title: Is the human dystrophin gene's intron structure related to its intron instability?
abstract: OBJECTIVE
  To study the human dystrophin gene molecular deletion mechanism, we analyzed breakpoint regions within junction fragments of deletion-type patients and investigated whether the dystrophin gene's intron structure might be related to intron instability.
  
  
  METHODS
  Junction fragments corresponding to exon 46 and 51 deletions were cloned. The breakpoint regions were sequenced, and the features of introns with available Genebank sequences were analyzed.
  
  
  RESULTS
  An analysis of junction fragment sequences corresponding to exon 46 and 51 deletions showed that all 5' and 3' breakpoints are located within repeat sequences. No small insertions, small deletions, or point mutations are located near the breakpoint junctions. By analyzing the secondary structure of the junction fragments, we demonstrated that all junction fragment breakpoints are located in non-matching regions of single-stranded hairpin loops. A high concentration of repetitive elements is found to be a key feature of many dystrophin introns. In total, 34.8% of the overall dystrophin intron sequences is composed of repeat sequences.
  
  
  CONCLUSIONS
  Repeat elements in many dystrophin gene introns are the key to their structural bases and reflect intron instability. As a result of the primary DNA sequences, single-stranded hairpin loops form, increasing the instability of the gene, and forming the base for breaks in the DNA. The formation of the single-stranded hairpins can result in reattachment of two different breakpoints, producing a deletion.
authors.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. wenlisheng@hotmail.com
authors.forename: Wenli
authors.initials: W
authors.lastname: Sheng
authors.forename: Jiangying
authors.initials: J
authors.lastname: Chen
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhu
authors.forename: Zhuolin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D016189:Dystrophin