title: Replication errors may contribute to the generation of large deletions and duplications in the dystrophin gene.
abstract: Frequent recurrent mutations of the human dystrophin gene lead to Duchenne and Becker muscular dystrophies. Although the approximately 2.5 Mb size of the gene may form a large target for mutations it is not clear to date which mechanisms promote the observed high frequency of spontaneous mutants (1 in 10,000 X-chromosomes) of which a high percentage (> 70%) are gross structural aberrations (deletions/duplications). In order to gain insight into possible molecular mechanisms we have cloned and sequenced the deletion junction fragments from two unrelated Duchenne patients. Our data, together with a short review on other cases from the literature, present evidence that errors of DNA replication may contribute to the generation of submicroscopic chromosome rearrangements.
authors.affiliation: Department of Human Genetics, University of Würzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Baldrich
authors.forename: M
authors.initials: M
authors.lastname: Baldrich
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: C R
authors.initials: CR
authors.lastname: Müller
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004261:DNA Replication; D016189:Dystrophin / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D009136:Muscular Dystrophies / Q000235:genetics; D015183:Restriction Mapping; D017384:Sequence Deletion
chemical_list: D016189:Dystrophin; D004247:DNA