Human Retrotransposons in Health and Disease

Retrotransposons are highly repetitive and dispersed sequences. These transposable elements have the ability to proliferate via an RNA-mediated copy-and-paste mechanism, called retrotransposition, and belong to several distant subclasses in humans. The Long INterspersed Element-1 (L1 or LINE-1) is the only autonomous transposable element able to generate new copies in the modern human genome. The role of this process as a source of genetic diversity and diseases in humans has been recognized since the late 1980s. However, the advances of deep-sequencing technologies have recently shed new light on the extent of L1-mediated genome variations. They have also led to the discovery that L1 is not only able to mobilize in the germline—resulting in inheritable genetic variations—but can also jump in somatic tissues, such as embryonic stem cells, neuronal progenitor cells, and in many cancers. L1 is also able to mobilize in trans other sequences, leading to the expansion of Alu elements, which belong to another class of repeats, the Short INterspersed Elements (SINEs); or to the formation of processed pseudogenes, which also contribute to genome plasticity. Understanding the link between retrotransposon-mediated structural genomic variation and human phenotypes or diseases has become an intense field of research.