INTERETHNIC POLYMORPHISM OF EWS INTRON-6 - GENOME PLASTICITY MEDIATEDBY ALU RETROPOSITION AND RECOMBINATION

The EWS gene has been identified as being systematically translocated in Ewing's sarcoma. In order to ascertain the basis of a marked intere thnic difference in the incidence of Ewing's sarcoma, intron 6 of EWS, which is located near the translocation breakpoint region (EWSR1), wa s characterized. Sequence analysis of the entire intron 6 region revea led a very high density of Alu elements. Most of these Alu sequences c ould be classified in previously described subfamilies, facilitating d elineation of an evolutionary model that involves successive retroposi tion events. According to this model, the EWS intron 6 region progress ively expanded until about 5 million years ago. More recently (10(5) y ears ago), in part of the human population, the size of this region de creased by over 50% as the result of a homeologous recombination betwe en two Alu sequences, which removed 2480 bp. This rare allele has only been observed in individuals of African origin, a population that is characterized by the lowest incidence of Ewing's sarcoma.