An exome panel is a type of genetic test that examines specific parts of an individual’s DNA to identify variations that might be linked to certain health conditions. It offers a broad analysis of genes known to be associated with human diseases. This approach allows for a comprehensive look at the protein-coding regions of a person’s genetic makeup.
Understanding the Exome
The human genome contains an individual’s genetic information, organized into DNA strands. Within this vast genetic code, specific segments called genes provide instructions for building and maintaining the body. Genes are composed of two main parts: exons and introns. Exons are the protein-coding regions, meaning they contain the instructions for producing proteins.
Introns are non-coding regions between exons, typically removed during protein production. The exome is the entire collection of all exons from every gene. While the exome makes up only about 1% to 2% of the entire human genome, it is significant because approximately 85% of known disease-causing genetic variations are found within these protein-coding regions. Focusing on the exome allows for an efficient way to identify many genetic changes linked to various health conditions.
How Exome Panels Are Used
Exome panels are used in clinical settings to diagnose rare genetic disorders, particularly when individuals present with complex or non-specific symptoms that have eluded diagnosis through other means. This testing is often considered for patients who have experienced a “diagnostic odyssey,” a term for undergoing numerous tests without a clear answer. It is especially helpful when a genetic cause is suspected, but the specific gene or genes involved are not immediately clear.
For instance, children with developmental delays, intellectual disabilities, or multiple congenital anomalies are often candidates for exome panel testing. It helps identify the underlying genetic basis for their condition, guiding treatment decisions and providing information about disease progression. The test also benefits individuals with suspected inherited conditions, such such as certain heart conditions or neurological disorders, where a broad genetic screen of known disease-associated genes is beneficial. By analyzing a wide range of genes simultaneously, exome panels uncover genetic variations that might be missed by more targeted gene tests.
The Process of Exome Panel Testing
Exome panel testing begins with a consultation with a healthcare professional, often a genetic counselor or geneticist. During this initial meeting, the patient’s medical history, family history, and the potential implications of the test results are discussed. This ensures the patient understands the test and the information it can provide.
A biological sample, usually blood, is collected from the patient; other tissue types, such as skin cells or cheek swabs, may also be used. DNA is extracted from this sample in the laboratory, and specialized techniques isolate and enrich the exome. Machines then “read” the genetic code of these exonic regions, a process known as sequencing. The sequenced genetic information is then analyzed by bioinformaticians and geneticists who compare it to a standard reference sequence and look for variations that might explain the patient’s symptoms. This analytical phase is complex, taking several weeks to a few months, as it involves careful interpretation of large genetic data.
What Exome Panels Can and Cannot Detect
Exome panels are effective at detecting genetic changes within the protein-coding regions of DNA. They are particularly good at identifying single nucleotide variants (SNVs), which are changes in a single DNA building block, and small insertions or deletions (indels) of a few DNA building blocks. These types of variations within exons are responsible for a large proportion of known genetic disorders. The test provides comprehensive coverage of the protein-coding genes, allowing for the detection of a wide range of disease-causing variants.
However, exome panels have limitations and do not detect all types of genetic variations. They miss large structural variants, such as large deletions, duplications, or rearrangements of DNA segments, which can involve significant portions of chromosomes. Variations in non-coding regions of the genome, including introns and regulatory sequences, are also not covered by exome panels, though these can impact gene expression and lead to disease. Exome panels may not reliably detect mitochondrial DNA variations, certain types of mosaicism (where some cells have a genetic change while others do not), or mutations in highly repetitive DNA regions or those with unusual chemical compositions. While whole genome sequencing (WGS) covers the entire genome, exome sequencing offers a more focused and often more cost-effective approach for identifying variants within the exome.