Clinical Exome and NGS Panels with Next-Generation Sequencing Technologies

Whole genome, whole exome, and clinical exome sequencing is a laboratory test designed to determine and analyze the sequence of all protein-coding genes in the genome. The goal is to identify the responsible genes and achieve a diagnosis in individuals with a genetic or metabolic/neurometabolic disease who have undergone detailed clinical and laboratory evaluation but remain undiagnosed. Clinical exome analysis can sequence approximately 95% of the exome. Its diagnostic yield is 20-30%.

• Whole Genome Sequencing
• Whole Gene Sequencing
• Gene Panels
• RNA Sequencing

NGS Panels (Next-Generation Sequencing Panels)

Many hereditary disorders are genetically heterogeneous; in other words, pathogenic variants occurring in more than one gene can cause the same genetic disorder (such as Noonan syndrome). Before next-generation sequencing methods, the cost-effective way to test multiple genes was to examine disease-associated genes one by one in sequence. With advances in sequencing techniques, NGS panels that analyze multiple genes simultaneously have been developed and are now widely used in clinical practice.

Advantages of NGS Panels

• Sequencing the genes included in a panel allows a specifically targeted analysis to be performed.
• Sequencing the entire relevant gene increases the reliability of the results.
• Detailed examination of the region of interest can provide higher sensitivity in detecting somatic mosaic variants.
• Variants in targeted non-coding regions can be identified.
• It may include additional analyses for deletions and duplications too large to be detected by sequence analysis.
• Specialized sequence analyses can be applied to distinguish specific genes from highly homologous pseudogenes.
• Because fewer genes and variants are evaluated, results can be interpreted more quickly compared to clinical exome or genome analyses.
• The likelihood of obtaining incidental findings related to diseases outside the suspected phenotype can be reduced.

Advantages of Clinical Exome or Clinical Genome Analyses Over NGS Panels

• The clinician does not need to precisely determine at the outset which diseases and genes should be included in the analysis.
• The co-occurrence of two different genetic disorders in the same individual can be detected.
• Because selecting an appropriate panel is difficult for poorly defined or complex phenotypes, it can provide a broader evaluation.
• Rare diseases or newly discovered genes may not be included in a disease-specific panel; broader analyses can reduce this limitation.
• Panel coverage and clinical sensitivity can vary; clinical exome or genome analysis offers a broader option for re-evaluation.