High-resolution chromosomal localization of the β-gene of the human β-globin gene complex by in situ hybridization

1985 ◽  
Vol 39 (4) ◽  
pp. 269-274 ◽  
Author(s):  
C.C. Lin ◽  
P.N. Draper ◽  
M. De Braekeleer
Keyword(s):  
In Situ Hybridization ◽  
High Resolution ◽  
Chromosomal Localization ◽  
Globin Gene ◽  
Gene Complex ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Gene

scholarly journals RFLP Haplotypes of beta-Globin Gene Complex of beta-Thalassemic Chromosomes in Koreans

2002 ◽  
Vol 17 (4) ◽  
pp. 475 ◽  
Author(s):  
Young Joon Lee ◽  
Sung Sup Park ◽  
Ji Yeon Kim ◽  
Han Ik Cho
Keyword(s):  
Globin Gene ◽  
Gene Complex ◽  
Beta Globin ◽  
Beta Globin Gene

scholarly journals Precise localization of human beta-globin gene complex on chromosome 11.

1979 ◽  
Vol 76 (10) ◽  
pp. 5239-5242 ◽  
Author(s):  
J. Gusella ◽  
A. Varsanyi-Breiner ◽  
F. T. Kao ◽  
C. Jones ◽  
T. T. Puck ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Complex ◽  
Beta Globin ◽  
Precise Localization ◽  
Chromosome 11 ◽  
Beta Globin Gene

scholarly journals Large Deletions Involving the Beta Globin Gene Complex: Genotype-Phenotype Correlation of 119 Cases

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3374-3374
Author(s):  
Molly Susan Hein ◽  
Jennifer L Oliveira ◽  
Kenneth C Swanson ◽  
Patrick A Lundquist ◽  
Joella A Yungerberg ◽  
...  
Keyword(s):  
Control Region ◽  
Globin Gene ◽  
Locus Control Region ◽  
Microcytic Anemia ◽  
Beta Thalassemia ◽  
Gene Complex ◽  
Beta Globin ◽  
Gamma Delta ◽  
Beta Globin Gene ◽  
Large Deletions

