Hemolysates from adults with the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion of both alpha-globin genes from the same chromosome were found to contain embryonic zeta (zeta)-globin chains (alpha-globin-like chains), as determined by a specific and sensitive radioimmunoassay and an electrophoretic technique. zeta-Globin chains were not present in hemolysates from adults with deletion of a single alpha-globin gene from one or both chromosomes. These results indicate that zeta-globin chains, which can be assayed by immunologic techniques, can serve as markers for the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion. The ability to detect zeta-globin chains may be useful in populations in which the gene frequency of the greater than 17.5-kb deletion is high, for screening couples at risk of having offspring with homozygous alpha-thalassemia.
DNA samples from numerous subjects of different racial and ethnic backgrounds, with or without various hemoglobinopathies (classical beta-thalassemia; silent beta-thalassemia, Hb E, sickle cell anemia), were studied for a rearrangement (+ATA; -T) at nucleotide -530 in the 5' flanking region of the beta-globin gene using amplified DNA and 32P-labeled synthetic oligonucleotide probes. The data show that this unusual sequence is a common feature among East-Asians and Blacks (particularly SS patients), and is not associated with mild thalassemic features typical for the silent form of beta-thalassemia, as has been suggested (5).
This study concerns the characterization of chromosomes with hybrid genes for Hb Lepore-Washington (44 chromosomes), for Hb Lepore-Baltimore (5 chromosomes), for Hb P-Nilotic (8 chromosomes), and for Hb Kenya (7 chromosomes) by determining a relatively large number of restriction enzyme polymorphism. Two, and possibly three, different Hb Lepore-Washington chromosomes were identified by specific haplotypes, while the haplotype of the Hb Lepore-Baltimore chromosome had its own characteristic pattern. A likely conclusion is that the crossovers leading to the formation of these chromosomes have occurred as independent events within the populations. Chromosomes with the delta beta-Lepore-Washington hybrid gene maintained specific characteristics (such as increased Hb F levels in heterozygotes, and high or low G gamma values in this Hb F) which have been observed in normal individuals with chromosomes having comparable haplotypes. Only one haplotype was observed for each of the chromosomes carrying either the beta delta-P-Nilotic hybrid gene or the A gamma beta hybrid gene of Hb Kenya.
Two families with Hb E diseases are described. In the Laotian family S, three homozygous Hb E were found. In the Vietnamese family H, double heterozygous Hb E-alpha-thalassemia-2 and Hb E-Hb H diseases were found. Anemia or hemolysis was absent in Hb E carriers, unless complicated by iron deficiency, the presence of severe alpha-thalassemia gene (Hb H disease), or oxidative drug (paraaminosalicylic acid). Moreover, iron deficiency or concurrent alpha-thalassemia genes resulted in a decreased amount of Hb E in its heterozygous carriers. Mild microcytosis and hypochromia were observed in Hb E heterozygotes, whereas the microcytosis and hypochromia were more pronounced in Hb E homozygotes. Globin chain synthesis studies yielded unbalanced alpha/non-alpha ratios in both heterozygotes and homozygotes (average ratios were 1.13 and 1.56, respectively). The unbalanced biosynthetic ratios with microcytosis and hypochromia in Hb E carriers represented a beta-thalassemia phenotype, which could be a result of reduced synthesis of beta E-globin mRNA, as suggested by recent hybridization studies.
Human embryonic {-globin chains are a-globin-like chains that are normally present during the first three months of gestation. In this investigation, C-globin chains measured by a specific and sensitive radioimmunoassay and by an electrophoretic technique were found to be present in all 7 patients studied with hereditary Hb H disease, and in 8 out of 24 patients with a-thalassemia trait. C-Globin chains were not detected in 20 other patients with (3-thalassemia trait. These results suggest that the deletion of two a-globin genes on the same chromosome is accompanied by the continued expression of embryonic {-globin genes in adult individuals.a-Thalassemia is a hereditary disorder in which a-globin chain synthesis is either decreased or absent. It is usually caused by complete deletion of one or more a-globin genes, although partial deletion as well as nondeletion abnormalities have been described (1). In homozygous a-thalassemia with complete deletion of all four a-globin genes, the 4-globin chains, normally present during the first 3 months of gestation, continue to be synthesized even in the third trimester (2-4). These t-globin chains combine with y-globin chains to form Hb Portland-i (Q2Y2), which accounts for about 10-15% of the hemoglobins present in infants with the Hb Bart's hydrops fetalis syndrome (5, 6). These infants are usually stillborn or die shortly after birth.Hereditary Hb H disease is caused by deletion of either three a-globin genes or, rarely, two a-globin genes in combination with an abnormal a-globin gene such as a Constant Spring (1). a-Thalassemia trait is commonly the result of either the deletion of two a-globin genes from one chromosome or the deletion of one a-globin gene from each of the two homologous chromosomes (1). In this study, evidence is presented that the embryonic ;-globin genes continue to be expressed in 7 patients with hereditary Hb H disease and in 8 out of 24 other patients with a-thalassemia trait. MATERIALS AND METHODSHematological Data. Hematological parameters were determined by standard laboratory procedures, using a Coulter S electronic counter. Hemoglobin studies, including starch gel electrophoresis, determinations of Hb A2 by microcolumn chromatography (normal range 1.8-3.3%) and Hb F by the Betke method (normal range 0.4-1.2%), were done as previously described (7). Hb H inclusion bodies in peripheral blood erythrocytes were carefully searched for under a light microscope, after the blood was incubated with brilliant cresyl blue (British Drug House) for 2 hr at 37°C (8).DEAE-cellulose column chromatography (9) was performed with a number of patients' hemolysate samples and the a/f,-globin synthetic ratio in peripheral blood reticulocytes was assessed in some patients (10). Hemolysates were electrophoresed in Triton X-100/urea/polyacrylamide gels (11), and the globin bands were stained with Coomassie blue and scanned by a Beckman densitometer (model CDS-200).Isolation of Hemoglobins and Globins. Hb Portland-i (t2Y2) was partially purified from the hem...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.