Gene dosage effects: nonlinearities, genetic interactions, and dosage compensation.
Gene dosage effects: nonlinearities, genetic interactions, and dosage compensation.
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DOI：
10.1016/j.tig.2013.04.004
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发表时间：
2013-07
期刊：
影响因子：
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通讯作者：
R. Veitia;S. Bottani;J. Birchler
中科院分区：
文献类型：
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作者：
R. Veitia;S. Bottani;J. Birchler
高通量基因组分析表明，许多突变，包括功能丧失（LOF）突变，存在于患病和健康个体中。由于缺失、重复和LOF突变引起的基因剂量效应为探索寡基因和多基因遗传提供了途径。在这里，我们专注于几种机制，介导基因剂量效应和分析多个基因产物之间的生物化学相互作用的非线性关系连接基因型和表型的来源。我们还探讨了补偿基因剂量效应的潜在机制。理解这些问题对于理解为什么携带一些破坏性突变的个体可能会严重患病，而其他携带数十个潜在有害突变的个体可能看起来相当健康至关重要。
High-throughput genomic analyses have shown that many mutations, including loss-of-function (LOF) mutations, are present in diseased as well as in healthy individuals. Gene dosage effects due to deletions, duplications, and LOF mutations provide avenues to explore oligo- and multigenic inheritance. Here, we focus on several mechanisms that mediate gene dosage effects and analyze biochemical interactions among multiple gene products that are sources of nonlinear relations connecting genotypes and phenotypes. We also explore potential mechanisms that compensate for gene dosage effects. Understanding these issues is critical to understanding why an individual bearing a few damaging mutations can be severely diseased, whereas others harboring tens of potentially deleterious mutations can appear quite healthy.