A delta-globin gene derived from patients with homozygous delta zero-thalassemia functions normally on transient expression in heterologous cells.

Abstract

Three Japanese individuals with homozygous delta zero-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the beta-globin gene cluster. Nucleotide sequence analysis of the delta-globin gene cloned from each patient revealed a single nucleotide substitution (T-C) 77 base pairs 5' to the cap site, just upstream of the CCAAC box of the delta-globin gene. When introduced into COS cells, the gene was expressed at normal levels with proper processing of RNA. These results suggest that the complete suppression of delta-globin chain synthesis in these patients is not due to a defective promoter, a defective RNA processing or a chain terminator mutation, but rather to impaired regulation of gene expression specific to erythroid cells. The region around the CCAAC box may have a significant role in expression of the delta-globin gene in erythroid cells.

• Authors: T Nakamura, Y Takihara, Y Ohta, S Fujita, Y Takagi, Y Fukumaki
• Journal: Blood (Blood) Vol. 70 Issue 3 Pg. 809-13 (Sep 1987) ISSN: 0006-4971 [Print] United States
• PMID: 3476164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Globins

Topics

• Animals
• Cell Line
• Cloning, Molecular
• Gene Expression Regulation
• Genes
• Genetic Engineering
• Globins (genetics)
• Homozygote
• Humans
• Multigene Family
• Thalassemia (genetics, pathology)