De novo mutations in human genetic disease

Nat Rev Genet. 2012 Jul 18;13(8):565-75. doi: 10.1038/nrg3241.


New mutations have long been known to cause genetic disease, but their true contribution to the disease burden can only now be determined using family-based whole-genome or whole-exome sequencing approaches. In this Review we discuss recent findings suggesting that de novo mutations play a prominent part in rare and common forms of neurodevelopmental diseases, including intellectual disability, autism and schizophrenia. De novo mutations provide a mechanism by which early-onset reproductively lethal diseases remain frequent in the population. These mutations, although individually rare, may capture a significant part of the heritability for complex genetic diseases that is not detectable by genome-wide association studies.

Publication types

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

MeSH terms

  • Autistic Disorder / genetics
  • Female
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Genome
  • Germ Cells
  • Humans
  • Intellectual Disability / genetics
  • Male
  • Mutation*
  • Schizophrenia / genetics
  • Sequence Analysis, DNA / methods