&Thalassemia Caused by Disruption of the Site for an Erythroid-Specific Transcription Factor, GATA-1, in the &Globin Gene Promoter

Delta-thalassemia is a complex group of inherited disorders of globin genes characterized by impaired synthesis of the &globin chain. The T-C substitution was detected at position -77 of the &globin gene isolated from three independent Japanese individuals who were homozygotes for ti-thalassemia. To elucidate the significance of the mutation in &globin gene expression, we investigated the genotype of three &thalassemia homozygotes and 58 normal individuals using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA. The mutation was observed in six alleles of three homozygotes, while no mutation was detected in 116 alleles of normal individuals, thereby indicating the close association of this mutation with the thalassemia phenotype. Since the mutation (FATCT-TGATCT) is located within the inverted binding motif of GATA-1 (T or A-G-A-TA-G or A), an erythroid cell-specific transcription factor, we did gel retardation assays using nuclear extracts from the