Gene panel sequencing is a targeted method for analyzing a select group of genes known to be associated with a specific condition or related diseases. This technology examines the DNA sequence of these pre-selected genes to identify variations, also known as mutations, that could be linked to a person’s health. By concentrating only on genes relevant to a particular clinical question, this approach provides a focused and efficient genetic investigation.
This type of testing is highly specific, analyzing anywhere from a few genes to several hundred, depending on the condition. The genes included in a panel are chosen based on established scientific evidence linking them to certain diseases. This targeted nature allows for a deep analysis of the most relevant parts of a person’s genetic code for a given medical concern.
The Gene Panel Sequencing Process
The process for a patient undergoing gene panel sequencing begins with a consultation with a healthcare provider or a genetic counselor. During this meeting, personal and family medical history is reviewed to determine if this testing is appropriate. If the decision is made to proceed, the next step is sample collection, which involves a simple blood draw or a saliva sample.
Once the sample arrives at the laboratory, technicians isolate the DNA from the collected blood or saliva. Using a technology called next-generation sequencing (NGS), the laboratory then focuses on the specific genes included in the ordered panel. This is often achieved through methods like hybridization capture, where probes are used to “pull out” and enrich the DNA from the target genes.
The isolated DNA from these target genes is then sequenced, which means the lab reads the precise order of the DNA building blocks, or nucleotides. This sequence is compared to a standard reference to identify any variations. The process culminates in a detailed report that outlines the findings, which is sent to the healthcare provider to discuss with the patient.
Applications in Medicine
In oncology, gene panel sequencing is frequently used to assess hereditary cancer risk. For instance, hereditary breast and ovarian cancer panels test genes like BRCA1 and BRCA2, providing information that can guide decisions about screening and prevention for individuals and their families. Similar panels exist for other inherited cancer syndromes, such as those associated with colorectal cancer.
In cardiology, gene panels are used to diagnose inherited heart conditions. These can include cardiomyopathies, which affect the heart muscle, or arrhythmias, which cause irregular heartbeats. By identifying the specific genetic cause of a cardiac condition, physicians can better predict the course of the disease and make more informed treatment choices.
The field of neurology also relies on gene panels for diagnosing a wide range of inherited disorders. For conditions like epilepsy or muscular dystrophy, where many different genes can be responsible, a panel can pinpoint the exact genetic cause. This molecular diagnosis is important for understanding a patient’s prognosis and managing their condition. Gene panel sequencing is also used in pharmacogenomics to predict how a person might respond to certain medications, helping to personalize treatment.
Comparison with Other Genetic Tests
Gene panel sequencing is one of several types of genetic tests, each with a different scope of investigation. It is most clearly understood when compared to Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS). A gene panel is the most targeted of the three, focusing on a pre-selected set of genes.
Whole Exome Sequencing casts a much wider net, analyzing the DNA sequences of all protein-coding genes in the genome, known as the exome. The exome accounts for about 1-2% of the entire genome but is where the majority of known disease-causing mutations are found. It provides a broad view of the most functionally relevant parts of the DNA.
Whole Genome Sequencing is the most comprehensive test, analyzing an individual’s entire genetic code, including both protein-coding and non-coding regions. The primary trade-offs between these tests involve scope, cost, and time. Gene panels are less expensive and have a faster turnaround time, but they can only find variants in the genes they are designed to look at. WES and WGS offer a more extensive search but are more costly and generate a larger volume of complex data that requires more in-depth analysis.
Interpreting the Results
The report from a gene panel sequencing test will classify any identified genetic variants into one of three main categories. The first is “Pathogenic” or “Likely Pathogenic,” which indicates that the identified variant is known to be associated with a specific disease. This result can confirm a diagnosis or identify a specific health risk. The second category is “Benign” or “Likely Benign,” meaning the variant is a common and harmless genetic difference that is not associated with disease.
A third, and often more complex, category is “Variant of Uncertain Significance” (VUS). A VUS is a genetic change whose impact on health is not currently known. It is an inconclusive result, meaning there is not enough scientific evidence at this time to classify the variant as either benign or pathogenic. Receiving a VUS result does not mean a person has or will develop a condition; it simply means the significance of that specific genetic change is unclear.
Over time, as more research is conducted and more data becomes available, a VUS may be reclassified to either likely pathogenic or likely benign. This is why ongoing communication with a healthcare provider is important. The role of a genetic counselor is particularly valuable in helping patients understand these results. They can explain what each category means in the context of the individual’s personal and family health history and provide guidance on how to use the information for medical management.