April 27, 2020 (Huntsville, Ala.) – Neurodegenerative diseases such as Alzheimer disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia can be devastating for patients and families, particularly in cases when symptoms show up in people younger than 65.
More than 5 million Americans are currently living with Alzheimer disease. Another 20,000-30,000 people have frontotemporal dementia and at least 16,000 have ALS. While scientists have some ideas about what causes these conditions, there’s a lot of information they don’t have, particularly about how a person’s genome — the suite of genetic material or DNA that they’re born with — might affect disease onset.
Now, scientists at the HudsonAlpha Institute for Biotechnology, the University of California, San Francisco (UCSF), and the University of Alabama at Birmingham (UAB) have uncovered a gene that doubles the risk of becoming ill with one of these diseases.
“This work would have been impossible without the grassroots support of donors,” said Richard M. Myers, PhD, HudsonAlpha president and science director. “Being able to do projects like this that address the underlying causes of multiple different neurodegenerative diseases could make a real difference in finding earlier diagnostics and new treatments.”
The researchers gathered DNA samples from more than 1,100 people in an effort led by Jennifer Yokoyama, PhD, an assistant professor of neurology at the University of California, San Francisco. About half of these people were healthy, while the other half had Alzheimer disease, ALS, or frontotemporal dementia. Then the scientists used a technique called whole-genome sequencing to learn what each individual’s genetic code looks like.
With more than one thousand genetic codes in hand, the researchers used computer programs to comb through the sequences and find genetic variants, or things that were different. They determined that people with neurodegenerative diseases were more likely to have variants in a gene named TET2. They discovered this gene after analyzing both the parts of the genome that serve as a blueprint for making proteins, the molecules that do things in the body’s cells, and the parts of the genome that control when and where those proteins get made.
Then, the research team looked at DNA sequences from more than 32,000 healthy people and people with neurodegenerative diseases. They confirmed that the variants they saw in the first 1,100 genomes they looked at were also present in other people with Alzheimer disease, ALS, and frontotemporal dementia more often than in healthy people.
“We’re excited that we did find a new genetic association here,” said Nicholas Cochran, PhD, a senior scientist in the Myers Lab at HudsonAlpha.
You never know what genes might show up in a research project like this, but TET2 is exciting. This gene is the DNA blueprint for a protein called TET2, which has already been shown to have a role in maintaining the brain’s DNA. The researchers think the variants that they found that lead to a non-functional version of the protein might disrupt how the brain ages and contribute to the development of Alzheimer disease, ALS, and frontotemporal dementia.
In addition to the generous support of local Huntsville donors to the HudsonAlpha Foundation Memory and Mobility Program, the work, which was recently published in The American Journal of Human Genetics, was funded by the Rainwater Charitable Foundation, the Daniel Foundation of Alabama, the Larry L. Hillblom Foundation, and the National Institutes of Health National Institute on Aging.
About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to developing and applying scientific advances to health, agriculture, learning, and commercialization. Opened in 2008, HudsonAlpha’s vision is to leverage the synergy between discovery, education, medicine, and economic development in genomic sciences to improve the human condition around the globe. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education and includes more than 30 diverse biotech companies on campus. To learn more about HudsonAlpha, visit hudsonalpha.org.