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.

中文翻译：

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基因复制：驱动表型多样性和人类疾病的原因。

基因复制是驱动遗传创新的关键因素之一，即产生新的遗传变异。尽管全基因组和节段重复对物种间表型多样性的贡献已广为人知，但对单个基因组中小规模重复的表型谱和潜在致病性却鲜有研究。这篇评论讨论了小规模重复的性质以及此类重复产生的表型。由重复引起的表型变异和疾病表型比以前预期的更加多样化和广泛，并且重复是与疾病相关的基因组变异的主要类别。致病性复制特别涉及具有相似和不相似的过表达和表达不足表型的剂量敏感基因，以及编码具有聚集倾向的蛋白质的基因。人们越来越认识到与调节环境响应和免疫力的基因中人类特异性拷贝数变异有关的表型。包含防御相关基因的小基因组重复也有助于复杂的常见表型。