Nonsense and frameshift mutations in beta 0-thalassemia detected in cloned beta-globin genes.
The molecular basis for deficiency of beta-globin synthesis in beta-thalassemia was investigated by gene cloning and DNA sequencing. beta-Globin genes of two patients with beta 0-thalassemia were cloned in a phage lambda vector. Both beta-genes transcribed normally in vitro. The gene of an Italian individual had a single nucleotide substitution (C leads to T) in the codon for amino acid 39 that resulted in formation of a nonsense codon. In a Turkish individual, the cloned beta-globin gene had a dinucleotide deletion in the codon for amino acid 8. This frameshift mutation produced a termination codon at the position of the new 21st codon. Mutations that lead to premature termination of beta-globin synthesis appear to be among the common causes of beta 0-thalassemia in man.
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004274:DNA, Recombinant / Q000378:metabolism*; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000208:ethnology; D009154:Mutation; D013789:Thalassemia / Q000235:genetics*; D014158:Transcription, Genetic; D014421:Turkey / Q000208:ethnology
D003062:Codon; D004274:DNA, Recombinant; D005914:Globins