title: Unequal homologous recombination between LINE-1 elements as a mutational mechanism in human genetic disease.
abstract: Unequal homologous recombination between repetitive genetic elements is one mechanism that mediates genome instability. We have characterized a homologous recombination event between two neighboring LINE-1 sequences in the human gene encoding the beta subunit of phosphorylase kinase (PHKB). It has lead to the deletion of 7574 nucleotides of genomic DNA including exon 8 of this gene, giving rise to glycogen storage disease through phosphorylase kinase deficiency. To our knowledge, this is the first example of a mutation due to unequal homologous recombination between LINE-1 elements. The sequence features of the recombining LINE-1 elements and of the recombination junction site, and possible reasons for the more frequent occurrence of unequal homologous recombination between Alu elements are discussed.
authors.affiliation: Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, Bochum, D-44780, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Burwinkel
authors.forename: M W
authors.initials: MW
authors.lastname: Kilimann
mesh_terms: D001483:Base Sequence; D004247:DNA; D006008:Glycogen Storage Disease / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010764:Phosphorylase Kinase / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004247:DNA; D010764:Phosphorylase Kinase