Repetitive Elements and Human Disorders

Abstract

Repetitive sequences, consisting largely of transposable elements (TEs), comprise over 50% of the mammalian genome. Ongoing proliferation of human TEs results in a significant level of disease‐causing mutations. More frequently than insertional mutagenesis, TEs participate in nonallelic recombinations that generate both germ‐line and somatic mutations. Further exacerbating the deleterious nature of TEs, the protein products of some autonomous elements have been demonstrated to generate double‐stranded deoxyribonucleic acid (DNA) breaks, which have themselves been established as potent inducers of genetic instability. Other repetitive genomic sequence, such as segmental duplications and microsatellites (particularly triplet repeats), also promote genetic instability resulting in disease phenotypes.

Transposable Elements Cross Kingdom Boundaries and Contribute to Inflammation and Ageing

“…For example, the bacterial IS‐5 like transposon has transferred into bdelloid rotifers, though is transcriptionally inactive, and there are a number of other examples of rapid non‐functionalization after HTT, either through pseudo gene formation, DNA deletion, or inhibition of transcription . Even when inactive, TEs can be deleterious by providing a substrate for ectopic recombination, leading to chromosomal rearrangements and genomic instability, further supporting the idea that HTT into somatic tissues is a catalyst for genome instability that could drive somatic dysfunction and ageing …”