Investigating the mechanism of chromosomal deletion: Characterization of 39 deletion breakpoints in introns 47 and 48 of the human dystrophin gene

Luisa Toffolatti, Barbara Cardazzo, Carlo Nobile, Gian Antonio Danieli, Francesca Gualandi, Francesco Muntoni, Steve Abbs, Patrizia Zanetti, Corrado Angelini, Alessandra Ferlini, Marina Fanin, Tomaso Patarnello

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)523-530
Number of pages8
JournalGenomics
Volume80
Issue number5
DOIs
Publication statusPublished - 2002

Fingerprint

Dystrophin
Introns
Genetic Recombination
Double-Stranded DNA Breaks
Genes
Homologous Recombination
Nucleic Acid Databases

Keywords

  • Breakpoints
  • Deletion junctions
  • Dystrophin gene
  • Intron 47
  • Intron 48
  • Recombination mechanisms
  • Repetitive elements

ASJC Scopus subject areas

  • Genetics

Cite this

Investigating the mechanism of chromosomal deletion : Characterization of 39 deletion breakpoints in introns 47 and 48 of the human dystrophin gene. / Toffolatti, Luisa; Cardazzo, Barbara; Nobile, Carlo; Danieli, Gian Antonio; Gualandi, Francesca; Muntoni, Francesco; Abbs, Steve; Zanetti, Patrizia; Angelini, Corrado; Ferlini, Alessandra; Fanin, Marina; Patarnello, Tomaso.

In: Genomics, Vol. 80, No. 5, 2002, p. 523-530.

Research output: Contribution to journalArticle

Toffolatti, L, Cardazzo, B, Nobile, C, Danieli, GA, Gualandi, F, Muntoni, F, Abbs, S, Zanetti, P, Angelini, C, Ferlini, A, Fanin, M & Patarnello, T 2002, 'Investigating the mechanism of chromosomal deletion: Characterization of 39 deletion breakpoints in introns 47 and 48 of the human dystrophin gene', Genomics, vol. 80, no. 5, pp. 523-530. https://doi.org/10.1016/S0888-7543(02)96861-8
Toffolatti, Luisa ; Cardazzo, Barbara ; Nobile, Carlo ; Danieli, Gian Antonio ; Gualandi, Francesca ; Muntoni, Francesco ; Abbs, Steve ; Zanetti, Patrizia ; Angelini, Corrado ; Ferlini, Alessandra ; Fanin, Marina ; Patarnello, Tomaso. / Investigating the mechanism of chromosomal deletion : Characterization of 39 deletion breakpoints in introns 47 and 48 of the human dystrophin gene. In: Genomics. 2002 ; Vol. 80, No. 5. pp. 523-530.
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