Gene Duplication: A Drive for Phenotypic Diversity and Cause of Human Disease

Annu Rev Genomics Hum Genet. 2007;8:17-35. doi: 10.1146/annurev.genom.8.021307.110233.


Gene duplication is one of the key factors driving genetic innovation, i.e., producing novel genetic variants. Although the contribution of whole-genome and segmental duplications to phenotypic diversity across species is widely appreciated, the phenotypic spectrum and potential pathogenicity of small-scale duplications in individual genomes are less well explored. This review discusses the nature of small-scale duplications and the phenotypes produced by such duplications. Phenotypic variation and disease phenotypes induced by duplications are more diverse and widespread than previously anticipated, and duplications are a major class of disease-related genomic variation. Pathogenic duplications particularly involve dosage-sensitive genes with both similar and dissimilar over- and underexpression phenotypes, and genes encoding proteins with a propensity to aggregate. Phenotypes related to human-specific copy number variation in genes regulating environmental responses and immunity are increasingly recognized. Small genomic duplications containing defense-related genes also contribute to complex common phenotypes.

Publication types

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

MeSH terms

  • Animals
  • Dosage Compensation, Genetic / physiology
  • Evolution, Molecular*
  • Gene Dosage / physiology
  • Gene Duplication*
  • Gene Expression Regulation, Developmental
  • Genes, Developmental / physiology
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease
  • Genetic Variation / physiology*
  • Genome, Human
  • Humans
  • Models, Biological