Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Genome Med. 2013 Oct 11;5(10):84. doi: 10.1186/gm488. eCollection 2013.
Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity. Molecular mechanisms have not been delineated for many retinal diseases, and treatment options are limited. In most instances, genotype-phenotype correlations have not been elucidated because of extensive clinical and genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome, genome, transcriptome and epigenome sequencing, provide novel avenues towards achieving comprehensive understanding of the genetic architecture of RDDs. Whole-exome sequencing (WES) has already revealed several new RDD genes, whereas RNA-Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene regulation and biological networks that are involved in retinal development, aging and disease. In this review, we focus on the genetic characterization of retinal and macular degeneration using NGS technology and discuss the basic framework for further investigations. We also examine the challenges of NGS application in clinical diagnosis and management.
遗传性视网膜退行性疾病（RDD）在遗传方式、潜在遗传缺陷、发病年龄和表型严重程度方面表现出广泛的差异。许多视网膜疾病的分子机制尚未阐明，治疗选择也有限。由于广泛的临床和遗传异质性，大多数情况下尚未阐明基因型-表型相关性。下一代测序（NGS）方法，包括外显子组、基因组、转录组和表观基因组测序，为全面了解 RDD 的遗传结构提供了新途径。全外显子组测序（WES）已经揭示了几个新的 RDD 基因，而 RNA-Seq 和 ChIP-Seq 分析有望揭示参与视网膜发育、衰老和疾病的基因调控和生物网络的新方面。在这篇综述中，我们重点介绍了使用 NGS 技术对视网膜和黄斑变性的遗传特征，并讨论了进一步研究的基本框架。我们还研究了 NGS 在临床诊断和管理中的应用所面临的挑战。
