Gene panel sequencing

Gene panels are collections of genes that have been grouped for testing, enabling simultaneous sequencing of all the genes known to cause a particular disease, syndrome or phenotype. They may include anything from two to over 1,000 genes. Examples include gene panels for ‘intellectual disability’, ‘monogenic diabetes’ and ‘inherited ovarian cancer’.

How is gene panel sequencing done?

Gene panel sequencing is usually done using massively parallel sequencing technology (sometimes called next-generation sequencing).

There are two types of gene panels:

• Targeted panel sequencing: where data are only generated for genes on the panel. During the preparation of patient DNA for sequencing, DNA from the genes on the panel is enriched through hybridisation probe capture or polymerase chain reaction (PCR) amplification. DNA from other parts of the patient’s genome are not tested.
• Virtual panels applied to data from whole exome sequencing (WES) or whole genome sequencing (WGS). In this case, although sequencing data are generated for all genes, only the genes in the virtual panel(s) relevant to the patient’s condition are analysed.

• Gene panel sequencing is frequently used in clinical diagnostics to identify a genetic cause of rare disease.
• Compared to either sequential single gene sequencing, or to more extensive WES or WGS, it is fast and cost-effective.
• Focusing on a gene panel limits the number of variants requiring interpretation, and results in fewer variants of uncertain significance (VUS) being identified.
• Targeted panel sequencing can allow for deeper sequencing (that is, more reads covering the same region of the genome) than WES or WGS. This enables more sensitive detection of mosaicism for conditions in which mosaicism is expected (for example, segmental overgrowth or mosaic skin disorders).
• Where a virtual panel is used, future reanalysis of data may be possible for patients in whom no variants are initially found. In this way, additional genes associated with a disease could be checked for variants over time.
• Exon-level copy number variants can be detected, alongside single nucleotide variants and small insertions/deletions.

Limitations and challenges of gene panel sequencing include:

• It will not identify novel causative genes as it is limited to those genes already known to cause the condition or phenotype.
• Once a gene panel has been designed it can be technically challenging to add new genes as they are discovered.
• It will not detect structural rearrangements or copy number variants (unlike WGS).

For a summary table comparing the advantages and disadvantages of the different approaches to gene sequencing (gene panel/WES/WGS), view the Knowledge Hub article, Different approaches to gene sequencing.

• Gene panels may include anything from two to over 1,000 genes.
• Gene panels can be either targeted or virtual. Targeted panels only generate data for genes on the panel, while virtual panels are applied to WES or WGS data to only analyse data from the genes on the panel.
• Gene panel sequencing is often used in clinical diagnostics to identify a genetic cause of rare disease.

For clinicians

• Association for Clinical Genetic Science: Practice guidelines for Targeted Next Generation Sequencing Analysis and Interpretation (PDF, 13 pages)
• Genomics England: PanelApp
• NHS England: National Genomic Test Directory and eligibility criteria
• Online Mendelian Inheritance in Man: Catalogue of all known disease-causing genes

For patients

• European Society of Human Genetics: A guide to genetic tests that are used to examine many genes at the same time (PDF, seven pages)