Topic: About Gene Overexpression
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Gene Overexpression: Uses, Mechanisms, and Interpretation
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461
Address for correspondence: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. E-mail: email@example.com
Relevance of overexpression to human health
The lessons learned from overexpression studies have several implications for human health, impacting our understanding of the causes and treatment of diseases. First, there are numerous examples in which human diseases are directly caused by increased gene expression (Shastry 1995; Santarius et al. 2010), sometimes accompanied by gene amplification, highlighting the importance of understanding at least in broad terms the mechanisms by which overexpression can cause mutant phenotypes. Second, even when overexpression does not cause overt diseases, changes in gene expression patterns or levels can contribute to phenotypic variation, diversity, and evolution (Carroll 2008). For example, human copy number variants (CNVs) can cause human familial diseases and are likely to contribute to more complex disease phenotypes (Zhang et al. 2009). The contributions to phenotypic variability by CNVs and noncoding polymorphisms that increase expression levels are only beginning to be explored but will be an important area of future investigation. Third, the successful application of systematic overexpression studies in organisms such as yeasts, Drosophila, and Arabidopsis strongly suggests that analogous systematic overexpression collections of human genes will be valuable basic research tools in cell culture systems to reveal additional therapeutic applications of gene overexpression. The generation of iPS cells (Takahashi and Yamanaka 2006) and the induction of neurons from fibroblasts (Pang et al. 2011) by combinatorial targeted overexpression highlight the application of overexpression to potential therapeutic use. Finally, the realization that overexpression can cause phenotypes, including diseases in humans, accentuates the importance of establishing correct levels of expression in gene therapy strategies. Concerns about integration of gene therapy vectors inadvertently increasing expression of adjacent genes has triggered extensive research into development of retroviral vectors that block increased expression of genes adjacent to the viral integration site (Maier et al. 2010).