A DELTA-GLOBIN GENE DERIVED FROM PATIENTS WITH HOMOZYGOUS DELTA-DEGREES-THALASSEMIA FUNCTIONS NORMALLY ON TRANSIENT EXPRESSION IN HETEROLOGOUS CELLS

  • 1 September 1987
    • journal article
    • research article
    • Vol. 70  (3) , 809-813
Abstract
Three Japanese individuals with homozygous .delta.-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. Thees 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.