Unequal homologous recombination between LINE-1 elements as a mutational mechanism in human genetic disease

J Mol Biol. 1998 Apr 3;277(3):513-7. doi: 10.1006/jmbi.1998.1641.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA
  • Glycogen Storage Disease / enzymology*
  • Glycogen Storage Disease / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Phosphorylase Kinase / genetics*
  • Recombination, Genetic*
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Deletion*
  • Sequence Homology, Nucleic Acid


  • DNA
  • Phosphorylase Kinase

Associated data

  • GENBANK/Y15155