Jessica Dawson HDSA Researcher Spotlight: Jessica Dawson
Written by: Dr. Tam Maiuri
Edited by: Dr. Kaitlyn Deschamps
Why tiny changes in DNA can make a big difference in Huntington’s disease
Huntington’s disease (HD) does not look the same for everyone. Even people with the same genetic diagnosis can experience symptoms that begin at different ages, progress at different speeds, and follow different paths. For Jessica Dawson, these gaps between what genetics predicts and what people actually experience are what drew her into the field.
When the Science Became Personal
Like many researchers in the HD field, Jessica came to science through a love of genetics but stayed because of the people. She trained in South Africa, where she was first captivated by how small changes in DNA can confirm, challenge, or complicate what we think we know about the disease. Over time, though, it became clear to her that genetics alone rarely tells the whole story.
During her training, she encountered Huntington’s disease in lectures and coursework, but it was her time in HD clinics that left a lasting impression. Meeting individuals and families living with HD shifted her perspective. The DNA sequences she studied were no longer abstract; they belonged to real people trying to understand what the future might hold.
Her work also included a rare condition that closely resembles HD, called Huntington disease–like 2 (HDL2), which is caused by a different genetic mutation and occurs more often in people of African ancestry. Studying both conditions deepened her awareness of how much diversity exists within diseases that are often described too simply.
Those experiences shaped the direction of her research. Jessica became interested not just in what causes HD, but in why the disease can look so different from one person to the next, and how small variations in DNA can have outsized effects on when and how HD unfolds.
When One Number Isn’t Enough
Huntington’s disease is caused by an expanded stretch of DNA made up of repeated CAG letters in the HTT gene. For decades, the length of those repeats has been used to estimate when symptoms might begin. While useful on average, that number does not reliably predict how HD will unfold for any one person.
Jessica’s work focuses on what lies within those repeats. Within the CAG sequence, short CAA segments normally appear at regular intervals, acting like small breaks in the repeating code. She studies rare variants in which these interruptions are missing, creating a longer, uninterrupted stretch of CAGs that is associated with earlier symptom onset. Loss of these CAA interruptions is not always detected by standard genetic testing, but growing evidence suggests they can meaningfully influence how the disease unfolds.
Before Jessica’s project, the loss of CAA interruption was already known to shift the age of onset. What remained unclear was how large that effect was, whether it influenced disease progression, and what biological mechanisms might explain it.
What They Found, and What They Didn’t
Jessica’s analyses showed that loss of CAA interruption has a clear and substantial impact on Huntington’s disease. People who carry uninterrupted CAG repeats tend to develop symptoms significantly earlier than expected, by more than a decade on average, when based on repeat length alone. This effect is larger than any other known genetic modifier. Her work also showed that these variants are associated with faster disease progression, indicating that they influence not only when HD begins, but how it unfolds over time.
Her study also tested leading ideas about why this happens. One hypothesis has been that uninterrupted repeats accelerate disease by increasing somatic instability, meaning the CAG stretch continues to expand in certain cells over time. Another possibility was that the variants exert their effects through repeat-associated non-ATG (RAN) translation, producing additional toxic protein products. When Jessica examined bulk brain tissue, however, neither mechanism fully explained the strong clinical effects she observed.
Rather than closing the door on these processes, her findings highlight the limits of what bulk tissue can reveal. Many cell populations analyzed together like this can hide any disease-driving changes that may occur within specific, vulnerable cell types. By showing both what does and does not explain the impact of lost CAA interruption, Jessica’s work defines the size of the effect while sharpening the field’s focus on the biological questions that matter most.
Why This Matters for Families Right Now
For families, the most immediate impact of this work lies in how genetic test results are interpreted. Today, CAG repeat length is often treated as a single, fixed number. Jessica’s findings show that this approach can miss important details. For people who carry uninterrupted CAG repeats, symptom onset may occur much earlier than expected, even when reported repeat lengths appear similar.
This is especially important when the repeat falls within the 36-39 range, where a person may or may not develop symptoms within a typical lifetime, also known as reduced penetrance. In this range, overlooking sequence interruptions can lead to underestimating risk or misjudging timing, sometimes by many years. For individuals and families, that uncertainty can affect life planning in profound ways, from work and finances to caregiving expectations and personal decisions about the future.
Jessica emphasizes that this work is not about changing diagnoses overnight. Translating genetic insights into clinical practice takes time, validation, and consensus. But by demonstrating the size and consistency of this effect, her research strengthens the case for updating how genetic testing is interpreted and reported.
What Progress Looks Like from the Inside
Jessica describes HD research as a balance between urgency and patience. She is acutely aware of how slow progress can feel for families, while also stressing the importance of doing the work carefully and collaboratively. In her view, the strength of the HD field lies in its openness, with researchers building on one another’s findings rather than working in isolation.
Success, for her, is not novelty but usefulness. The best outcome would be for insights like these to become routine parts of genetic testing and counseling, helping families navigate HD with fewer surprises and more clarity.
Where Care and Curiosity Meet
For Jessica, the most meaningful part of her work has always been the people behind the data. Meeting individuals and families affected by HD changed how she thinks about genetics, not as an abstract code but as information that carries real responsibility.
That responsibility shapes how she approaches her research. She is careful with interpretation, attentive to detail, and cautious about drawing conclusions before the evidence is ready. For Jessica, progress in HD research is not about speed. It is about precision, honesty, and taking the time to get things right, because the consequences matter.
Fast Facts
Researcher: Jessica Dawson
Institution: The University of British Columbia
HDSA Program: Human Biology Project
Research Focus: Genetic modifiers of Huntington’s disease onset and progression
Approach: Analysis of rare sequence variants within the HTT CAG repeat, including loss of CAA interruption
Why It Matters: These variants can substantially accelerate disease onset and progression, with direct implications for genetic testing and counseling.
