For people like me working in the biological science sector, the annual DNA Day (every April 25th) is always a cause to raise a toast, but this year was special. It marked the 70th anniversary of the discovery of the double helix by Watson and Crick (and Franklin) and the 20th anniversary of the completion of the Human Genome Project.
That project began in 1990, led by the US National Institutes of Health (NIH) with an international consortium that included Health Canada. But its actual completion date is a bit murky. President Bill Clinton and NIH leaders announced a draft in 2000, but didn’t declare the project completed until April 2003. Even then, it identified only 92 per cent of our genes. Not until 17 years later, in May of 2021, did we get publication of the remaining eight per cent, or I should really say almost all of the remaining genes. Even that version missed 0.3 per cent of the nucleic acid bases that make up our DNA. A team finally published the gapless genome about a year ago.
There is just one big problem with this gapless genome. It doesn’t represent the diversity of humankind. While we all share 99.9 per cent of all genes, that remaining 0.1 per cent accounts for a heck of a lot of genetic variation considering we have more than three billion nucleic acid base pairs.
NIH recognized this gap in 2015 and launched the All of Us Research Program with the goal of collecting and sequencing DNA from one million people, representing the full diversity of our population. But more important is to also collect current and on-going information about health status and changes in health. Those data can, in turn, make any genetic variants that researchers find actionable. For example, if teams find that certain lifestyles can minimize the risk associated with a genetic variant, people can be advised on how to mitigate the risk and perhaps show that genes aren’t fate.
Canada launched a project with similar goals in 2007. Dubbed the Personal Genome Project Canada, its website suggests the public has a vital role to play if we are to make personal genomics useful. It states:
“We are recruiting volunteers who are willing to share their genome sequence and many types of personal information with the research community and the general public, so that together we will be better able to advance our understanding of genetic and environmental contributions to human health and disease.”
The All of Us project grew out of a precision medicine working group advising the director of the NIH. It set out goals for what became “All of Us,” stating that precision medicine is:
- Based on you as an individual;
- Takes into account your environment (where you live), lifestyle (what you do), and your family health history and genetic makeup;
- Gives health care providers the information they need to make customized recommendations for people of different backgrounds, ages, and regions;
- Helps you get better information about how to be healthier;
- Reduces health care costs by matching the right person with the right treatment the first time.
The NIH released the data set for the first 100,000 whole genome sequences a year ago and released data on another nearly 150,000 last week. The consortium of institutions working on All of Us stores the anonymized data in the cloud where they are available through the All of Us Researcher Workbench available to research teams around the world. In addition to information from volunteers’ electronic health records, FitBit or other wearables and survey answers, it also has links to the Census Bureau’s American Community Survey to provide another dimension on the interaction of genetics and environment.
Unlike most genetic studies to date, which have populations that average 90 per cent white European descent, 50 per cent of the information in the initial All of Us data come from individuals who identify with racial or ethnic groups that have historically been underrepresented in research. The project began enrolling individuals in 2018 and will follow each person for 10 years.
Another novel value of All of Us comes from the fact that it is sequencing the whole genome, not just the small portion in genes that code for the proteins that make us. Those so-called “non-coding” sequences often have a major role to play in how genes get expressed—when they get turned on and off—and can have a significant role in determining how genetic variations impact a person’s health.
The Canadian project released its first data set the year NIH started collecting data in 2018. The Personal Genome Project Canada published that 53 of 56 people in the initial cohort had at least one disease-associated genetic variant. When they looked at those genetic differences, just 24 per cent had obvious health implications. However, another major finding of studies like these is not genes that increase risk of disease, but genes that impact how people react to medication. All 56 individuals had either a disease risk or a medication risk.
Taken together, these new era genomic projects should provide a much more complete view of us. Yes, all of us. Given the fact that I routinely get Facebook consumer ads offering whole genome sequencing, it is past time the entire research community catches up with how relatively easy it has become to include a genetic component in studies. And then to look at ways to make those studies more inclusive.
The NIH’s National Human Genome Research Institute, home to the All of Us project, posted a tweet late last month of the grumpy cat with the caption:
“Us not taking your research seriously until your study is inclusive and represents all of human genetic diversity.”
(Click here to view the tweet on Twitter.)
Don Gibbons
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