Transposable elements in human genetic disease

Transposable elements are abundant in the human genome, and great strides have been made in pinpointing variations in these repetitive sequences using whole-genome sequencing. Now, the focus is shifting to understanding their expression and regulation, and the functional consequences of their insertion and retention in the genome over time. Whereas transposable element insertions have been known to cause human genetic disease since the 1980s, the scope of their contributions to heritable phenotypes is now starting to be uncovered. Here, we review the many ways human retrotransposons contribute to genome function, their dysregulation in diseases including cancer and how they affect genetic disease. Whole-genome sequencing efforts have driven our understanding of transposable elements as a source of genetic variation and the focus is now shifting to understanding their expression and regulation. This Review summarizes the possible functional consequences of transposable element insertion and retention in the genome over time, with a focus on how mobile elements cause disease.