Understanding how genes, DNA, and proteins lead to inherited retinal disease

While the science of genetics might not actually be rocket science, it’s just as complex. We checked in with a genetic counselor, and asked her to explain how genes, DNA, and proteins create the “blueprint of you.”

As a genetic counselor, I spend my days talking with people about their personal and family health histories and the possibility of inherited conditions, including inherited retinal disease (IRD). While I think about cells, DNA, and inheritance daily, most of the people I talk with haven’t had to think about this stuff since high school biology! One of the most important parts of my job is to help people understand how our genes can impact our health and how genetic testing may or may not affect how healthcare providers manage a person’s care.

Before embarking on genetic testing, it is important to understand a few key points:

• What are genes?
• What are genetic changes (i.e., mutations)?
• What can genetic testing tell you?
• Why does genetic counseling matter?

I think about our genes like recipes. Each recipe gives the ingredients and instructions for a favourite meal or dish. Our genes give the ingredients and instructions for creating a protein, which performs a function in our body.”

What are genes?
Genes are the instructions that tell our bodies how to grow and develop. I think about our genes like recipes. Each recipe gives the ingredients and instructions for a favorite meal or dish. Our genes give the ingredients and instructions for creating a protein, which performs a function in our body.

Here is how it works. The DNA alphabet is made up of 4 letters: A, T, C, and G. Our genes use that alphabet to create a series of three letter words, called amino acids. A string of amino acids creates a protein, which is what performs a function in our bodies. While each of our cells contains all of our genes, each cell has a set number of genes that are active, based on what that specific cell does.

We have over 19,000 genes in each of our cells. Our genes come in pairs, one copy of each gene from mom and one copy of each gene from dad. There are over 30 genes that are specific to retinal function. Here’s a helpful video explanation of how genes, chromosomes and our DNA work together, from Science Explained.

What are genetic changes (i.e., mutations)?
We know that some traits, like the shape of our ears or the color of our hair, are decided by the genes we inherit from our parents. Every individual has many changes, or variants, in their DNA sequence. There are three different types of genetic variants:

• Pathogenic variant (i.e., mutation), or a change that stops the gene from working properly and is known to cause health concerns, such as an IRD
• Benign variant, or a change in the DNA sequence that is common in the general population and does not cause health problems
• Variant of uncertain significance (VUS), or a change in the DNA sequence that may or may not lead to health concerns. Typically, when a VUS is found, there is not enough information to say for sure that this change is normal or problematic

What can genetic testing tell you?
Genetic testing looks for changes in certain genes that may explain a person’s health concerns. For IRDs, genetic testing can be used to identify specific genes in a person known to cause an IRD. There are three possible results that can come from genetic testing: Positive, Negative, or Inconclusive.

• Positive: A positive result confirms a diagnosis and identifies the specific genetic change that caused the IRD. This can also provide information about the anticipated course of the disease. Confirming a genetic diagnosis can clarify how that condition was inherited, which can provide valuable information to determine if other family members are at risk to develop an IRD.
• Negative: A negative result means that the test did not identify a genetic change. This does not mean that a condition is not genetic. Genetic testing is not able to identify every single change in our DNA. There may be a pathogenic variant but it was not detected by the test. Most genetic tests only look at a select number of genes, so a negative result may mean there is a change in a gene that was not analyzed by the test performed. There may be more options for testing in the future.
• Inconclusive: An inconclusive result means a VUS was identified. Identifying a VUS does not confirm or rule out a diagnosis of IRD. It also can’t provide information on the specific diagnosis or risk for family members. Often over time a VUS can be reclassified to either benign or pathogenic, but this can take years. If an inconclusive result is found, other testing may be considered.

Why does genetic counseling matter?
Genetic counseling is an important part of any genetic test. A genetic counselor can help to interpret what genetic testing results mean in the context of an individual’s personal and family history. With training in both medical genetics and counseling, a genetic counselor can also help individuals and families adjust to this information and provide support. Regardless if a genetic test is positive, negative, or inconclusive, a genetic counselor can work with you and your other healthcare providers to make a plan for your care.

Jennifer Schwab, M.S., C.G.C.

Jennifer Schwab, MS, CGC, a board-certified genetic counselor, received a B.S. in Biology from Northeastern University in 2010 and an M.S. in Genetic Counseling from the Boston University School of Medicine in 2012. She is a Clinical Genetic Counselor at Rhode Island Hospital and a Teaching Associate at the Warren Alpert Medical School of Brown University. Jennifer serves as a member of the New England Region Genetics Group Board of Directors, and active in the National Society of Genetic Counselors.