title: The 5' region of intron 11 of the dystrophin gene contains target sequences for mobile elements and three overlapping ORFs.
abstract: We have characterised the 2371 bp 5' end of intron 11 of the dystrophin gene. Comparative analysis of this intronic region revealed homologies with the following sequences: regions containing mobile elements; target sites for numerous transcription factors, two resolvases, and a histone-like DNA binding protein; three eukaryotic promoters. In addition, we identified three partially overlapping ORFs, and transcription analysis confirmed that one of these is expressed, representing the first gene reported to overlap the human dystrophin gene. We have also characterised a 136 bp sequence rearranged in intron 11 in a patient affected by X-linked dilated cardiomyopathy due to a dystrophinopathy. This is a multiple copy sequence with features of a repetitive element. Its comparative analysis showed a very high homology with human genomic and EST regions, adjacent and clustered with Alu, LINE1, and THE elements. The pattern of homology suggests that it may represent a novel Alu-like, transcriptionally active sequence with a possible retrotransposable capacity. We hypothesise that the 5' region of the dystrophin intron 11, containing common target areas for the insertion of mobile elements, may have a role in the rearrangement of this novel Alu-like sequence.
authors.affiliation: Department of Paediatrics & Neonatal Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom. aferlini@rpms.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Ferlini
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics; D003001:Cloning, Molecular; D004251:DNA Transposable Elements / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D005807:Genes, Overlapping / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D016189:Dystrophin