RETROTRANSPOSAL INTEGRATION OF MOBILE GENETIC ELEMENTS IN HUMAN-DISEASES

Approximately one-third of the mammalian genome is composed of highly repeated DNA sequences, of which the two major families, the long and short interspersed nucleotide elements (LINEs and SINEs), are represen ted in humans by L1 and Alu elements respectively. Both types of eleme nt are considered to be retrotransposable and to play significant role s in genomic function and evolution. The majority of inserted elements are truncated and often rearranged relative to full-length elements; usually, such retrotransposed sequences are flanked by target-site dup lications of various lengths and contain 3' polyA tracts, common chara cteristics of retrotransposal integration. Retrotransposal integration s of Alu and L1 sequences into biologically important genes appear to play significant roles in some human diseases. Most of the inserted se quences that cause human diseases seem to belong to one or a few subse ts of each type of retrotransposon, suggesting that only a few active elements can function as templates for retrotransposition. Integration s observed in oncogenes and in tumor suppressor genes may participate in carcinogenesis by altering the activity of the affected genes. The exact mechanism of these events is unclear; however, retrotransposal i ntegration may be a general mechanism of mutation in humans.