MODULE 9                                                                      Huntington’s Disease

The field of bioinformatics allows biologists to use technology to answer some of their questions.  The Human Genome Project has enabled scientists to identify many genes involved in causing human disease.  Many questions about genetic diseases can be researched using DNA and gene databases.   In this activity, you will use some of these databases to research and learn more about a genetic disorder.

Huntington’s disease is one of a few dominant disorders in humans.  Individuals with the Huntington’s gene only need one copy of this allele to express this disease.  It is not expressed in an individual until later in life, and can therefore be passed onto an individual’s offspring.  You will use the procedure below to find out more about this disease.

Procedure

1. Access http://www.ncbi.nlm.nih.gov/ .  NCBI stands for National Center for Biotechnology Information.
2. Scroll down the right side of the page under Hot Spots and click on “genetic diseases.”  This is actually the name of the text: Genetic Disorders.
3. Select “full content”, and then scroll down to the “Nervous System.”
4. Under “Nervous System”, select “Huntington’s Disease.”
5. Read the description of Huntington’s disease and answer the following questions:
1. Which chromosome is the gene for this disease found on?
2. Which protein does this gene code for?
3. This mutation is caused by a lengthening of a repeated set of nucleotide triplets – CAG.  Why might a parent’s offspring have an earlier onset of the disease than the parent had?
4. What is the incidence of this disease? (how often and in whom does it occur?)
5. How does a parent know whether their offspring have received the gene for this disorder?
6. Return to the NCBI homepage: http://www.ncbi.nlm.nih.gov/ . 
7. Scroll down the left side of the page and click on the link to “OMIM.”  OMIM stands for Online Mendelian Inheritance of Man.  This is a catalog of genetic diseases.   Search the OMIM database for “Huntignton’s.”
8. Click on the first result, “Huntington’s Disease; HD”
9. Use the information in this database to learn more about Huntington’s disease and answer the following questions.

• What are some of the symptoms associated with Huntington’s disease?
• Read about the inheritance of the disease. Briefly describe the two different types of inheritance of the disease according to the work of Wallace and Hall and Myers.  Be sure to explain how they may be inherited and how the expression of the disease may be effected.
• What are some questions that you may still be wondering about this disorder? 

1. Some questions you may wish to ask can be answered using other resources on the NCBI page.
2. Return to the NCBI homepage.  At the top of the page, click on “All Databases.”  Scroll down and click on “MeSH.”  With this tool, you can search for vocabulary you may be unfamiliar with.  Use this database to find more information about chorea, which is a characteristic of Huntington’s disease.

• What is chorea or choreic movements?
• What are some other diseases you could research using these tools?
• What are some questions you may have concerning these diseases that could be answered using the databases you used today.

Module 9    Answers to Huntington’s disease Questions:

• Chromosome number 4
• Huntingtin
• As the gene is passed on, the CAG repeat can lengthen.  As this repeat lengthens, the onset of the disease occurs earlier in life.
• About 30,000 Americans have it and about 150,000 are at risk of inheriting it.
• A new test can determine whether an individual will develop the disease.
• Symptoms include chorea, rigidity, and dementia, and seizures.  These symptoms tend to progressively worsen after onset of the disease.
• There may be two forms of the disease.  One may have early onset, and one may have late onset.  The late onset expression of the gene may occur more frequently when it was passed on from the mother, and the early onset may occur when it was passed on from the father.   (the authors of the study determined that this may be caused by a heritable extrachromosomal factor, such as mitochondrial DNA.)
• Possible questions?  What are choreic movements (chorea)?  What is the role of Huntingtin in the brain?
• Chorea or choreic movements are involuntary, rapid, jerky movements.  The movements may be subtle, but do not follow normal patterns of movement.
• Students may list any genetic diseases.
• Students may choose similar questions or have other questions about disease symptoms, incidence or inheritance.