Understanding genetics: What are “penetrance” and “expressivity”?

Eyes

When reading about genetics, you may wonder why some people’s eyes are brown while others’ are blue. Why are genetic diseases described with phrases like “not everyone with this variant will develop the condition”? Genetics isn’t always black and white—there are many factors that impact whether or not you might express a trait or condition. The genetics behind your physical appearance and the nuances of disease-risk can be confusing. But if you understand some of the terminology, you can use your DNA to learn about potential disease risks, personal athleticism, dietary intolerances, and more.

Today, we’ll learn about two of the most important terms: penetrance and expressivity. Penetrance describes how likely a person is to present a specific physical trait based on their genetic profile. Traits are physical features that are coded in our DNA, such as eye color and height. Some traits are harder to see, like your blood type and what kind of skeletal muscle fibers you produce. The development of a disease that results from genetic variations is also considered a trait. A classic example of this is breast cancer, in which people who have a variation in a particular gene (like BRCA1) have a higher likelihood of developing cancer. In this case, cancer is the trait. But notice how we wrote “higher likelihood.” That’s because DNA variations affecting the BRCA1 gene increase your risks of getting cancer, but they don’t guarantee it. This is known as incomplete penetrance.

Penetrance is considered incomplete if some people have a particular gene variant that is known to be associated with a disease, yet they never get the disease. Complete penetrance, on the other hand, is when everyone who carries a particular gene variant develops the disease. An easy way to represent this concept is with numbers: suppose 100 people have a disease related gene variant. If all 100 of them end up with the disease, then that gene variant would be considered fully penetrant. But if only 80 of them get the disease within the time frame evaluated, it would be incomplete penetrance.

Why is this important to you? The concept of penetrance can have a huge impact on how you view and respond to your personal genetic results. If you get genetic testing done, you are likely to see terms or phrases relating to penetrance. These terms are used when explaining the likelihood that you may develop a certain trait given your specific genetic results. By way of example, if you carry a gene variant that is associated with cancer and has an 80% penetrance, you may be more inclined to seek regular screening. However, if the gene variant penetrance is only 1%, your response might be quite different.

So if a person’s DNA carries a variation that is associated with a disease and is highly penetrant, does that mean they will get the worst of the disease? Luckily, no. Penetrance is simply a measure of how likely you are to display a trait and says nothing about the extent of the trait’s expression. This is called expressivity, and eye color is a good example of how it works. The color of your eyes is partly determined by the production of a brownish protein called melanin; high levels of melanin cause a person to have brown eye color, while low levels result in blue eyes. This means that even blue-eyed people have traces of brown in their eyes. The key factor here is the magnitude of melanin expression. In this case, brown eye color is fully penetrant because we all have some amount of brown in our eyes, but the expressivity of brown eyes is variable because there are different magnitudes of melanin expression among different people. This same concept can be applied to disease related genes: just because you have a fully penetrant disease does not mean you will present with the most severe form of the disease.

We don’t fully understand yet why there is so much variability in how genes affect people, but we do know that your environment, lifestyle, and other gene variations can all affect how expressive and penetrant a gene might be. Simply because your DNA tells us that you are likely lactose intolerant does not mean you are—but if you are, your symptoms might be so mild that you don’t even notice (an example of variable expressivity).

What does it all mean? For starters, there’s much more to your genetic profile than meets the eye. Beyond the app-based guidance provided by certain products in the Helix marketplace, genetic counselors are a great resource that can help answer your questions. But no matter how you do it, learning more about your DNA can help you make more informed decisions and lead a smarter, healthier life.

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