scholarly journals The entire beta-globin gene cluster is deleted in a form of gamma delta beta-thalassemia

Blood ◽  
1983 ◽  
Vol 61 (6) ◽  
pp. 1269-1274
Author(s):  
ER Fearon ◽  
HH Jr Kazazian ◽  
PG Waber ◽  
JI Lee ◽  
SE Antonarakis ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Mexican American ◽  
Globin Gene ◽  
Dna Polymorphisms ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Endonuclease Mapping

We have used restriction endonuclease mapping to study a deletion involving the beta-globin gene cluster in a Mexican-American family with gamma delta beta-thalassemia. Analysis of DNA polymorphisms demonstrated deletion of the beta-globin gene from the affected chromosome. Using a DNA fragment that maps greater than 40 kilobases (kb) 5′ to the epsilon-gene as a probe, reduced amounts of normal fragments were found in the DNA of affected family members. Similar analysis using radiolabeled DNA fragments located 3′ to the beta-globin cluster has shown that the deletion extends more than 17 kb 3′ to the beta-gene, but terminates before the 3′ endpoint of the Ghanian HPFH deletion. Hence, this gamma delta beta-thalassemia deletion eliminates over 105 kb of DNA and is the first report of a deletion of the entire beta-globin gene cluster.

scholarly journals The entire beta-globin gene cluster is deleted in a form of gamma delta beta-thalassemia

Blood ◽  
1983 ◽  
Vol 61 (6) ◽  
pp. 1269-1274 ◽  
Author(s):  
ER Fearon ◽  
HH Jr Kazazian ◽  
PG Waber ◽  
JI Lee ◽  
SE Antonarakis ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Mexican American ◽  
Globin Gene ◽  
Dna Polymorphisms ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Endonuclease Mapping

Abstract We have used restriction endonuclease mapping to study a deletion involving the beta-globin gene cluster in a Mexican-American family with gamma delta beta-thalassemia. Analysis of DNA polymorphisms demonstrated deletion of the beta-globin gene from the affected chromosome. Using a DNA fragment that maps greater than 40 kilobases (kb) 5′ to the epsilon-gene as a probe, reduced amounts of normal fragments were found in the DNA of affected family members. Similar analysis using radiolabeled DNA fragments located 3′ to the beta-globin cluster has shown that the deletion extends more than 17 kb 3′ to the beta-gene, but terminates before the 3′ endpoint of the Ghanian HPFH deletion. Hence, this gamma delta beta-thalassemia deletion eliminates over 105 kb of DNA and is the first report of a deletion of the entire beta-globin gene cluster.

scholarly journals A novel basis for delta beta-thalassemia in a Chinese family

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1108-1113 ◽  
Author(s):  
GF Atweh ◽  
DE Zhu ◽  
BG Forget
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Beta Thalassemia ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Beta Globin ◽  
Hemoglobin F ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Alpha Beta

Abstract We have studied a Chinese family in which beta-thalassemia and delta beta-thalassemia were found in simple and compound heterozygous states. The delta beta-thalassemia heterozygote (the mother) had 22.3% hemoglobin F, of which 40% was G gamma and 60% A gamma; globin chain studies showed an alpha/beta + gamma ratio of 1.36. The compound heterozygote for delta beta-thalassemia and beta-thalassemia (the child) had the clinical picture of thalassemia intermedia and an alpha/beta + gamma ratio of 4.44. Gene mapping studies were performed using DNA from the affected child. Seventy kilobases of DNA in the beta- globin gene cluster starting upstream from the epsilon-globin gene and ending downstream from the beta-globin gene were mapped, and no detectable deletions or rearrangements were detected. In addition, heterozygosity was detected at multiple polymorphic restriction sites in and 3′ to the beta-globin gene, which excludes the possibility of a deletion of the entire beta-globin gene cluster. This is the first example of a nondeletion delta beta-thalassemia associated with increased expression of both G gamma and A gamma genes.

scholarly journals The 18- to 23-kb deletion of the Macedonian delta beta-thalassemia includes the entire delta and beta globin genes

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 971-974
Author(s):  
GD Efremov ◽  
N Nikolov ◽  
Y Hattori ◽  
I Bakioglu ◽  
TH Huisman
Keyword(s):  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Large Deletion ◽  
Beta Thalassemia ◽  
Globin Genes ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Restriction Sites ◽  
Endonuclease Mapping

