The 3 '-untranslated region of the dystrophin gene - conservation and consequences of loss

M J Greener, C A Sewry, F Muntoni, R G Roberts

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The 3'-untranslated region (3'UTR) of some vertebrate dystrophin genes shows an extraordinary degree and extent of conservation (better than that of many coding regions), a phenomenon that remains unexplained. We examine novel sequence and mutational data to explore the possible reasons for this. We show that loss of the human dystrophin 3'UTR is sufficient to cause Becker muscular dystrophy with pronounced reduction in dystrophin protein levels. The acquisition of dystrophin 3'UTR sequence from an amphibian and a cartilaginous fish allows us to refine previously identified functionally constrained regions which might account for the observed phenotype. These comprise (a) the open reading frame encoding the ancestral 'alternative' amphipathic C-terminal alpha-helix, normally removed from adult dystrophin by inclusion of a poorly conserved frameshifting penultimate exon, and (b) two highly conserved untranslated regions ('Lemaire A', 350 nucleotides and 'Lemaire D', 250 nucleotides) separated by a non-conserved 700-2000-nucleotide spacer. We consider the possibility that the 3'UTR may represent a significant target for pathogenic mutations.
Original languageEnglish
Pages (from-to)413 - 420
Number of pages8
JournalEuropean Journal of Human Genetics
Volume10
Issue number7
DOIs
Publication statusPublished - 2002

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