turn is dependent on the intracellular concentration of Hb S. We have recently defined a region of DNA approximately 500 bp 5′ to the human beta-globin gene that acts as a silencer for the transcription of this gene and have shown that a polymorphism in this sequence is associated with a thalassemic phenotype of the beta-globin gene. In this work we have examined the correlation of DNA sequence polymorphisms in this silencer with binding of a previously identified putative repressor protein, BP1, and with the expression of Hb S in individuals heterozygous for the beta s allele. It was found that specific configurations of the motif, (AT)x(T)y, are homogeneous for the major haplotypes of the beta-globin gene cluster described on beta s chromosomes. Binding of BP1 was measured to DNA of three haplotypes: Indian, Benin, and Bantu. BP1 binds most tightly to DNA of the Indian haplotype, and these patients produce less beta s protein than Benin patients, whose DNA exhibits weaker affinity for BP1. Binding of BP1 is the weakest to DNA of the Bantu haplotype, which is associated with clinically more severe sickle cell symptoms. These data are consistent with the hypothesis that these polymorphisms may not be neutral and that the DNA sequence at this site may affect the expression of the beta s gene. Such an effect may be synergistic with other genetic variables, such as fetal hemoglobin levels, F-cell numbers, and the number of alpha-globin genes, in determining intracellular polymerization and, thus, the severity of the sickle cell syndromes.

scholarly journals Haplotypes of the beta-globin gene as prognostic factors in sickle-cell disease

1999 ◽  
Vol 5 (6) ◽  
pp. 1254-1258
Author(s):  
M. A. El Hazmi ◽  
A. S. Warsy ◽  
N. Bashir ◽  
A. Beshlawi ◽  
I. R. Hussain
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Presentation ◽  
Globin Gene ◽  
Beta Globin ◽  
Cell Disease ◽  
Beta Globin Gene ◽  
The North ◽  
Cell Gene

Wecollaborated with researchers from Egypt, Syrian Arab Republic and Jordan in a study of patients with sickle-cell disease from those countries, and from various parts of Saudi Arabia, in order to investigate the influence of genetics on the clinical presentation of the disease, and to attempt to determine the origin of the sickle-cell gene in Arabs. Our results suggest that beta-globin gene haplotypes influence the clinical presentation of sickle-cell disease, and that there are at least two major foci for the origin of the sickle-cell gene, one in the eastern part of Saudi Arabia, and the other in the populations of North Africa and the north-western part of the Arabian peninsula

Use of biotinylated probes for detecting sickle cell anemia.

1985 ◽  
Vol 31 (7) ◽  
pp. 1203-1206 ◽  
Author(s):  
G J Garbutt ◽  
J T Wilson ◽  
G S Schuster ◽  
J J Leary ◽  
D C Ward
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Genomic Dna ◽  
Globin Gene ◽  
Blot Hybridization ◽  
Beta Globin ◽  
Radioactive Materials ◽  
Dna Fragment ◽  
Cell Gene ◽  
Biotinylated Probes

Abstract Earlier, we reported that the 5' end of the normal beta-globin gene (beta) resides on a 1.14-kilobase DNA fragment, whereas the 5' end of the sickle cell gene (beta s) resides on a 1.34-kilobase fragment. In that blot hybridization analysis, we used genomic DNA digested with restricted endonuclease Mst II, and radioactive probes with short half-life. We demonstrate here that, if a biotinylated probe is used instead in a slightly modified procedure, sickle cell anemia can be quickly and directly detected if there is as much as 5 micrograms of total genomic DNA in the sample. This procedure obviates the special precautions necessary when radioactive materials are used.

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