Conrad Bernard, Antonarakis Stylianos E
Department of Genetic Medicine & Development, University of Geneva Medical School and Geneva University Hospitals, CH-1211 Geneva 4, Switzerland.
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.
基因复制是推动基因创新（即产生新的基因变体）的关键因素之一。尽管全基因组复制和片段复制对物种间表型多样性的贡献已得到广泛认可，但个体基因组中小规模复制的表型谱和潜在致病性却较少被探索。本综述讨论了小规模复制的本质以及此类复制所产生的表型。由复制引起的表型变异和疾病表型比以前预期的更加多样和广泛，并且复制是一类主要的与疾病相关的基因组变异。致病性复制尤其涉及剂量敏感基因，这些基因具有相似和不同的过表达和低表达表型，以及编码易于聚集的蛋白质的基因。与调节环境反应和免疫的基因中人类特异性拷贝数变异相关的表型越来越受到认可。包含防御相关基因的小基因组复制也促成了复杂的常见表型。
