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Next-generation sequencing strategies have increased the proportion of resolved diagnoses for several IRDs.

Researchers based at the School of Genetics & Microbiology, Trinity College, Dublin, have reported significant progress on next-generation sequencing (NGS) applications on a range of inherited retinal degenerations (IRDs).  Researchers have identified that a genetic diagnosis and testing from NGS data may now be able to define more accurate diagnoses and prognoses, giving valuable genetic counselling support, including further carrier testing and prenatally screening.  According to the studies on IRD genetics research, investigators have commented that, “we are now in the age of genomic medicine, where genetic evidence can often provide precise and robust diagnoses”


Next-generation sequencing (NGS) applications are now well established around the globe.  From a recent count, there are almost 20 currently active government-funded national genomic projects working around the world. IRDs have an estimated prevalence of 1 in 4,000 and therefore, in a global population of ~7.8bn, there may be an estimated 1.95 million IRD patients. To maximise the detection of IRD-causing mutations, several NGS strategies have been identified including: targeted gene panels for IRD phenotypes, whole-exome sequencing (WES), whole-gene sequencing (GS), whole-genome sequencing (WGS) and further bespoke methods such as structural variant (SV) detection and copy number variant detection (CNV).  Dependent on the specifics, either a professional genetic counsellor, and/ or a retinal physician, will guide the particular history and clinical characteristics for individual patients and this will use the information to define which NGS option is suitable.  Whole-exome sequencing (WES) covers protein-coding exons however, this covers only 1% of the genome, while whole-genome sequencing (WGS) covers practically all nucleotides, providing a more comprehensive account.  Book-ended between these strategies, targeting sequencing (TS) captures the smallest amount of genetic information, using a customisable approach; while whole-gene sequencing (GS) captures exonic, intronic and 5’ and 3’ regulatory regions assessing within a target gene of interest.  In terms of the economics of NGS costs, a UK study in 2018 estimated that costs range from $555 to $5,165 for WES and from $1,906 to $24,810 for WGS.


Clinical practice now appears to be capable of resolving an increasing proportion of NGS outcomes, defining specific mutations and further specifying diagnoses within relevant genes and correlated to a patient’s phenotype. In concluding from the significant data, researches have additionally commented that “advances in technologies related to clinical phenotyping” may now be “augmented by machine-learning-based algorithms”. This now points to the direction for travel enhancing IRD screening and further support the “development of national databases and genomics strategies to develop services and enhance clinical genetics collaborations nationally and internationally”.