If DNA is our body’s instructions for how to grow, develop, and function, then a change in these instructions must be bad, right?
Turns out, not so much. In fact, we all have changes in our DNA. The trick is, not all DNA changes are the same. In fact, they’re not always harmful.
In a previous article, I discussed how a genetic testing lab can find a change in one or more of our genes, but not be sure whether the change is harmful and causes disease, based on existing information. This is called a variant of uncertain significance (VUS or VOUS). I also discussed some of the steps that a lab might take to learn more about these changes. But how is a VUS different than other gene changes, like a mutation or polymorphism?
What is a mutation?
Technically, a mutation is any change in a gene’s DNA sequence (spelling) that isn’t considered normal. This implies that each gene has a normal DNA sequence and the mutation changes this sequence from normal to abnormal. Think of it like a spelling error, one that can confuse the instructions within the gene. A mutation is most often used to describe a change that is associated with a genetic disease, which most people may not have.
But here’s the truth: Everyone carries perhaps a dozen different mutations and many of us have no idea what they are. We’re all mutants! Carrying a gene mutation may never cause a health problem. In fact, sometimes it is protective – did you know that being a carrier for the gene mutation that causes sickle-cell anemia is often seen in people whose families originate in tropical parts of the world (such as sub-Saharan Africa, Italy, India, and Saudi Arabia)? Turns out being a carrier helps protect us against malaria… a disease that is common in tropical areas.
What is a polymorphism?
Now, on to gene polymorphisms. A polymorphism is a term used to describe different forms of a gene that are common within the population, but do not generally cause disease. It’s like having different spellings for the same word, but they mean the same thing (think of spelling the word as “color” instead of “colour”, which is often the case outside the U.S.). As scientists have delved into the intricacies of the human genome, we’ve learned that there can be a lot of variation in the gene sequences that contain instructions for specific proteins in our bodies. Some types of genetic variation will change the spelling but not how the protein it codes for works, while other variations can change the protein just enough to alter what it is supposed to do.
For example, there are many polymorphisms in the CYP2C9 gene in humans. This is a gene that provides instructions to build an enzyme in the liver that usually breaks down chemical compounds in the body, including medicines we may need to take. Although these CYP2C9 polymorphisms make enzymes that are basically the same sequence and structure as the usual form of the gene, the small changes in sequence can influence how we break down specific drugs used to prevent blood clots (like warfarin) and reduce inflammation (like ibuprofen). Knowing this type of information can be very valuable to doctors when determining which medication to prescribe to a patient and the right dosage. In fact, there is an entire field of genetics called pharmacogenomics that considers these polymorphisms and their influence on how drugs are broken down (metabolized).
When it comes down to it, all polymorphisms are mutations but not all mutations are polymorphisms.
Why is this important?
The reason that I wanted to make the distinction between these concepts is that it’s important to know what a specific test is designed to study. We live in a world where the ability to order genetic testing is increasingly available, even from the comfort of your home. Many people are familiar with companies that provide direct-to-consumer (DTC) testing, such as 23andMe and Ancestry.com. However, people receiving these test results often misinterpret them because they are unaware of the differences between disease-causing gene mutations and polymorphisms that may be associated with a (sometimes slightly) higher risk of certain diseases.
DTC genetic testing is such a big topic in the field of genetics, that it’s one that I’d like to touch on next month! Stay tuned!
Source: Genetics Home Reference. (2015). CYP2C9 gene. Retrieved September 05, 2017, from https://ghr.nlm.nih.gov/gene/CYP2C9#