Restriction endonuclease mapping analyses were made of DNA from a few members of a Macedonian family with hematological characteristics of delta beta-thalassemia, ie, microcytosis, normal HbA2 levels, and elevated levels of HbF (7% to 14%) with G gamma (average 40.5%) and A gamma T chains (average 59.5%). A large deletion of 18 to 23 kb was present with a 5′ breakpoint within a 670-bp segment of DNA between the HpaI and NcoI restriction sites 5′ to the delta globin gene, and a 3′ breakpoint between the BamHI and HpaI restriction sites located some 9 to 13 kb 3′ to the beta globin gene. This deletion is different from those present in other types of G gamma A gamma(delta beta)zero- thalassemia. The similarity of the hematological expression of these delta beta-thalassemic conditions which have somewhat comparable 5′ breakpoints supports the idea that an important fetal hemoglobin- controlling region lies between the psi beta and delta globin genes.

scholarly journals Interaction of two different disorders in the beta-globin gene cluster associated with an increased hemoglobin F production: a novel deletion type of (G) gamma + ((A) gamma delta beta)(0)-thalassemia and a delta(0)-hereditary persistence of fetal hemoglobin determinant

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 861-867
Author(s):  
M Losekoot ◽  
R Fodde ◽  
EJ Gerritsen ◽  
I van de Kuit ◽  
A Schreuder ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Beta Globin ◽  
Gamma Delta ◽  
Hemoglobin F ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Hereditary Persistence

We report two different disorders of the beta-globin gene cluster segregating in a Belgian family: a novel deletion that results in (G) gamma + ((A) gamma delta beta)(0)-thalassemia (thal) and a heterocellular hereditary persistence of foetal hemoglobin of the Swiss type linked to a delta(0)-thal gene (delta (0)-HPFH). Heterozygosity for the heterocellular HPFH brings about a moderate (3.4% to 8.24%) increase of hemoglobin (Hb) F having a G gamma/A gamma ratio of 4:1, whereas carriers of the G gamma + ((A) gamma delta beta)(0)-thal deletion show in their peripheral blood a considerably higher (15%) percentage of Hb F. Both defects interact in the compound heterozygotes for G gamma + ((A) gamma delta beta)(0)-thal and delta(0)-HPFH producing a further increase (up to 24%) of fetal Hb consisting entirely of G gamma chains. Molecular characterization of the (G) gamma + ((A) gamma delta beta)(0)-thal by means of Southern analysis showed that the deletion spans about 50 kb, removing the 3′ end of the A gamma- gene, the psi beta-, delta-, and beta-genes. A number of possible mechanisms leading to the overproduction of Hb F in HPFH and (G) gamma + ((A) gamma delta beta)(0)-thal will be discussed.

scholarly journals The 18- to 23-kb deletion of the Macedonian delta beta-thalassemia includes the entire delta and beta globin genes

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 971-974 ◽  
Author(s):  
GD Efremov ◽  
N Nikolov ◽  
Y Hattori ◽  
I Bakioglu ◽  
TH Huisman
Keyword(s):  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Large Deletion ◽  
Beta Thalassemia ◽  
Globin Genes ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Restriction Sites ◽  
Endonuclease Mapping

Abstract Restriction endonuclease mapping analyses were made of DNA from a few members of a Macedonian family with hematological characteristics of delta beta-thalassemia, ie, microcytosis, normal HbA2 levels, and elevated levels of HbF (7% to 14%) with G gamma (average 40.5%) and A gamma T chains (average 59.5%). A large deletion of 18 to 23 kb was present with a 5′ breakpoint within a 670-bp segment of DNA between the HpaI and NcoI restriction sites 5′ to the delta globin gene, and a 3′ breakpoint between the BamHI and HpaI restriction sites located some 9 to 13 kb 3′ to the beta globin gene. This deletion is different from those present in other types of G gamma A gamma(delta beta)zero- thalassemia. The similarity of the hematological expression of these delta beta-thalassemic conditions which have somewhat comparable 5′ breakpoints supports the idea that an important fetal hemoglobin- controlling region lies between the psi beta and delta globin genes.

scholarly journals Interaction of two different disorders in the beta-globin gene cluster associated with an increased hemoglobin F production: a novel deletion type of (G) gamma + ((A) gamma delta beta)(0)-thalassemia and a delta(0)-hereditary persistence of fetal hemoglobin determinant

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 861-867 ◽  
Author(s):  
M Losekoot ◽  
R Fodde ◽  
EJ Gerritsen ◽  
I van de Kuit ◽  
A Schreuder ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Beta Globin ◽  
Gamma Delta ◽  
Hemoglobin F ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Hereditary Persistence

