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

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Abstract
Transcriptional analysis of 5 different cloned [human] .beta.-thalassemia 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 promotor mutation. Three genes contain different single base changes in the 1st intervening sequence (IVS) 5'' splice site. One mutation, at IVS1 position 1, inactivates the splice site completely; the other 2, at IVS1 positions 5 and 6, reduce its activity. Each mutation activates the same 3 cryptic splice sites. The 5th gene contains a single base change within IVS2 at position 745, which results in the formation of abnormal .beta.-globulin RNA that contains an extra exon.