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Specific transcription and RNA splicing defects in five cloned β-thalassaemia genes

Naturevolume 302pages591596 (1983) | Download Citation

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Abstract

Transcriptional analysis of five different cloned β-thalassaemia genes introduced into cultured mammalian cells revealed specific defects in transcription and RNA splicing. A single base change 87 base pairs to the 5′ side of the mRNA cap site significantly lowers the level of transcription and therefore appears to represent a promoter mutation. Three genes contain different single base changes in the first intervening sequence (IVS) 5′ splice site. One mutation, at IVS1 position 1, inactivates the splice site completely; the other two, at IVS I positions 5 and 6, reduce its activity. Each mutation activates the same three cryptic splice sites. The fifth gene contains a single base change within IVS2 at position 745, which results in the formation of abnormal β-globin RNA that contains an extra exon.

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Affiliations

  1. Department of Biochemistry and Molecular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    • Richard Treisman
    •  & Tom Maniatis
  2. Children's Hospital Medical Center, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    • Stuart H. Orkin

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https://doi.org/10.1038/302591a0

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