Base substitution in an intervening sequence of a beta+-thalassemic human globin gene.

作者：Richard A. Spritz, Pudur Jagadeeswaran, Prabhakara V. Choudary, Paul Andrew Biro, James T. Elder, Jon K. deRiel, James L. Manley, M L Gefter, Bernard G. Forget, S M Weissman · 发表于：Proceedings of the National Academy of Sciences · 年份：1981 · DOI：10.1073/pnas.78.4.2455 · 被引用次数：232 · 研究领域：Hemoglobinopathies and Related Disorders、RNA modifications and cancer、Folate and B Vitamins Research

beta globin gene fragments from a patient with homozygous beta+-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro trancription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the beta+-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of beta globin mRNA precursor molecules in beta+-thalassemia.