Huang Qingyang
College of Life Sciences, Central China Normal University, Wuhan 430079, China.
J Genet Genomics. 2015 Mar 20;42(3):87-98. doi: 10.1016/j.jgg.2015.02.001. Epub 2015 Feb 13.
Genome-wide association studies (GWASs) have identified thousands of genes and genetic variants (mainly SNPs) that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation of these SNPs and genes action are the next major challenge. It has been well established that SNPs altering the amino acids of protein-coding genes can drastically impact protein function, and play an important role in molecular pathogenesis. Functions of regulatory SNPs can be complex and elusive, and involve gene expression regulation through the effect on RNA splicing, transcription factor binding, DNA methylation and miRNA recruitment. In the present review, we summarize the recent progress in our understanding of functional consequences of GWAS-associated non-coding regulatory SNPs, and discuss the application of systems genetics and network biology in the interpretation of GWAS findings.
全基因组关联研究（GWAS）已经鉴定出数千个导致人类复杂疾病的基因和遗传变异（主要是单核苷酸多态性，SNPs）。对这些SNPs和基因作用进行功能表征和机制阐释是下一个重大挑战。众所周知，改变蛋白质编码基因氨基酸的SNPs可显著影响蛋白质功能，并在分子发病机制中起重要作用。调控性SNPs的功能可能复杂且难以捉摸，涉及通过影响RNA剪接、转录因子结合、DNA甲基化和miRNA募集来调控基因表达。在本综述中，我们总结了在理解GWAS相关非编码调控性SNPs功能后果方面的最新进展，并讨论了系统遗传学和网络生物学在解释GWAS研究结果中的应用。
