Although the current practice of analysing defined gene panels for a specific disease has great utility, it is of limited benefit when a condition is not well defined. By generating the sequence data for the whole exome or genome, clinicians and researchers have the opportunity to look more broadly, but there are concerns about incidental findings and the issues they raise. Using virtual gene panels offers the benefits of both approaches. However, argues Mike Furness of Congenica, there is considerable variation in the way that gene panels are created and analysed. Mike will be discussing this at the Next Generation Dx Summit on Thursday 25th August 2016.
“Knowing which analysis is the most helpful in unravelling the genetic cause of a patient’s symptom is a complex task with both technical and ethical issues,” comments Mike Furness of genomics analysis company Congenica. “Whole exome and genome analysis brings many benefits but it can also reveal variations where pathogenicity is not yet understood.”
Currently, the majority of next generation DNA sequencing-based genetic testing uses a physical gene panel to capture a set of specific genes thought to be at the root of the observed clinical phenotype. This approach is useful where strong gene candidates have been confidently linked to the phenotype observed.
Gene panels, however, often fall short in the diagnosis of rare diseases with complex phenotypes; in these cases, gene panels can be too restricted to be able to pinpoint the cause of the disorder. Whole exome sequencing enables the interrogation of all genes that code for proteins, providing a comprehensive genome wide analysis that significantly increases the diagnostic yield for complex cases.
A key advantage of using whole exome sequencing is the ability to design and apply virtual gene panels. Typically, analysis will begin with a set of known genes associated with the phenotype of interest. If this proves negative, further genes can be added to the panel or the entire exome can be “opened up” to search for novel candidate genes. The virtual approach also provides a mechanism to exclude the analysis of certain genes.
Mike Furness says current practice needs to change to enable data sharing; this ensures the aggregated data used in diagnoses is shared with other practitioners so that the selected virtual gene panels are robust and consistent for clinical diagnosis.
“As more knowledge emerges, we are able to further improve the tools available. This is a result of very close working relationships with partners using our clinical interpretation platform Sapientia™".
Sapientia™ equips clinicians and scientists with the tools to interpret mutations found in exomes and genomes and links them to the symptoms displayed by the patient. It provides a list of potential disease-causing variants that can be assigned pathogenicity by users.
“We anticipate fewer requirements for virtual gene panels in the near future, but in the short term we need to achieve greater consensus on which genes to include, and the evidence behind these.”
Mike Furness of Congenica, presents ‘Sapientia™ – faster, more accurate diagnosis using a data sharing platform’ at 9.30am on Thursday 25th August 2016 at Harnessing the Power of Genomic Information, Cambridge Healthtech Institute’s second annual NGS diagnosis: data considerations, annotation and interpretation conference which is a strand of the Next Generation Dx Summit.