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

✍ Scribed by Yôichi Iida


Publisher
Elsevier Science
Year
1990
Tongue
English
Weight
679 KB
Volume
145
Category
Article
ISSN
0022-5193

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✦ Synopsis


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.