Duplication hotspots, rare genomic disorders, and common disease

Curr Opin Genet Dev. 2009 Jun;19(3):196-204. doi: 10.1016/j.gde.2009.04.003. Epub 2009 May 22.


The human genome is enriched in interspersed segmental duplications that sensitize approximately 10% of our genome to recurrent microdeletions and microduplications as a result of unequal crossing over. We review the recent discovery of recurrent rearrangements within these genomic hotspots and their association with both syndromic and nonsyndromic diseases. Studies of common complex genetic disease show that a subset of these recurrent events plays an important role in autism, schizophrenia, and epilepsy. The genomic hotspot model may provide a powerful approach for understanding the role of rare variants in common disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autistic Disorder / genetics
  • Chromosome Deletion*
  • Epilepsy / genetics
  • Gene Duplication*
  • Genetic Diseases, Inborn / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human / genetics*
  • Humans
  • Models, Genetic
  • Schizophrenia / genetics