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Retrotransposal integration of mobile genetic elements in human diseases Miki YJ Hum Genet 1998[]; 43 (2): 77-84Approximately one-third of the mammalian genome is composed of highly repeated DNA sequences, of which the two major families, the long and short inter-spersed nucleotide elements (LINEs and SINEs), are represented in humans by L1 and Alu elements respectively. Both 'types of element are considered to be retrotransposable and to play significant roles 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 duplications of various lengths and contain 3' polyA tracts, common characteristics of retrotransposal integration. Retrotransposal integrations of Alu and L1 sequences into biologically important genes appear to play significant roles in some human diseases. Most of the inserted sequences that cause human diseases seem to belong to one or a few subsets of each type of retrotransposon, suggesting that only a few active elements can function as templates for retrotransposition. Integrations 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 integration may be a general mechanism of mutation in humans.|*Mutagenesis, Insertional[MESH]|*Retroelements/genetics[MESH]|Animals[MESH]|Base Sequence[MESH]|DNA Mutational Analysis[MESH]|DNA/genetics[MESH]|Evolution, Molecular[MESH]|Genetic Diseases, Inborn/*genetics[MESH]|Humans[MESH]|Mammals/genetics[MESH]|Mice[MESH]|Mice, Mutant Strains[MESH]|Molecular Sequence Data[MESH]|Neoplastic Syndromes, Hereditary/genetics[MESH]|Oncogenes[MESH]|Rats[MESH]|Rats, Mutant Strains[MESH]|Repetitive Sequences, Nucleic Acid[MESH]|Retroviridae/genetics[MESH]|Sequence Alignment[MESH]|Sequence Homology, Nucleic Acid[MESH]|Virus Integration[MESH] |
