Insertion of a short Alu sequence into the hMSH2 gene following a double cross over next to sequences with chi homology.

Alu repeat sequences and other multiple copy repetitive elements are present throughout the human genome and are active in promoting recombination. It is believed that reverse transcription of transcribed Alu repeats followed by chromosomal integration has been responsible for the wide dispersion and high copy number of these sequences. During studies on the hMSH2 gene we have used RT-PCR to amplify from peripheral blood lymphocytes a cDNA species in which 553 base pairs of hMSH2 cDNA have been deleted to be replaced by a short 36 base pair Alu sequence as a result of a genomic insertion/deletion event. The 36 base pair Alu insert is homologous to a 26 base pair Alu sequence previously implicated in the promotion of recombination and contains the GCTGG motif which is part of the prokaryotic chi sequence. A second chi-like sequence is also located within the deleted hMSH2 region. Both chi-like sequences are located within 4 bp of the two 4-bp regions of cross over containing the insertion/deletion breakpoints. This suggest that a double recombination event has occurred, providing direct evidence for the recombinogenic activity of this Alu element. Furthermore, it suggests that chi-like sequences may define recombination hotspots as in prokaryotes.