Modern genetics is changing the way that humanity understands disease, identity, and even the definition of “health.” The scope of discovery is changing our daily lives in all sorts of ways too. New medications are hitting the market, people are learning about their ancestry, and we’re able to treat diseases that twenty years ago were unstoppable. Many of these new discoveries have been driven by the advent of improved sequencing techniques and storage capacity. Whereas research used to be driven by individual scientists, it’s now a team-based activity with a focus on ever larger patient populations. Discoveries are now happening at a rate that has surpassed any of our expectations.
A glance back in time
It’s been fourteen years since the Human Genome Project generated the first reference human genome. The project took over a decade and about three billion dollars in funding. This milestone was just a new phase of a journey of genetic exploration that actually began over a century ago with a monk named Gregor Johann Mendel.
Through his experiments with pea plants, Mendel discovered dominant and recessive genes. And although it would take many years until his work was recognized, the monastery’s five-acre garden became the breeding ground for the study of genetics.
In the past 150 years or so, much of the research around genetics has sought to answer questions around ancestry and health: how do our genes, passed onto us by our family, contribute to disease? What environmental factors are needed to trigger them, and how, if at all, can we prevent disease from happening in the first place? Where in the human genome are the genes responsible for rare diseases? Questions like these have led researchers to collect a tremendous amount of data that has gotten us to where we are today. But there’s still so much we don’t know. And as we learn more, more questions arise.
Big databases = big discoveries
Today, the landscape of genetic discovery is changing rapidly; breakthroughs that may have taken a scientist’s entire career can now happen while a grad student gets her PhD. Increased sequencing capability, computing power, and data storage, coupled with decreases in cost are allowing us to generate, process and access data like never before. These tools enable researchers to examine hypotheses more rapidly. For example, the Genome Aggregation Database (commonly known as “gnomAD”; and formerly as “ExAC”) or DiscovEHR are collections of hundreds of thousands of genomes and exomes collected from an international coalition of scientists contributing data from all over the world. Based on the volume of available data alone, repositories like DiscovEHR and gnomAD can outperform even the largest single studies.
The next frontier
Ever since Mendel, most genetic studies have focused on discovering single gene causes for traits or disease. These studies were successful in describing disease such as Huntington’s Disease, which was the first autosomal dominant genetic disease ever discovered, and the BRCA1 and BRCA2 contributions to breast and ovarian cancer. The discovery of the gene variants that led to specific diseases then helped lead to treatments, like in the case of Fabry disease. However, traits, medical conditions, or significant predispositions to a condition that are caused by a single gene were the “low hanging fruit” of genetics research.
In many cases, the genetic contributors to the majority of diseases or traits are complex and interwoven with the environment. This is one of the reasons why genetic information is often described in terms of probabilities with terms like “risk”, “odds”, or “predisposition”. For example, much like smoking increases your risk for a heart condition, a certain combination of genetic variants can also increase a person’s risk for a heart condition. However a heart condition is not a guaranteed outcome, it is just more likely with certain genetic variants.
These complex traits, where genetics and environment interact, are things like height or type 2 diabetes. For example, researchers estimate that there are hundreds or even thousands of genes that affect a person’s height, but if that person doesn’t get appropriate nutrition as a child, she is less likely to be as tall as she might have been. Now if you are trying to figure out which genes affect height, it’s going to get very tricky once you realize that nutrition plays a role, and whether or not a person gets appropriate nutrition could be due to several factors, including metabolism or the availability of nutritious food. Our ability to tease out the genetic and environmental causes of traits require the use of other data beyond DNA information. It is information like how you eat and exercise that together helps put context around genetics and helps researchers understand what factors play a major, moderate, or minor role in deciding if a person develops a trait.
Everyone can benefit
Historically, genetic research has mostly been performed on samples from European research participants. This has reduced our ability to make genetics widely applicable to minority groups. However as the racial, ethnic, and geographical diversity of sequenced DNA samples expands, so will our ability to properly diagnose and treat disease, understand ancestry, and make better decisions around wellness, for people from all over the world.
And having samples from diverse research participants is important because it’s possible that a variant that is rare in one population is not so rare in another population. This fact, along with understanding other factors in those populations, like diet and environment, can help tease out answers about the impact of having a particular genetic variant, and if that impact changes depending on your ancestral background.
The take home message is that the more diverse our resources, the better we can interpret an individual’s genetic information. An example would be that samples from individuals who have roots from Latin America could help better interpret variants from individuals whose roots are from East Asia. Large-scale research programs that actively recruit historically understudied populations, such as the National Institute of Health’s All of Us research program, will accelerate and improve our ability to discover and interpret variants.
A trajectory of discovery
Mendel landed us on the moon, but now we’re headed out of the solar system. Genetics has come a long way from simple autosomal dominant and recessive traits in pea plants. At Helix, our mission is to bring scientific breakthroughs to the world through affordable, convenient, and accurate DNA sequencing. We want to help every person live a better life through the power of personal DNA discovery. As genetics research takes the next leap forward, we’ll comb the literature to make sure we’re keeping up to offer you products based on the most up-to-date information.
To learn more about Helix, visit helix.com.