尚未找出原因的genetic disorders可以从这个角度找找原因

Structural Variation of Alu Element and Human Disease

1. Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ∼10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes.
2. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery.
3. The ‘master gene’ model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes.
4. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them.
5. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder.
6. Alu elements are associated with approximately 0.1% of human genetic disorders.
7. Alus are transcribed by RNA polymerase (Pol) III and are inserted back into the genome with the help of autonomous LINE retroelements.
8. Since Alu elements are preferentially located near to or within gene-rich regions, they can affect gene expression by distinct mechanisms of action at both DNA and RNA levels.
9. Alu elements are pervasively involved in gene regulation

Reference.

1. Songmi Kim, Chun-Sung Cho, Kyudong Han, Jungnam Lee.Genomics Inform 2016;14(3):70-77. Structural Variation of Alu Element and Human Disease.
2. Ling-Ling Chen and Li Yang. Trends in Cell Biology, July 2017, Vol. 27, No. 7. ALUternative Regulation for Gene Expression.