Mobile elements in the human genome: implications for disease

Abstract

Perhaps as much as two-thirds of the mammalian genome is composed of mobile genetic elements ('jumping genes'), a fraction of which is still active or can be reactivated. By their sheer number and mobility, retrotransposons, DNA transposons and endogenous retroviruses have shaped our genotype and phenotype both on an evolutionary scale and on an individual level. Notably, at least the non-long terminal repeat retrotransposons are still able to cause disease by insertional mutagenesis, recombination, providing enzymatic activities for other mobile DNA, and perhaps by transcriptional overactivation and epigenetic effects. Currently, there are nearly 100 examples of known retroelement insertions that cause disease. In this review, we highlight those genome-scale technologies that have expanded our knowledge of the diseases that these mobile elements can elicit, and we discuss the potential impact of these findings for medicine. It is now likely that at least some types of cancer and neurological disorders arise as a result of retrotransposon mutagenesis.

Figure 1

Types of retroelements implicated in human disease. ENV, envelope; GAG, group specific antigen; HERV, human endogenous retrovirus; kb, kilobase; LTR, long terminal repeat; ORF, open reading frame; POL, polymerase; SINE, short interspersed element; SVA, SINE-R/VNTR/Alu; TPRT, target primed reverse transcription; UTR, untranslated region; VNTR, variable number of tandem repeats. [99]. Black triangles indicate target site duplications.