Background: Huntington’s chorea is a neurodegenerative disease characterized by motor, cognitive, and emotional symptoms. The age of onset for symptoms is generally 30-50 years. The genetic basis of the disease is an amplification in a gene with an (as yet) unknown function. A triplet (CAG) is repeated 20-50 times in asymptomatic individuals; having more than 50 repeats is associated with disease symptoms. Huntington’s disease is considered a dominant disorder, since one copy of the amplified gene appears to be sufficient to cause disease symptoms. This amplification can be detected by restriction enzyme digestion and Southern blot analysis, since the size of the fragment bound by the probe is increased as a result of the amplification of the triplet repeat. Alternatively, PCR can be used to isolate the region containing the triplet repeats; the relative size of the repeat region can be determined by running the PCR products on a gel.
Case A: Susan is a 23-year-old whose father, age 55, and paternal aunt, age 61, have been diagnosed with Huntington’s chorea. A paternal uncle, age 66, appears to be unaffected by the disease. Susan wants to know if she inherited the mutated gene from her father so that she can prepare for that future if necessary. She arranges to undergo DNA testing for Huntington’s disease. Her 17-year old brother, John, also decides to be tested after talking with Susan.
To run the test, the following DNA samples are amplified by PCR using primers specific for the Huntington’s disease gene.
Control DNA, with HD mutation
Control DNA, normal (no HD mutation)
- What conclusions can you draw from these results?
- What is the status of each person with respect to Huntington’s disease?
- What is the molecular basis of this disease, and why does this result in the observed gel patterns?
- How would you counsel Susan and her brother based on the results of the test?
- What issues are raised by this type of testing?