Many of the disciplines within academia — mathematics, biology and chemistry — have been studied for thousands of years by many different cultures and civilizations. But only for 160 years has genetics been formally studied as its own discipline stemming from Mendel’s “Experiments on Plant Hybridization” in 1865.
During this short time, our understanding of genetics has accelerated at unprecedented rates, allowing breakthroughs in medicine, biology and many other fields. One of these breakthroughs has been determining genetics as the cause of many inherited disorders that have been present throughout human history.
In 1872, newly graduated Dr. George Huntington wrote and published his paper “On Chorea,” which contributed a clinical description of a disease that now bears his name, Huntington's disease (HD).
Affecting around three to seven out of every 100,000 people, it is a rare but present genetic condition that affects many, with an average onset of symptoms occurring at 35 to 45 years old. Scientists have been studying the causes of the disease since its discovery, but new research suggests it may be different than previously thought.
Huntington’s disease is neurodegenerative, meaning the cognitive and motor functions of the patients will decrease as the condition progresses. This can cause a multitude of problems, such as difficulty speaking and loss of fine motor function in the early stages. Later on, there is a loss of muscle control and spasms, along with a stark decrease in psychological functioning.
Our understanding of Huntington's disease currently focuses on a series of repeated segments of the amino acids (the building blocks of DNA) CAG: cytosine, adenine and guanine. Persons with 36 to 39 CAG repeats may or may not develop the disorder, and those who have 40 or more CAG repeats will most likely develop HD. The more repeats over 40, the earlier in life Huntington's develops.
This means the more CAG repeats a person has in the specific Huntingtin gene, the more likely they will develop Huntington’s disease earlier and more intensely.
The theory is that the repeats cause cumulative cell damage within the brain that becomes substantial enough to cause symptoms decades into the patient's life.
While this principle has held through the present, it doesn’t give the complete picture behind the scenes. A new preprint authored by Robert Hansaker, recently released on May 20 from the Broad Institute of MIT and Harvard found the number of repeats not to be the cause of HD and disputed the idea of cumulative cell damage.
Looking at the Huntingtin gene, this preprint discovered that the number of CAG repeats increases over time, where having more than 150 repeats causes the onset of symptoms and cell damage associated with HD.
This tells us something interesting: instead of the problem being the amount of CAG repeats someone inherited, the problem is that the DNA replication mechanism is malfunctioning. This malfunction creates additional repeats over many years. Once you reach the threshold, there is acute degradation within the cells, which causes motor function and cognitive decline.
Does this really change anything? The short answer is yes.
The preprint noted that there is a possibility for intervention to slow down and postpone HD symptom onset. This could be done using therapies that target the mechanisms responsible for the increase in CAG repeats.
This research not only advances our understanding of Huntington’s disease but also opens the door to future studies looking into genetic disorders we think we understand but ultimately don’t. As many genetic diseases are linked to specific genes of interest, changing the scope to look at the mechanisms of these diseases as the driving factor of adverse outcomes can help research and medicine become more comprehensive and effective.