Abstract Background: Large deletions involving the beta globin complex are relatively rare. They can be categorized generally into five groups by deletion size and/or location: 1) beta zero thalassemia (BZT); 2) delta beta thalassemia (DBT); 3) hereditary persistence of fetal hemoglobin (HPFH); 4) gamma delta beta thalassemia (GDBT); and 5) epsilon gamma delta beta thalassemia (EGDBT). These deletions are not well understood but often have significant clinical impact, either when present alone or in combination with other hemoglobin mutations. In this study, we analyze phenotypic and molecular data on a large number of cases with deletions in the beta globin gene complex to better classify these five groups of deletions as they occur in isolation. Methods: A query of the routine clinical testing patient files from the Mayo Clinic Metabolic Hematology and Molecular Genetics Laboratories from 2010 to 2015 identified 179 patients with a deletion confirmed by a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. Twenty-four probes sets were placed from the 5' locus control region (LCR) to the 3' hypersensitivity region, spanning the beta globin gene complex. Using a Luminex LX200 flow cytometer, a gene dosage ratio was calculated for each probe set using the median fluorescent intensity value collected. The size and location of the deletion and patient phenotype were compared. Results: Of the 179 total cases, the following large deletions were identified: beta gene (HBB) (n = 47), delta (HBD) through HBB (n = 105), A-gamma (HBG2) through HBB (n = 20), and locus control region (LCR) through HBB (n = 7). One case had a deletion involving the LCR epsilon with the rest of the complex left intact. A subset (n = 60) of cases had compound hemoglobin mutations that altered the phenotype. The BZT cases had relatively high Hb A2 levels and variable Hb F levels consistent with promotor region loss. The main differences between DBT and HPFH included Hb F and Hb A2 levels. GDBT cases presented with median Hb F levels higher than that observed in DBTs, normal Hb A2, and microcytic anemia. EGDBT cases had variable features according to age of the patient and Hb F level; severe microcytic anemia was observed in neonates, milder microcytic anemia in young children, and microcytosis without anemia in an adult case. The phenotypic features of 119 patients with isolated large deletions are compiled in table 1. Conclusion: In general, all five categories of large deletions in an isolated heterozygous state can present with microcytic anemia and are typically benign with the exception of transient severe microcytic anemia in neonatal EGDBT cases. Although phenotypes associated with large deletions involving the beta globin gene complex are frequently distinctive, significant phenotypic overlap can be seen in a subset of cases. These cases require molecular analysis due to their clinical importance when in combination with another beta globin gene complex mutation for an adequate diagnosis and treatment approach. Table 1. Deletion type Age n HbF (%) HbA2 (%) Hb (g/dL) MCV (fL) RBC (10^12/L) RDW (%) MCH (pg/cell) BZT 20 6.3 (0.6-94.4) 6.8 (3.4-11.6) 11.1 (8.3-14.5) 65.4 (60.8-77.2) 5.4 (4.2-6.2) 19.2 (16.6-21.2) 20.9 (18.3-25.7) DBT 56 10.6 (2.7-22.4) 2.7 (2.5-3.1) 11.7 (8.6-14.4) 68.9 (61.3-83.5) 5.3 (4.1-7.3) 21.4 (18.2-26.8) 21.6 (19.9-39.2) HPFH 23 25.9 (17.6-39.7) 2.0 (1.5-2.4) 11.6 (8.1-16.7) 78.4 (60.2-101.9) 4.4 (3.0-6.3) 17.5 (14.1-22.3) 25.4 (17.6-29.7) GDBT 14 13.3 (8.2-19.0) 2.6 (1.8-2.7) 11.0 (8.6-14.1) 72.5 (57.9-82.1) 5.1 (3.5-6.2) 20.6 (17.4-23.5) 22 (17.9-25.1) EGDBT* 28 Y 1 0.3 3 13.3 59.4 6.9 15.4 19.2 1-4 Y 3 0.9 (0-1.6) 3.2 (2.9-3.5) 9.5 (8.8-13.3) 57.8 (57.6-59.4) 5.2 (4.9-6.9) 16.6 (15.4-17.4) 18.5 (18.1-19.2) <6 month 2 21.4 (14.8-27.9) 2.6 (2.2-2.9) 6.3 (6.0-6.6) 61.3 (59.9-62.6) 3.4 (3.3-3.3) 21.5 (21.2-21.7) 18.4 (18.1-18.7) medians, (min, max); *stratified by age Disclosures No relevant conflicts of interest to declare.

scholarly journals Two independent genetic factors in the beta-globin gene cluster are associated with high G gamma-levels in the HbF of SS patients

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 452-457 ◽  
Author(s):  
JG Gilman ◽  
TH Huisman
Keyword(s):  
Gene Cluster ◽  
Restriction Site ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Globin Gene Cluster ◽  
Polymorphic Restriction Site ◽  
Polymorphic Restriction ◽  
Beta Gene

The gamma-chains of fetal hemoglobin (HbF) of newborn babies are composed of about 70% G gamma and 30% A gamma. In most babies, the G gamma value declines postnatally to 40%, but in about 20% of black SS patients from Georgia, 5 years and older, the G gamma level remains high at 60%. Moreover, some 3% to 4% of black newborns have high G gamma values of 85%. PstI digestion of DNA of one such high G gamma baby and of one normal newborn showed the former to be heterozygous for the -G gamma-G gamma- and -G gamma-A gamma-chromosomes. Only about one fourth of high G gamma SS patients were such heterozygotes, while three fourths were -G gamma-A gamma-/-G gamma-A gamma-homozygotes. Analysis of DNA of 38 SS patients without the -G gamma-G gamma-chromosome showed a correlation of G gamma values with genotype at one polymorphic restriction site: at the HincII site in the psi beta gene, all -G gamma- A gamma-/-G gamma-A gamma-homozygotes with high G gamma were +/- or +/+, while low G gamma individuals were all -/-. Family studies, involving analyses at four polymorphic sites (HindIII sites in the G gamma and A gamma genes and HincII sites in the psi beta gene and 3′ to it), suggested the association of an unidentified high G gamma genetic determinant with haplotype + - + +. This indicates that a genetic factor causing high G gamma levels in SS patients is closely linked to the -G gamma-A gamma-psi beta region of the beta-globin gene cluster.

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