Customizing the Exome
Principal Clinical Scientist,
The introduction of exome analysis provides the opportunity to improve more findings compared to traditional genetic testing approaches and fixed panel-based genomic analyses. Large studies of many families using trio exomes and a genotype first approach have been incredibly powerful tools for gene discovery and identification of pathogenic variants in rare Mendelian disorders. Proband only exomes, however, require different methods of variant filtering which typically involve prioritisation of genes and/or variants based on phenotype.
Eager to realize the benefits of exome testing and streamline laboratory workflows, we evaluated a number of enrichment products before developing a 17Mb SureSelect custom constitutional panel for use in our laboratory.
Combined with an internet browser based system for the referral of cases, which incorporates an algorithm for dynamic gene panel selection using the Human Phenotype Ontology (HPO), we provide an affordable proband only exome service which maximises detection rate and simultaneously minimizes wasted sequencing capacity while avoiding the requirement for continuous redesign and validation of disease-specific gene panels following new evidence.