UNEQUAL HOMOLOGOUS RECOMBINATION BETWEEN LINE-1 ELEMENTS AS A MUTATIONAL MECHANISM IN HUMAN GENETIC-DISEASE

Unequal homologous recombination between repetitive genetic elements i s one mechanism that mediates genome instability. We have characterize d a homologous recombination event between two neighboring LINE-1 sequ ences in the human gene encoding the beta subunit of phosphorylase kin ase (PHKB). It has lead to the deletion of 7574 nucleotides of genomic DNA including exon 8 of tl-Lis gene, giving rise to glycogen storage disease through phosphorylase kinase deficiency. To our knowledge, thi s is the first example of a mutation due to unequal homologous recombi nation between LINE-1 elements. The sequence features of tie recombini ng LINE-1 elements and of the recombination junction site, and possibl e reasons for the more frequent occurrence of unequal homologous recom bination between Aln elements are discussed. (C) 1998 Academic Press L imited.