Analysis of 22 deletion breakpoints in dystrophin intron 49

• DOI: 10.1007/s00439-002-0721-7
• Publication Date: 2003-02-13T00:27:25Z
• Authors: Carlo Nobile; Luisa Toffolatti; Francesca Rizzi; Barbara Simionati; Vincenzo Nigro; Barbara Cardazzo; Tomaso Patarnello; Giorgio Valle; Gian Danieli
• Keywords: 0303 health sciences; Base Sequence; Molecular Sequence Data; Chromosome Breakage; deletion breakpoint; Polymerase Chain Reaction; Introns; Dystrophin; Muscular Dystrophy, Duchenne; 03 medical and health sciences; DMD; Humans; Chromosome Deletion; gene

Over 60% of Duchenne and Becker muscular dystrophies are caused by deletions spanning tens or hundreds of kilobases in the dystrophin gene. The molecular mechanisms underlying the loss of DNA at this genomic locus are not yet understood. By studying the distribution of deletion breakpoints at the genomic level, we have previously shown that intron 49 exhibits a higher relative density of breakpoints than most dystrophin introns. To determine whether the mechanisms leading to deletions in this intron preferentially involve specific sequence elements, we sublocalized 22 deletion endpoints along its length by a polymerase-chain-reaction-based approach and, in particular, analyzed the nucleotide sequences of five deletion junctions. Deletion breakpoints were homogeneously distributed throughout the intron length, and no extensive homology was observed between the sequences adjacent to each breakpoint. However, a short sequence able to curve the DNA molecule was found at or near three breakpoint junctions.