A delta-globin gene derived from patients with homozygous delta zero-thalassemia functions normally on transient expression in heterologous cells.
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.
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D005796:Genes; D005818:Genetic Engineering; D005914:Globins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D005810:Multigene Family; D013789:Thalassemia / Q000235:genetics* / Q000473:pathology
D005914:Globins