Gene duplication: a drive for phenotypic diversity and cause of human disease.
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.
Conrad
Bernard
B
Department of Genetic Medicine & Development, University of Geneva Medical School and Geneva University Hospitals, CH-1211 Geneva 4, Switzerland. bernard.conrad@insel.ch
Antonarakis
Stylianos E
SE
D000818:Animals; D004303:Dosage Compensation, Genetic / Q000502:physiology; D019143:Evolution, Molecular; D018628:Gene Dosage / Q000502:physiology; D020440:Gene Duplication; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology*; D015894:Genome, Human; D006801:Humans; D008954:Models, Biological