Genetic Analysis of Patients with Inherited Retinal Dystrophies (IRDs)

Genetic analysis of patients with Inherited Retinal Dystrophies (IRDs) was carried out by performing Whole Genome Sequencing (WGS). The main purpose of this study is to identify simple and complex mutations responsible for IRD in patients. WGS was performed on selected affected and unaffected individuals using the Illumina HiSeqX10. The reads were aligned to human genome 19 (hg19) and variant calling was performed using Genome Analysis Toolkit (GATK). The genotyping quality of single nucleotide variants (SNVs) and indels was assessed using the variant quality score recalibration approach implemented in GATK. Copy number variations (CNVs) were called using Genome STRiP and SpeedSeq. This large set of whole genome sequencing data from different ethnicity can be stored and shared through dbGaP. This data could serve as a source for checking frequencies of variants or the pathogenicity of selected variants in different ethnicities. ]]>
Inclusion: Genetic analysis of patients with IRDs; Patients with diagnoses of inherited retinal dystrophies have been recruited. Available parents affected and unaffected relatives or population controls of different ethnicities were recruited. Exclusion: Patients with a diagnosis of AMD or diabetic retinopathy were excluded. ]]>
Inherited retinal degenerations are a group of eye diseases, which leads to blindness. Mutations in more than 260 genes are known to be involved in causing IRD. Next generation sequencing (NGS) technology is the most effective approach to identify the mutations in patients. Disease gene panels were used at first to screen the most common mutations in patients. Whole exome sequencing is more beneficial in identifying mutations in known and novel genes. Whole genome sequencing (WGS) is the most efficient tool to identify the complex variants in genes known to be associated with retinal degeneration or novel genes. WGS also provides an opportunity to identify complex and de-novo and non-coding causative variants in addition to mutations involving coding regions. Functional evaluation of these candidate variants will validate their role in causing pathology. ]]>