Li Mingyao, Zauhar Randy J, Grazal Clare, Curcio Christine A, DeAngelis Margaret M, Stambolian Dwight
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Department of Chemistry and Biochemistry, The University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Hum Mol Genet. 2017 Aug 1;26(R1):R68-R74. doi: 10.1093/hmg/ddx219.
Recent Genome-wide Association Studies (GWASs) for eye diseases/traits have delivered a number of novel findings across a diverse range of diseases, including age-related macular degeneration (AMD), glaucoma and refractive error. However, despite this astonishing rate of success, the major challenge still remains to not only confirm that the genes implicated in these studies are truly the genes conferring protection from or risk of disease but also to define the functional roles these genes play in disease. Ongoing evidence is accumulating that the single nucleotide polymorphisms (SNPs) used in GWAS and fine mapping studies have causal effects through their influence on gene expression rather than affecting protein function. The biological interpretation of SNP regulatory effects for a tissue requires knowledge of the transcriptome for that tissue. We summarize the reasons to characterize the complete retinal transcriptome as well as the evidence to include an assessment of differences in regional retinal expression.
近期针对眼部疾病/特征开展的全基因组关联研究（GWAS）在多种疾病中取得了一系列新发现，包括年龄相关性黄斑变性（AMD）、青光眼和屈光不正。然而，尽管取得了惊人的成功，但主要挑战依然存在，不仅要确认这些研究中涉及的基因确实是赋予疾病保护或风险的基因，还要确定这些基因在疾病中发挥的功能作用。越来越多的现有证据表明，GWAS和精细定位研究中使用的单核苷酸多态性（SNP）通过影响基因表达而非蛋白质功能产生因果效应。对于一个组织而言，SNP调控效应的生物学解释需要了解该组织的转录组。我们总结了表征完整视网膜转录组的原因以及纳入视网膜区域表达差异评估的证据。
