Germline genetic testing analyzes an individual’s inherited genetic information to identify changes present in nearly every cell of the body. This type of testing examines DNA passed down from biological parents. It provides insights into a predisposition to certain hereditary health conditions.
What Germline Genetic Testing Is
Germline genetic testing focuses on genetic variations, often called mutations or pathogenic variants, inherited from parents and present in DNA from conception. These changes exist in nearly all body cells, including reproductive cells (sperm or egg), allowing them to be passed to future generations.
This type of testing differs from somatic genetic testing. Somatic mutations are genetic alterations acquired by cells during a person’s lifetime. These changes occur in specific cells, such as cancer cells, and are not present in every body cell. Unlike germline mutations, somatic mutations cannot be passed down to offspring.
Germline variants can arise spontaneously, meaning they are new mutations not present in either parent, or they can be inherited from one or both parents. When a germline mutation occurs in an egg or sperm cell, it can result in the mutation being present in every cell of the offspring’s body. This distinction is important as germline findings have implications for both the individual and their biological relatives.
Why Germline Testing Is Performed
Germline genetic testing is performed for several medical reasons, primarily to identify an inherited predisposition to certain diseases. This includes hereditary cancers, such as those associated with breast, ovarian, colorectal, and pancreatic cancers. Conditions like Lynch syndrome, which increases the risk of several cancers, are also identified through germline testing.
Beyond cancer, germline testing can identify inherited risks for neurological disorders, cardiovascular conditions, and various rare genetic syndromes. Knowing about these inherited risks allows for informed medical management. This can include personalized cancer screening, preventive strategies, and even targeted therapies.
For instance, identifying a germline mutation in genes like BRCA1 or BRCA2 can guide decisions on enhanced surveillance, such as more frequent mammograms or MRI screenings, or risk-reducing surgeries. This information is also important for family members, as it can prompt cascade testing to determine if they also carry the inherited variant, enabling them to pursue their own risk management.
How Germline Testing Works and What Results Indicate
Germline genetic testing typically begins with collecting a biological sample, such as blood, saliva, or a cheek swab. DNA is then extracted and analyzed using next-generation sequencing (NGS). NGS allows laboratories to rapidly sequence many genes simultaneously, looking for specific changes in the DNA sequence.
Test results fall into a few categories. A “positive result” means a pathogenic or likely pathogenic variant was found. This indicates an increased risk for a specific condition, such as a hereditary cancer syndrome. Such a finding can inform medical decisions, including tailored screening protocols, preventive measures, or eligibility for certain targeted therapies.
A “negative result” indicates that no pathogenic or likely pathogenic variants were found in the genes analyzed. It is important to understand that a negative result does not eliminate all risk, as the test may not cover every possible gene or unknown variants. An individual’s personal and family medical history still remains relevant in assessing overall health risks.
Sometimes, a “variant of uncertain significance” (VUS) is reported. A VUS is a genetic change whose clinical importance is not yet fully understood. VUS findings are common, and many are reclassified over time as more data become available. Genetic counseling is important both before and after testing to help individuals understand the potential implications of their results and navigate emotional aspects.