Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford

Studying Huntington’s Disease

This chapter explains some of the many different types of research that scientists use to study Huntington’s Disease.

Fig Y-1: Transgenic Mouse Paw

The above figure shows a rather strange mouse paw photographed under fluorescent light. Why on earth is this paw green? Despite its appearance, the mouse is not an alien nor has it taken a bath in nuclear waste. Instead—and this also sounds crazy, but it’s true—the greenness comes from a special “fluorescence gene” that belongs to a jellyfish! When the mouse was just an embryo, scientists inserted this special gene into it and the gene became incorporated into the mouse’s DNA. When the gene then had its effects in the mouse, the resulting fluorescent protein caused the mouse’s whole body to light up, just as if it were still in the jellyfish.


You might be asking yourself: what could this green mouse possibly have to do with Huntington’s Disease (HD)? Although it is not clear from the picture, the mouse may actually have a lot to do with HD. Since a foreign gene is incorporated in its DNA, the green mouse is called a transgenic mouse. The fluorescence gene is just one example of a multitude of genes from many different animals that researchers are now adding into mouse DNA. One particular gene of interest is the human HD gene, which has been inserted into transgenic mice for research purposes for a number of years. These mice are part of the large field of animal research, a field that is teaching scientists important new things about HD.

Animal research is just one piece of the immense HD research puzzle. Other forms of HD research include family tree studies, epidemiological studies, genetic studies, postmortem studies, and clinical studies. Each of these areas of research has contributed a great deal to our current understanding of HD. More importantly, each of these areas will help contribute to the exciting breakthroughs in future HD research. These various areas of research, and some of the facts that they have already uncovered, are the subject of this chapter.

Animal Research^

  • Click here to learn about the basics of HD mouse models
  • Click here to view an article on the ethics of HD testing

Epidemiological Studies^

Epidemiology is the study of the spread of diseases within and between human populations. Similar to family tree studies, epidemiological studies involve finding which individuals show the symptoms of a disease and which do not. However, epidemiological studies differ from family tree studies in that epidemiologists generally study a greater number of people at one time. In fact, many epidemiological studies deal with the populations of entire countries, or even continents. In the case of HD epidemiology, researchers might, for example, dig through a country’s health statistics and find out how many individuals have been diagnosed with HD. These data can then be combined with other records—or perhaps with personal interviews if the individuals are willing—in order to reveal aggregate trends about HD in populations. For instance, one epidemiological study showed that five people per million get HD in Finland, as opposed to between 30 and 70 people per million in most other Western countries. Another study showed that the prevalence of HD among African Americans in South Carolina is only 9.7 per million, a strikingly low prevalence, and five times lower than the prevalence for Caucasians in the same area. These are just a few examples of the interesting findings of HD epidemiology. Since they tell us information about HD in populations throughout the world, epidemiological studies will be a vital piece in the HD research puzzle for many years to come.

Genetic Studies^

Fig Y-2: The Human Genome

Genetic studies seek to find a link between a particular gene (or genes) and a certain disease. If a genetic basis has already been established for a given disease, the studies seek to find the location of the gene(s) within the DNA. To do this research, geneticists depend heavily on data from family tree studies. They look at patterns of disease inheritance across generations of a given family, and, if possible, they supplement these data by studying the blood samples from living members. With regard to HD research, the most important question since HD was shown to have a genetic basis has been this: On which of the 23 human chromosomes is the Huntington gene located? (The 23 human chromosomes are shown in Figure Y-2). The most effective research to date to determine the location of the Huntington gene involves so-called “linkage studies”, as described below.

Linkage Studies^

Linkage studies use data from very large families with a history of HD. The principle behind linkage studies is that if nearly every person with HD in a single family shares the same version of a particular “marker trait,” such as the same color eyes or the same blood type, then the genes that code for that marker trait must be located close to the Huntington gene on the same chromosome. The marker’s gene and the Huntington gene are then said to be “linked” to one another. The logic behind such studies is straightforward—genes that lie close together on the same chromosome will tend to be inherited together over the generations. (Genes lying farther apart on the same chromosome are often not inherited together due to a complex process called recombination.)

