β-Thalassemia in China: a Systematic Molecular Characterization of β-Thalassemia Mutations

Abstract

In order to initiate a program of prenatal diagnosis for the prevention of β-thalassemia in China, we have begun systematic studies of the β-thal assemia mutations among the Chinese. DNA polymorphisms in the β-globin gene cluster were examined in 46 β-thalassemia chromosomes. Six different haplotypes were observed. One β-thalassemia gene associated with a new haplotype was cloned and sequenced. The mutation was a single base substitution (A→G) at position -29 within the highly conserved proximal promoter element (the “TATA” box). This mutation was not observed previously in the Chinese. The β-thalassemia genes were further screened with oligonucleotide probes specific for all known mutations in the Chinese. Five mutations were identified and accounted for 35 β-thalassemia alleles.