Embryonic ζ-Globin Chains in Adults: a Marker for α-Thalassemia-1 Haplotype Due to a >17.5-kb Deletion

Abstract

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.

Sequence Divergence in the 3′ Untranslated Regions of Human ζ- and α-Globin mRNAs Mediates a Difference in Their Stabilities and Contributes to Efficient α-to-ζ Gene Developmental Switching

“…This model would predict that naturally occurring mutations which downregulate ␣-globin gene transcription would result in increased levels of -globin mRNA. In fact, this pattern is observed in individuals with some forms of deletional ␣-thalassemia who express especially low levels of ␣-globin mRNA (7,42). A detailed knowledge of these mechanisms would permit formulation of therapeutic strategies designed to alter the balance between ␣-and -globin gene expression through modulation of these posttranscriptional controls.…”

Routine Screening of (--^SEA) α-Thalassemia Deletion by an Enzyme-Linked Immunosorbent Assay for Embryonic ζ-Globin Chains

“…Thirdly, adult carriers of the SEA deletion express minute amounts of embryonic ζ-globin chain in erythrocytes [6]that can be demonstrated by immunologic techniques using anti-human ζ-globin chain antibodies [7, 8, 9, 10]. Immunocytological staining of red cells in peripheral blood smears with the anti-ζ antibody, which has been shown to be sensitive and specific for the detection of SEA carriers in adulthood [11, 12], requires fluorescent microscopy that necessitates regular and fairly sophisticated maintenance.…”

Development and validation of a ζ-globin-specific ELISA for carrier screening of the (−−SEA) α thalassaemia deletion

“…Previously conducted surveys examining the expression of the human embryonic ζ-globin gene have shown that minute amounts of the ζ-globin chain are present in the erythrocytes of adult SEA α thalassaemia carriers,13 14 and ζ-globin has been demonstrated as a marker for the SEA deletion α thalassaemia-1 haplotype 15. In addition, a simple monoclonal antibody (mAb) based assay for the ζ-globin chain has been developed to screen adult SEA carriers 16 17.…”