Quantification analysis of 5'-splice signal sequences in mRNA precursors. Mutations in 5'-splice signal sequence of human beta-globin gene and beta-thalassemia

J Theor Biol. 1990 Aug 23;145(4):523-33. doi: 10.1016/s0022-5193(05)80486-2.

Abstract

Concerning the signals which direct excision of introns from mRNA precursors in higher eukaryotic genes, consensus 9-nucleotide sequence, (CA)AG/GT(AG)AGT, has been proposed with the 5'-splice site, but actual 5'-splice site sequences differ from it in a greater or lesser degree. We analyzed 5'-splice site sequence of human beta-globin gene by quantification method (categorical discriminant analysis) proposed previously. Analysis of 13-nucleotide sequences and deleted sequences showed that 9-nucleotide sequences in the consensus region are almost sufficient to define 5'-splice signal. To confirm this view, we examined a number of beta-globin mutant genes, where nucleotide changes occur at the authentic 5'-splice site of the first intron and cause beta-thalassemia phenotype. Our method could explain why such mutations abolish the 5'-splice site and cryptic 5'-splice sites are activated.

MeSH terms

  • Base Sequence
  • Globins / genetics
  • Humans
  • Models, Genetic*
  • Molecular Sequence Data
  • Mutation
  • RNA Precursors / genetics*
  • RNA Splicing / genetics*
  • Thalassemia / genetics

Substances

  • RNA Precursors
  • Globins