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"Silent" nucleotide substitution in codon 24 of a beta+ thalassemia globin gene activates splice site in coding sequence RNA.
Prog Clin Biol Res. 1983; 134:123-6.PC

Abstract

A beta+-thalassemia globin gene was isolated from the genome of a black patient by molecular cloning. DNA sequence analysis revealed only a single difference between this gene and the normal human beta-globin gene--adenine is substituted for thymine in the third position of codon 24. This mutation is silent at the protein sequence level. We compared the function of this beta+-thalassemia gene with the normal human beta-globin gene in monkey kidney cells using plasmid expression vectors. The codon 24 substitution activates a 5' splice site that involves the guanine-thymine dinucleotide present in codon 25, 16 nucleotides upstream from the normal exon 1-intron I boundary. Splices at the abnormal 5' site in the coding sequence are completed with the normal 3' splice site at the end of intron I. This splicing abnormality leads to a fourfold decrease in the accumulation of normally processed beta-globin mRNA, thereby causing the beta+-thalassemia phenotype.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

6664994

Citation

Humphries, R K., et al. ""Silent" Nucleotide Substitution in Codon 24 of a Beta+ Thalassemia Globin Gene Activates Splice Site in Coding Sequence RNA." Progress in Clinical and Biological Research, vol. 134, 1983, pp. 123-6.
Humphries RK, Ley T, Goldsmith ME, et al. "Silent" nucleotide substitution in codon 24 of a beta+ thalassemia globin gene activates splice site in coding sequence RNA. Prog Clin Biol Res. 1983;134:123-6.
Humphries, R. K., Ley, T., Goldsmith, M. E., Kantor, J. A., Cline, A. C., & Nienhuis, A. W. (1983). "Silent" nucleotide substitution in codon 24 of a beta+ thalassemia globin gene activates splice site in coding sequence RNA. Progress in Clinical and Biological Research, 134, 123-6.
Humphries RK, et al. "Silent" Nucleotide Substitution in Codon 24 of a Beta+ Thalassemia Globin Gene Activates Splice Site in Coding Sequence RNA. Prog Clin Biol Res. 1983;134:123-6. PubMed PMID: 6664994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - "Silent" nucleotide substitution in codon 24 of a beta+ thalassemia globin gene activates splice site in coding sequence RNA. AU - Humphries,R K, AU - Ley,T, AU - Goldsmith,M E, AU - Kantor,J A, AU - Cline,A C, AU - Nienhuis,A W, PY - 1983/1/1/pubmed PY - 1983/1/1/medline PY - 1983/1/1/entrez SP - 123 EP - 6 JF - Progress in clinical and biological research JO - Prog Clin Biol Res VL - 134 N2 - A beta+-thalassemia globin gene was isolated from the genome of a black patient by molecular cloning. DNA sequence analysis revealed only a single difference between this gene and the normal human beta-globin gene--adenine is substituted for thymine in the third position of codon 24. This mutation is silent at the protein sequence level. We compared the function of this beta+-thalassemia gene with the normal human beta-globin gene in monkey kidney cells using plasmid expression vectors. The codon 24 substitution activates a 5' splice site that involves the guanine-thymine dinucleotide present in codon 25, 16 nucleotides upstream from the normal exon 1-intron I boundary. Splices at the abnormal 5' site in the coding sequence are completed with the normal 3' splice site at the end of intron I. This splicing abnormality leads to a fourfold decrease in the accumulation of normally processed beta-globin mRNA, thereby causing the beta+-thalassemia phenotype. SN - 0361-7742 UR - https://www.unboundmedicine.com/medline/citation/6664994/"Silent"_nucleotide_substitution_in_codon_24_of_a_beta+_thalassemia_globin_gene_activates_splice_site_in_coding_sequence_RNA_ L2 - http://www.diseaseinfosearch.org/result/814 DB - PRIME DP - Unbound Medicine ER -