DNA and Huntington's Disease
DNA discovery has allowed researchers to identify the genetic basis for many diseases. In doing so, the path has been paved for new treatments and enhanced knowledge for preventing disease. In the case of Huntington's disease, DNA plays an important role in our understanding of how the disease occurs and hopefully one day, how it can successfully be treated.
What is Huntington's Disease?Huntington's disease is a genetic disease that affects the central nervous system. It is unusual in comparison with many other disorders in that the symptoms typically show in adults aged 30 to 40 years, although they can be evident earlier or later than this age range. Symptoms generally include involuntary movements and a loss of motor control. A person with Huntington's disease may also suffer from personality changes, memory loss and a compromised mental capacity.
DNA and its Relationship to Huntington's DiseaseHuntington's disease is an autosomal dominant disorder, which means that the gene is an autosomal chromosome as opposed to one of the sex chromosomes. If you think about the human body, we each have forty-six chromosomes that come in pairs - one from each parent. The first twenty-two pairs are autosomal chromosomes and the twenty-third pair consists of sex chromosomes. Since Huntington's disease is autosomal dominant, it means that the gene implicated in the disease is on one of the autosomal chromosomes rather than the sex chromosomes. It has been found that the fourth autosomal chromosome is involved in the disease. Those who are affected have one gene in the gene pair that is not functioning properly, which then causes it to express itself to a greater degree and thus dominates the properly functioning gene.
Those who are familiar with the basics of DNA will recall that a chromosome contains DNA, which then contains genes. Within the structure of DNA, there are nucleotides composed of a sugar, phosphate and base. In Huntington's disease, there is a DNA sequence of CAG that can be duplicated many times over, in what is known as a trinucleotide repeat. The CAG refers to the DNA bases cytosine, adenine and guanine. While the general population might have the CAG duplicated up to twenty-six times, those with Huntington's disease have it repeated from forty to more than a hundred times.
Recent Research into DNA and Huntington's DiseaseOne of the questions that researchers have regarding Huntington's disease involves its late onset in life. A recent theory is that the CAG segment expands over time in cells that do not divide, such as nerve cells. Thus, the disease then progresses as time passes and symptoms present themselves when a person is in his or her 30s or 40s - perhaps a bit earlier or later.
For those of us without Huntington's disease, we are normally susceptible to oxidative lesions, which are by-products of inhaled oxygen but we have DNA repair enzymes that work to keep these oxidative lesions in check. In a person with Huntington's disease, the body's cells try to remove the oxidative lesions, which are thought to cause the CAG segment to expand. DNA repair enzymes still exist in those with Huntington's disease as with the general population, but these repair systems can become overwhelmed by the oxidative lesions as time goes on. It is likely that this expansion of the CAG segment and reduced capacity of the DNA repair system to handle oxidative lesions leads to the late onset of symptoms. The link between oxidative lesions and Huntington's disease has been confirmed with laboratory experiments on mice. Scientists are hopeful that new treatments that address these oxidative legions can prevent the onset of the disease. They are also optimistic that the research might be helpful for other diseases where oxidative lesions are thought to play a role, such as Alzheimer's disease.