title: Investigating the mechanism of chromosomal deletion: characterization of 39 deletion breakpoints in introns 47 and 48 of the human dystrophin gene.
abstract: The region of the dystrophin gene containing introns 45-50 is characterized by a high rate of recombination events that give rise to large deletions causing dystrophinopathy. The nucleotide sequence of this intronic region has recently been released in GenBank. With the aim of further understanding the mechanism favoring the occurrence of these deletions, we have characterized the distribution of introns 47 and 48 deletion endpoints in 39 dystrophinopathy patients. In 14 of these patients we were able to sequence the break junction. On these sequences we were able to identify several intronic motifs that could predispose to DNA double-strand breaks. Our results, combined with other literature data, show that unequal homologous recombination is a very poorly represented event in the dystrophin gene, whereas junction features are suggestive of a model of recombination in which DNA double-strand breaks are incorrectly repaired by a nonhomologous end-joining mechanism. The correlation among recombination rate, deletion frequency, and percentage of repetitive elements is discussed.
authors.affiliation: Dipartimento di Biologia, Università di Padova, Padova, 35121, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Toffolatti
authors.forename: Barbara
authors.initials: B
authors.lastname: Cardazzo
authors.forename: Carlo
authors.initials: C
authors.lastname: Nobile
authors.forename: Gian Antonio
authors.initials: GA
authors.lastname: Danieli
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Steve
authors.initials: S
authors.lastname: Abbs
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zanetti
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
authors.forename: Marina
authors.initials: M
authors.lastname: Fanin
authors.forename: Tomaso
authors.initials: T
authors.lastname: Patarnello
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D019457:Chromosome Breakage; D016189:Dystrophin / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D016189:Dystrophin