In reality, eye color and blood type were not themselves useful as markers in HD studies, for their genes lie on chromosomes different from that of the Huntington gene. However, other markers were a tremendous help in locating the Huntington gene, including markers in a region of the Huntington-bearing chromosome called the “non-coding region.” The DNA in these regions does not code for proteins, but it still consists of a linear sequence of the chemical components called nucleotides. Using laboratory techniques, researchers found a few regions or “loci” of this DNA where family members with HD all had the very same nucleotide sequence. Since the researchers knew the locations of these particular loci, they were able to determine that the Huntington gene lies close by on the same chromosome. For example, a locus called “D4S90″ had the same nucleotide sequence in every person with HD in a particular family. Since D4S90 was known to reside on chromosome #4, researchers concluded that the Huntington gene must lie along chromosome #4, very near D4S90. Data from other loci have confirmed this fact.

Once the location of the Huntington gene was identified through linkage studies, further genetic research (including linkage studies and other types of genetic investigation) revealed more details about the Huntington gene. With the cutting-edge technologies available today, it is likely that genetic research will continue to tell us a great deal about HD.

Human Postmortem Studies^

Human postmortem studies are carried out using the donated bodies of people who have died. In the case of HD, postmortem studies have been very important in locating the specific parts of the brain that HD affects. In comparing postmortem HD brains with non-HD brains, doctors have found that HD brains often show damage or decay in the basal ganglia, whereas no damage or decay is seen in the non-HD brains. (For more information about the basal ganglia and the affects of HD on the brain, click here). Postmortem studies also offer insight into some of the cellular events that take place in the brains of people with HD. For instance, by using very special staining techniques, postmortem studies have investigated the presence of nuclear inclusions (NIs) (For more information about NIs and huntingtin protein aggregation, click here). Understanding NIs and other cellular phenomena will be tremendously helpful in developing future treatments for HD. For this reason, postmortem studies are a very important type of HD research.

Family Tree Studies^

Family tree studies (also known as “pedigree studies”) have been a tremendously successful form of HD research throughout the years. This type of research involves looking at a large number of related individuals through several generations and searching for any disease-related similarities between them. Such research, combined with blood samples taken from living family members, allowed scientists to establish that HD is a genetic disease in the first place. For more information about the most famous family tree study on HD (conducted in the vicinity of Lake Maracaibo, Venezuela), click here.

Clinical Studies^

Clinical studies (also called clinical trials) are studies that involve human subjects with informed consent. In the case of HD, these studies have been critical in identifying the various symptoms that doctors now use to diagnose the disease (For more information on symptoms of HD, click here). In fact, the very name “Huntington’s Disease” comes from Doctor George Huntington, who was the first to notice that many of his patients’ symptoms were part of the same disease.

Now that the symptoms and typical age of onset of HD are clearly defined, clinical studies today are more geared toward judging the effectiveness of particular drug treatments. After a new drug passes the test in animal studies, the U.S. Food and Drug Administration requires that clinical studies be performed to ensure that the drug is safe for humans. Once approved by the Food and Drug Administration, drugs may be sold either as prescription drugs or over-the-counter drugs.

For more information on clinical trials, click here.

For further reading^

  1. Freeman, T. B.; Cicchetti, F.; Hauser, R. A.; Deacon, T. W.; Li, X.-J.; Hersch, S. M.; Nauert, G. M.; Sanberg, P. R.; Kordower, J. H.; Saporta, S.; Isacson, O. : Transplanted fetal striatum in Huntington’s disease: phenotypic development and lack of pathology. Proc. Nat. Acad. Sci. 97: 13877-13882, 2000.
    A technical paper regarding the transplantation of fetal neurons.
  2. Robbins, C.; Theilmann, J.; Youngman, S.; Haines, J.; Altherr, M. J.; Harper, P. S.; Payne, C.; Junker, A.; Wasmuth, J.; Hayden, M. R. : Evidence from family studies that the gene causing Huntington disease is telomeric to D4S95 and D4S90. Am. J. Hum. Genet. 44: 422-425, 1989.
    A technical paper regarding a particular linkage study that showed the Huntington gene to be located on chromosome 4.
  3. Mouse paw picture obtained from National Geographic web site (

Updated by T. Wang, November 2010