Retrotransposon-derived elements in the mammalian genome: a potential source of disease

The plethora of genomic information gathered by the sequencing of the human and mouse genomes has paved the way for a new era of genetics. While in the past we focused mainly on the small percentage of DNA that codes for proteins, we can now concentrate on the remainder, i.e. the noncoding sequences that interrupt and separate genes. This portion of the genome is made up, in most part, of repetitive DNA sequences including DNA transposons, long terminal repeat (LTR) retrotransposons, LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements). Some of these elements are transcriptionally active and can transpose or retrotranspose around the genome, resulting in insertional mutagenesis that can cause disease. In these cases, insertions have occurred in the coding sequence. However, recent evidence suggests that the main effect of these elements is their ability to influence transcription of neighbouring genes. The elements themselves contain promoters that can initiate transcription of flanking genomic DNA. Furthermore, they are susceptible to epigenetic silencing, which is often stochastic and incomplete, resulting in complex patterns of transcription. This review discusses some diseases in both human and mouse that are caused by these repetitive elements.