An intron nucleotide sequence variant in a cloned β-thalassaemia globin gene

Abstract

A 7.5 kb Hsu I restriction fragment of genomic DNA containing a β-globin gene has been isolated from a patient doubly heterozygous for β+ thalassaemia and a δβ (Lepore) globin fusion gene. This fragment must be derived from the chromosome carrying the β+-thalassaemia determinant. The gross structure of the cloned gene plus flanking sequences is indistinguishable from that of a normal β-globin gene. Within the 1606 base-pair transcribed region of the gene there is only one nucleotide difference from the normal β-globin gene sequence. This is a G→A replacement 21 nucleotides upstream from the 3′ terminus of the small intron. This nucleotide lies within a 10 base-pair sequence repeated in an inverted configuration near the 5′ terminus of the small intron. The nucleotide replacement may result in a precursor mRNA less amenable to RNA splicing than its normal counterpart. © 1981 IRL Press Limited.