Abstract We report two different disorders of the beta-globin gene cluster segregating in a Belgian family: a novel deletion that results in (G) gamma + ((A) gamma delta beta)(0)-thalassemia (thal) and a heterocellular hereditary persistence of foetal hemoglobin of the Swiss type linked to a delta(0)-thal gene (delta (0)-HPFH). Heterozygosity for the heterocellular HPFH brings about a moderate (3.4% to 8.24%) increase of hemoglobin (Hb) F having a G gamma/A gamma ratio of 4:1, whereas carriers of the G gamma + ((A) gamma delta beta)(0)-thal deletion show in their peripheral blood a considerably higher (15%) percentage of Hb F. Both defects interact in the compound heterozygotes for G gamma + ((A) gamma delta beta)(0)-thal and delta(0)-HPFH producing a further increase (up to 24%) of fetal Hb consisting entirely of G gamma chains. Molecular characterization of the (G) gamma + ((A) gamma delta beta)(0)-thal by means of Southern analysis showed that the deletion spans about 50 kb, removing the 3′ end of the A gamma- gene, the psi beta-, delta-, and beta-genes. A number of possible mechanisms leading to the overproduction of Hb F in HPFH and (G) gamma + ((A) gamma delta beta)(0)-thal will be discussed.

scholarly journals A novel basis for delta beta-thalassemia in a Chinese family

Blood ◽  
1986 ◽  
Vol 68 (5) ◽  
pp. 1108-1113
Author(s):  
GF Atweh ◽  
DE Zhu ◽  
BG Forget
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Beta Thalassemia ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Beta Globin ◽  
Hemoglobin F ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Alpha Beta

We have studied a Chinese family in which beta-thalassemia and delta beta-thalassemia were found in simple and compound heterozygous states. The delta beta-thalassemia heterozygote (the mother) had 22.3% hemoglobin F, of which 40% was G gamma and 60% A gamma; globin chain studies showed an alpha/beta + gamma ratio of 1.36. The compound heterozygote for delta beta-thalassemia and beta-thalassemia (the child) had the clinical picture of thalassemia intermedia and an alpha/beta + gamma ratio of 4.44. Gene mapping studies were performed using DNA from the affected child. Seventy kilobases of DNA in the beta- globin gene cluster starting upstream from the epsilon-globin gene and ending downstream from the beta-globin gene were mapped, and no detectable deletions or rearrangements were detected. In addition, heterozygosity was detected at multiple polymorphic restriction sites in and 3′ to the beta-globin gene, which excludes the possibility of a deletion of the entire beta-globin gene cluster. This is the first example of a nondeletion delta beta-thalassemia associated with increased expression of both G gamma and A gamma genes.

Beta-Globin Gene Cluster Haplotypes of Amerindian Populations from the Brazilian Amazon Region

1994 ◽  
Vol 44 (3) ◽  
pp. 142-149 ◽  
Author(s):  
João Farias Guerreiro ◽  
Mauro Silvério Figueiredo ◽  
Marco Antonio Zago
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Brazilian Amazon ◽  
Amazon Region ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Brazilian Amazon Region

scholarly journals Z-DNA-forming sites within the human beta-globin gene cluster.

1996 ◽  
Vol 93 (2) ◽  
pp. 780-784 ◽  
Author(s):  
V. Muller ◽  
M. Takeya ◽  
S. Brendel ◽  
B. Wittig ◽  
A. Rich
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Z Dna

scholarly journals The inactive beta globin gene on a gamma delta beta thalassemia chromosome has a normal structure and functions normally in vitro

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 766-770
Author(s):  
PT Curtin ◽  
YW Kan
Keyword(s):  
Globin Gene ◽  
Large Deletion ◽  
Beta Thalassemia ◽  
Ribonuclease Protection Assay ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Thalassemia Minor

We have previously described an English family with gamma delta beta- thalassemia in which a large deletion stops 25 kilobases (kb) upstream from the beta-globin gene locus, and yet the beta-globin gene is inactive in vivo. Affected family members had a beta-thalassemia minor phenotype with a normal hemoglobin A2 level. Gene mapping showed that these subjects were heterozygous for a chromosome bearing a large deletion that began in the G gamma-globin gene, extended through the epsilon-globin gene, and continued upstream for at least 75 kb. The A gamma-, delta-, and beta-globin gene loci on this chromosome were intact. To examine the possibility that an additional defect was present in the beta-globin gene, we cloned, sequenced, and examined the expression of the beta-globin gene from the affected chromosome. No mutation was found in the beta-globin gene sequence from 990 base-pairs 5′ to the cap site to 350 basepairs 3′ to the polyadenylation signal. The gene was subcloned into an expression vector and introduced into HeLa cells. Analysis of RNA derived from these cells, using a ribonuclease protection assay, revealed qualitatively and quantitatively normal transcription. Thus a structurally and functionally normal beta-globin gene is inactive in the presence of a large deletion more than 25 kb upstream. The loss of beta-globin gene function may be due to disturbance of chromatin conformation caused by the deletion or may be the result of loss of upstream sequences that are necessary for beta-globin gene expression in vivo.

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