Abstract
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.
Highlights
Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity
The vertebrate retina consists of a retinal pigment epithelium (RPE) monolayer, Müller glial cells, and six major types of neurons (Figure 1a) [1,2]
The loss of peripheral vision - for example, in retinitis pigmentosa (RP) - generally starts with rod dysfunction or death that is followed by cone degeneration
Summary
Whole exome/genome/ candidate exome capture filtering is required to prioritize the candidate disease genes. Profiling of alternative transcripts In humans, a majority of genes (>90%) undergo alternative splicing to generate tissue-specific and functionally diverse protein isoforms [63]. Retina-specific RNA or transcriptome profiling provides an excellent opportunity to identify novel functionally relevant transcripts. Expression in relevant tissues - RNA-seq Implicated in disease-related biological pathways Binding sites for transcription factors - ChIP-seq. Non-coding RNA ncRNAs appear to play prominent and diverse roles in normal development, physiology, and disease. SNP profiling Genetic variations within the transcribed (coding or noncoding) regions of the genome can alter the expression or function of the encoded sequence. RNA-Seq can provide profiles of genetic variants in both the quasicomplete set of transcribed genes (mRNAs) and ncRNAs in a cost-effective manner and without the need for target-probe hybridization, a necessary but inefficient step in capture-based methods. RNA-Seq should be applied with caution, as it is possible to miss variants that result in the loss of a gene product
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
