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Have you ever stopped to think about the process your doctor uses to diagnose an illness or disease? When a patient comes into the office with symptoms, doctors often become detectives. While some diagnoses are obvious, there are symptoms that can result from many different conditions, such as fatigue or joint pain.

If you experience symptoms that could occur with different health conditions, doctors typically make a differential diagnosis. They talk to you about your health history, examine you, and make a list of conditions that could cause your symptoms. They may perform tests, such as blood tests or imaging tests, to rule out certain conditions.

Today, advancements in the study of genetics have given doctors new tools to discover what’s behind a person’s symptoms. These tools can also help determine your future risk of disease. Known as next-generation sequencing, or next-gen sequencing, these techniques are changing how doctors treat conditions caused by changes in genes (mutations).

What Role Do Genes Play in Your Health?

Think of genes as little bricks that contain pieces of code called DNA. DNA tells your body how to make molecules and proteins. Your body then uses these molecules and proteins to perform different jobs that keep you alive and help you function.

Your genome is all the genes in your body. By learning more about your genome and any genetic mutations you have, doctors can diagnose certain health conditions and determine how to treat you. This information can also help you understand your risk for developing disease.

How Do Gene Changes Happen?

You can inherit genetic mutations from one or both of your parents. But some gene mutations happen on their own (spontaneously).

Some genetic mutations occur more often in certain families or communities. Lina Ghaloul-Gonzalez, MD, a geneticist at UPMC Children’s Hospital of Pittsburgh, studies genetic mutations using next-gen sequencing. Her work has examined genetic disorders that run in Amish and Mennonite communities in Western Pennsylvania.

What Types of Genetic Testing Do Doctors Use?

Your doctor will consider several factors when deciding what type of genetic testing to use. You may have:

• Single gene testing. These tests look for changes in one gene. Your doctor may recommend single gene testing if you have specific symptoms or a family history of a genetic disorder.
• Gene panel testing. These tests focus on changes to groups of genes associated with certain symptoms or higher risk of developing diseases.
• Next-gen sequencing. These tests focus on many genes. Your doctor may recommend next-gen sequencing if you have many symptoms of unknown origin or several complex health conditions.

What Is Next-Gen Sequencing?

To learn about gene mutations in an individual, researchers study the order (or sequence) of DNA in their genes. Gene sequencing helps doctors know which genes have mutations and what those mutations are.

Sequencing DNA used to be a time-consuming process that could take many months or even years. Next-gen sequencing now uses automation and technology to study a large amount of genetic material in just a few months. Next-gen sequencing methods include:

Whole exome sequencing

In whole exome sequencing, researchers study specific pieces of material within DNA, known as exons. Exons tell genes how to make the proteins your body needs. Studying the order of all your exons (your exome) helps researchers identify changes in how genes tell your body to make proteins.

Gene mutations in the exon are most often responsible for causing genetic disorders. Researchers use whole exome sequencing to try to find mutations that are causing health conditions or diseases. They also use this method to identify mutations that could cause health problems in the future.

Whole genome sequencing

In whole genome sequencing, researchers examine changes in any part of the gene in all the genes in your body (your genome). They may use it to identify mutations in structural parts of genes that aren’t involved in producing proteins, known as noncoding variants. A noncoding variant is a change to the DNA structure of a gene.

How Do Genes Contribute to Disease?

Changes or damage to genes can cause a range of conditions and diseases. Genetic disorders include:

• Single gene disorders. These disorders occur due to a mutation in one gene. For example, Fragile X syndrome results when a mutation to one gene prevents the production of a protein that affects brain development.
• Chromosomal disorders. These disorders occur when a chromosome (the structure that contains the genes) has a mutation. For example, Down syndrome occurs in people born with an extra chromosome.
• Complex diseases. These occur when mutations in more than one gene, plus environmental factors, cause a disease. For example, type 1 diabetes may result from changes to various genes.

Some gene mutations make you more likely to develop a disease or health condition. If you have the genetic mutation that causes the condition, you’re at higher risk. But that doesn’t always mean you will develop the condition.

Which Genetic Mutations Cause Disease?

Some genetic changes and their links to disease are well known, including:

• BRCA gene mutations and breast cancer.
• Sickle cell anemia.
• Phenylketonuria (PKU).

Researchers continue to study genetic mutations to learn about their role in disease. With next-gen sequencing, researchers can do whole exome sequencing and whole genome sequencing and get results faster.

How Can Next-Gen Sequencing Help Doctors Treat Me or My Child?

“Next-gen sequencing helps doctors connect the dots to determine what’s causing different symptoms they see in a patient”, says Dr. Ghaloul-Gonzalez. Doctors use genetic test results to develop personalized treatments for babies, children, teens, and adults with rare disorders.

What Is the Future of Next-gen Sequencing?

Dr. Ghaloul-Gonzalez notes that next-gen sequencing is an important tool for discovery. But functional and laboratory studies still play a critical role in diagnosing disease and determining risk. As next-gen sequencing evolves and becomes routine, it may help provide a more complete picture of a person’s health and disease risk.

Editor's Note: This article was originally published on January 26, 2023, and was last reviewed on August 29, 2023.