Alu repeats and human disease.

Alu elements have amplified in primate genomes through a RNA-dependent mechanism, termed retroposition, and have reached a copy number in excess of 500,000 copies per human genome. These elements have been proposed to have a number of functions in the human genome, and have certainly had a major impact on genomic architecture. Alu elements continue to amplify at a rate of about one insertion every 200 new births. We have found 16 examples of diseases caused by the insertion of Alu elements, suggesting that they may contribute to about 0.1% of human genetic disorders by this mechanism. The large number of Alu elements within primate genomes also provides abundant opportunities for unequal homologous recombination events. These events often occur intrachromosomally, resulting in deletion or duplication of exons in a gene, but they also can occur interchromosomally, causing more complex chromosomal abnormalities. We have found 33 cases of germ-line genetic diseases and 16 cases of cancer caused by unequal homologous recombination between Alu repeats. We estimate that this mode of mutagenesis accounts for another 0.3% of human genetic diseases. Between these different mechanisms, Alu elements have not only contributed a great deal to the evolution of the genome but also continue to contribute to a significant portion of human genetic diseases.