Next Generation Sequencing Can Detect Disease, Help Manage Risks and Track Infectious Diseases

Next Generation Sequencing Can Detect Disease, Help Manage Risks and Track Infectious Diseases

Inside each of the cells in your body is a blueprint, a set of 23 coiled pieces of DNA. This DNA tells your cells when to grow and divide, what color your hair will be, or even which diseases you might be most vulnerable to. Your complete set of DNA is called your genome.

Until recent years, it was difficult and expensive to sequence (aka ‘decode’) a human genome. The first effort to sequence the human genome took over a decade, and cost $2.7 billion dollars. Today, an entire human genome can be sequenced in about 24 hours for less than one thousand dollars. This is possible because of next generation sequencing.

What is Next Generation Sequencing?

Next generation sequencing (NGS) is a catch-all term for methods of DNA sequencing that are much faster and more cost effective than previous technologies. Usually it involves chopping up DNA into smaller fragments, and then making copies of the fragments you want to study. These fragments are then fed into an NGS machine, which reads each fragment at the same time, then puts them back together in the proper order.

Cost Per Genome - August 2019 - next generation sequencing
In recent years the cost of human genome sequencing has decreased significantly. Image courtesy of The National Human Genome Research Institute.

Next generation sequencing can detect diseases earlier.

Dr. Greg Hawkins, a professor of biochemistry at Wake Forest, has over 30 years of experience in DNA sequencing and is currently a member of the Wake Forest School of Medicine Center for Precision Medicine. He is particularly enthusiastic about the possibility of using NGS to detect rare genetic diseases early in life.

“For example,” explains Dr. Hawkins, “today when a baby is born, we take a blood sample from their heel and test for metabolites that could be an indication of a genetic disease. In the old days all we could do was look for defects in proteins and changes in metabolites, we couldn’t look at the DNA to know what had caused those defects. Now we can look at the entire genome and identify a single mutation that may cause these genetic diseases in newborns.” Why is that important? Because early detection can save lives. Some conditions are easy to treat if caught early, but can be fatal if undiscovered.

Next generation sequencing can help people manage their risks of developing certain conditions.

NGS can also help people make more informed decisions about their health, and the health of their families. Dr. Hawkins shared that, after doctors discovered a blood clot in his leg, they decided to run some genetic tests and found that he had a mutation that predisposed him to these clots. “I have three daughters,” says Hawkins, “We found out that two of my daughters have this mutation as well, which also puts them at a higher risk for pregnancy complications. That’s something I wish we knew a long time ago.”

This is one potential benefit of knowing the secrets of your genome. If you know you have a high risk of developing a condition, you can change your behavior accordingly. However, some worry that genetic information could be used against them.

The availability of personal genetic information raises concerns about privacy and discrimination.

There are laws that prevent employers from discriminating against employees based on their genetics, but “what if insurance companies got a hold of a newborn’s genome sequence, and discovered they had a high genetic disposition for increased disease risk? They might jack up the insurance premiums. They can already do that for preexisting conditions,” notes Dr. Hawkins. “But does genetics really count as a preexisting condition? In some cases, a genetic mutation might mean you will definitely develop a certain condition, but not always. Sometimes it just affects your risk.”

NGS also helps identify which microorganisms live in your body, and how that affects your health.

Researchers are also using NGS to understand the makeup of the microbiome – the different colonies of microorganisms like bacteria that live on and in your body. Using NGS to study microbiomes could help doctors diagnose infectious diseases, or better manage complex conditions like obesity or Type 2 diabetes.

NGS helps researchers study and track infectious diseases like COVID-19.

Because NGS can be used to sequence the genome organisms like bacteria and viruses it is an important tool for public health officials to track the spread of diseases. The speed of NGS is invaluable when working to combat epidemics, where fast action is needed to contain outbreaks.  

NGS can even detect COVID-19. In June 2020, when this new test was approved, FDA Commissioner Dr. Stephen Hahn remarked that “Having a next generation sequencing diagnostic tool available will continue to expand our testing capabilities. Additionally, genetic sequencing information will help us monitor if and how the virus mutates, which will be crucial to our efforts to continue to learn and fight this virus.”

High cost and massive datasets are barriers to NGS adoption.

So why isn’t everyone using NGS all the time? Two reasons – cost and data management.

Although the cost of genome sequencing has decreased dramatically in the last decade, it’s still not cheap. Sequencing a human genome for research purposes could set you back hundreds of dollars. If you are doing a population study with thousands of genomes, that can add up quickly.

Additionally, sequencing a genome for clinical use is even more expensive than sequencing a genome for research. That’s because clinical sequencing tests must pass rigorous regulatory standards.

Finally, the sheer quantity of data generated by sequencing a human genome can be overwhelming. Dr. Hawkins explains “a major issue is that NGS generates massive amounts of data. You need a lot of computing power, a lot of machines to process all that data. We’re now uploading a lot of that data onto the cloud to use cloud-based processing but uploading large data sets is a slow process. That also makes it difficult for us to share data with other institutions.”

Despite the hurdles, NGS is an incredible technology that could allow North Carolinians an unprecedented level of insight into their own genetic makeup. To learn about other technologies coming out of North Carolina, check out our review of recent health and biotech projects.