Just Enough Genetics To Understand Your Variant
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May 2024
Issue #31

Thanks to Mark Hicks for this illustration

Just Enough Genetics to Understand Your Variant:
Genes and Mutations

This is the first part in a series about the genetics behind variants that increase disease risk. Share this simplified information with your family members who have questions about genes or inheritance. If you'd like a certain topic covered in a future part of this series, let us know.

What is a gene?

A gene is a tool in a system called DNA, which produces proteins. The system generates over 100,000 proteins that work together to make your body function, doing jobs from carrying oxygen to moving muscles. When you eat protein, your body breaks it into pieces, and DNA helps reassemble those pieces into your own proteins.

Each protein has a particular job and is made with a specific gene. For example, a gene called LDLR makes a protein called an LDL receptor that transports cholesterol in the blood. A gene called BRCA1 makes a protein that helps repair damaged DNA and prevent tumors, among other tasks. Your DNA contains all the genes to make the complete set of proteins your body uses. In fact, it has two copies of most genes. You inherit one copy from each of your biological parents.

Your mother has two of each gene, too—one from each of her parents. She passed on only one to you. So did you get your LDLR gene from your grandfather or your grandmother? It could be either. You have a 50% chance of inheriting each copy. You have the same random chance when you inherit genes from your father, so your DNA contains a mix of genes from all four grandparents.

If both copies of a gene make the same protein, does it matter which grandparents you got them from?

Even though your copies of each gene produce the same protein, the versions of the gene are different.

The gene a child gets isn’t always an exact duplicate of their parent’s. The inheritance process can go wrong. The gene may be missing sections or have extra parts. These changes are called mutations. Once a person inherits a changed version of a gene, their children have a 50% chance of inheriting it, like any other gene. The versions, or variants, can be passed down for generations. 

All your genes are likely to have changed at some point. The BRCA1 variant you inherit from your mother may have mutated 10 generations ago, while the BRCA1 variant from your father may have a separate mutation from 15 generations ago. Because the genes are not the same, the proteins they make may not be the same.

Most changes are not a big deal. Both proteins do their job just fine. Even if one version of a protein doesn’t work perfectly, you have backup—the other version picks up its slack. Mutations can even be good because they make people individuals. Every person's DNA has a unique legacy of changes. The proteins in one person don’t do their jobs exactly the same as the proteins in another person, so you don’t look or act like anyone else.

However, every once in a while, a variant is so mutated that its protein is terrible at its job. The protein does its best, but it’s likely to miss something important. A variant that makes this kind of protein is a pathogenic variant.

When someone says their cancer risk is high because they have “the BRCA1 gene,” they mean that one of their copies of the BRCA1 gene is a pathogenic variant.

If you have a pathogenic variant, will you get cancer or other disease?

Having a pathogenic variant makes you more likely to develop disease than the general population, but it doesn’t guarantee you’ll get sick.

Sometimes, a pathogenic variant builds proteins that make small errors. Each mistake doesn’t matter much, but the consequences accumulate. If proteins that deal with cholesterol don’t work well, excess cholesterol can collect in the arteries and eventually lead to heart disease.

Proteins may also make a few big errors that are so bad they cause a disastrous chain of events. When a protein’s job is to fix problems that lead to tumors, like the protein made by BRCA1, key mistakes in the wrong places can let cancer take root.

Occasionally, the non-pathogenic variant gets damaged in one part of the body and starts producing defective proteins. The backup fails. If neither copy of a BRCA1 gene makes proteins that effectively do their job to prevent tumors, cancer can develop in that body part. 

In many cases, though, the proteins made by a pathogenic variant are good enough. They aren’t the best at their job, but they don’t make enough errors to cause disease.

About 50–80% of women who inherit one BRCA1 pathogenic variant develop breast cancer. In these women, proteins make enough mistakes to start a disastrous chain reaction that leads to disease. In the other 20–50% of women, the problems don’t get that far. Not everyone with a pathogenic variant develops its associated disease, a concept called incomplete penetrance.

Some people who don’t inherit a pathogenic variant will still get cancer. Proteins made by non-pathogenic variants, no matter how good they are at their jobs, can make mistakes or get damaged, too. Whether you have a pathogenic variant or not, your risk of disease increases with age because mistakes accumulate over time.

If you have a pathogenic variant, do you have control over whether you’ll eventually get sick?

It depends on the disease. Fortunately, you can lower your chances of developing some diseases through preventative actions.

Most people don’t find out they have a pathogenic variant until they already have the disease, when it’s too late for prevention. Learning you have a pathogenic variant before you develop a disease can be a shock, but you can use that knowledge to improve your odds of a healthy life.

With certain variants that carry a higher risk of heart disease, you can take statins to clean up some of the mistakes your proteins make.

With certain variants that carry a higher risk of cancer, you can get frequent screenings to catch a tumor early. You can remove organs to prevent the cancer starting.

Your doctor and genetic counselor can tell you the recommended prevention steps for your variant.

How can you find out whether you have a pathogenic variant before you get a disease?

Doctors and genetic counselors can order genetic testing to find variants in your DNA that are known to be pathogenic.

If a person is diagnosed with a pathogenic variant, their children have a 50% chance of sharing the same variant. Those children can benefit from testing, so they can learn about their risk of preventable disease.

Other relatives likely inherited the variant, too. Family outreach navigators at ConnectMyVariant can help you examine your family tree and identify the people most likely to benefit from testing.


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