The topic of genetics is a vast and complex one. For many, the last time they may have heard terms like genotype, allele, and mutations was in high school biology. Let’s go back to the basics and review some terminology, concepts, and things to consider when deciding whether genetic testing for neurodegenerative disease is right for you.
First things first, inside each of our cells is deoxyribonucleic acid (DNA). Sequences of DNA make up discrete units, called genes.
Within a single gene, hundreds of changes can occur. A person’s unique sequence of DNA is called a genotype. The detectable expression and physical manifestation of a genotype is called a phenotype. Mutations can be inherited or de novo. Inherited mutations are passed down through specific patterns of inheritance (described in more detail here). De novo mutations occur during the process of spontaneous alteration in the development of reproductive cells.
Differences in our genes contribute to what makes each person unique. Often these changes will be called a mutation. However, a gene mutation does not always mean you will have a medical problem. There are three types of genetic variation: (1) normal variation, which is called a benign change (2) pathogenic variation, which causes the gene to no longer work properly, and (3) variations of uncertain significance, which are changes with unknown effects. Not all changes are created equal. If a gene is not working correctly it can cause medical problems. For example, a pathogenic gene variation might mean that proteins are not folding correctly or working correctly, there could be too much protein, not enough protein, wrongly shaped protein, and more.
Another term you might come across is penetrance. Penetrance tells us the chances of having symptoms if you have a disease-causing alteration of a gene. Different genes have different levels of penetrance. For example, if penetrance is 100% then having the mutation means that you will, with certainty, have symptoms.
Now that we know the basics, here are some questions you might ask yourself when considering whether to get tested. Has a mutation been identified in my family? Is there a strong family history of neurodegenerative disease or another neurological disease? What was the disease onset and progression like for me or my family members? How would learning the results of genetic testing benefit me?
When considering genetic testing, it is best to always meet with a genetic counselor. It is a genetic counselor’s job to explain the risks and benefits of testing, what the results could mean for you or your offspring, and its impacts on long-term care and life insurance. They are also there to walk you through any emotional distress related to testing.