Retroelements in human disease

Gene. 2013 Apr 15;518(2):231-41. doi: 10.1016/j.gene.2013.01.008. Epub 2013 Jan 17.


Retroelements are an abundant class of noncoding DNAs present in about half of the human genome. Among them, L1, Alu and SVA are currently active. They "jump" by retrotransposition, shuffle genomic regions by 5' and 3' transduction, and promote or inhibit gene transcription by providing alternative promoters or generating antisense and/or regulatory noncoding RNAs. Recent data also suggest that retroelement insertions into exons and introns of genes induce different types of genetic disease, including cancer. Retroelements interfere with the expression of genes by inducing alternative splicing via exon skipping and exonization using cryptic splice sites, and by providing polyadenylation signals. Here we summarize our current understanding of the molecular mechanisms of retroelement-induced mutagenesis which causes fifty different types of human disease. We categorize these mutagenic effects according to eleven different mechanisms and show that most of them may be explained either by traditional exon definition or transcriptional interference, a previously unrecognized molecular mechanism. In summary, this review gives an overview of retroelement insertions in genes that cause significant changes in their transcription and cotranscriptional splicing and show a remarkable level of complexity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Gene Expression
  • Genetic Diseases, Inborn / genetics*
  • Genetic Variation
  • Genome, Human
  • Humans
  • Mutation
  • Polyadenylation
  • Promoter Regions, Genetic
  • RNA Splice Sites
  • RNA Splicing
  • Retroelements / genetics*
  • Transcription, Genetic


  • RNA Splice Sites
  • Retroelements