Structural variation mutagenesis of the human genome: Impact on disease and evolution

Environ Mol Mutagen. 2015 Jun;56(5):419-36. doi: 10.1002/em.21943. Epub 2015 Apr 17.


Watson-Crick base-pair changes, or single-nucleotide variants (SNV), have long been known as a source of mutations. However, the extent to which DNA structural variation, including duplication and deletion copy number variants (CNV) and copy number neutral inversions and translocations, contribute to human genome variation and disease has been appreciated only recently. Moreover, the potential complexity of structural variants (SV) was not envisioned; thus, the frequency of complex genomic rearrangements and how such events form remained a mystery. The concept of genomic disorders, diseases due to genomic rearrangements and not sequence-based changes for which genomic architecture incite genomic instability, delineated a new category of conditions distinct from chromosomal syndromes and single-gene Mendelian diseases. Nevertheless, it is the mechanistic understanding of CNV/SV formation that has promoted further understanding of human biology and disease and provided insights into human genome and gene evolution. Environ. Mol. Mutagen. 56:419-436, 2015. © 2015 Wiley Periodicals, Inc.

Keywords: DNA replication; chromosome biology; copy number variant; recombination; structural variant.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Evolution, Molecular
  • Gene Dosage
  • Genetic Predisposition to Disease*
  • Genome, Human / genetics*
  • Genomic Structural Variation*
  • Humans
  • Mutagenesis*