Huntington�s Disease: A Genetic Disorder
1st year Biology student at the University of Chicago
Near the end of the short arm of chromosome four, there exists a gene which can cause an individual to experience three completely different lives.� If the gene is expressed normally, one will never know, as it will not cause the person any harm.� However, if the gene simply does not exist, the individual will be born with Wolf-Hirschorn Syndrome, a devastating illness which causes disfigured facial features and mental retardation. (Ridley, 55)� Victims of this syndrome rarely live past the age of seven.� The last and most interesting situation occurs when this gene becomes mutated.� In this case, the individual will suffer from Huntington�s Chorea, a debilitating neurological disease which will not show its effects until mid-life.� Because of this disorder, the gene is known as �The Huntington Gene,� though it has also been referred to as �The Wolf-Hirschorn Gene� and �IT15� meaning �Interesting Transcript #15.��
The Huntington Gene codes for a protein known as huntingtin.�� This protein carries the amino acid glutamine, which aids in a variety of metabolic processes.� In fact, �the repetition of the �word� �C A G� in the middle of the (Huntington) gene results in a long stretch of glutamines in the middle of the protein� (Ridley, 58).� The excessive repetitions of �C A G� thus express an excessive number of glutamines within the huntingtin proteins.� The extra glutamine found in these proteins slowly clump together in the movement-control cells of the brain.� Matt Ridley, author of the book Genome, believes that this sticky mass of protein kills the cell by making it commit suicide. (59)� The normal huntingtin protein was found by Dr. Elena Cattaneo at the University of Milan to regulate the production of BDNF, a chemical found in the brain which is necessary for keeping striatal nerve cells functioning. (Huntington�s Disease Society of America � Yearly Update)� Thus it seems that it is simply the extra huntingtin proteins caused by mutation which negatively affect the cells of the body.
Those afflicted with Huntington�s Disease generally begin to exhibit problems with their �control of bodily movements, intellectual functioning and emotion(s)� (Fact Sheet: Huntington�s Disease).� The disease generally begins to affect the individual around the age of fifty, though it can occur much earlier.� The victim will usually suffer for ten to twenty-five years before succumbing to complications of the illness, generally heart failure or aspiration pneumonia (Fact Sheet: Huntington�s Disease).
The area of the Huntington Gene which is known to mutate contains only one �word� each consisting of three �letters� as Ridley explains (55).� The repetition of the bases �C A G� throughout the gene can occur anywhere from once to over one hundred times.� The number of repetitions determines whether or not an individual sees the effects of the disease and at what age the symptoms begin.� The mutated form of the gene arises when an excessive number of �C A G� repetitions occur.� The average number of repeats for a normal Huntington Gene is between ten and fifteen (Ridley, 55).� A study presented by Dr. Kathleen Shannon at the General Meeting of the Illinois Chapter of the Huntington�s Disease Society of America on March 7, 1997 concluded that there are specific numerical cut-offs for having Huntington�s.� If an individual has less than thirty repetitions, they do not have Huntington�s Disease.� However, more than forty repetitions will always result in the disease.� There exists a gray area between thirty and forty which is now under intense study.� Scientists are trying to find why some individuals with thirty-nine repetitions do not have HD, while others with only thirty-six repeats do.� Dr. Shannon believes that there must be some other factors at work to explain the situation, whether it be another gene, gender, or general health is still under determination.
It is known however, that the number of repeats over forty determines the severity of the disease and the age at which the body begins to exhibit Huntington�s.� As the number of �C A G� repetitions increases, the age at which one shows the symptoms of HD decreases.� In fact, if a gene contains sixty or more repeats, the victim will suffer from Juvenile Huntington�s Disease which strikes individuals in their twenties.
The question which is then presented is how this mutation of excessive repetitions occurs.� It is known that the Huntington Gene undergoes its mutation as its DNA is being replicated.� The longer the strand of �C A G� repeats, the more likely it is for there to be an error in its replication.� This is because the �C� and �G� bases often form small loops of DNA known as �hairpins.�� When these �hairpins� of DNA unzip, a large number of �C A G� �words� must be replicated.� Often times the copying mechanism miscounts the exact number and inserts extra �words� of �C A G� into the new strand of DNA. (Ridley, 60)� This accounts for the coding of extra proteins expressed by the gene.
Huntington�s Disease has two characteristics which make it extremely difficult to disappear naturally.� First of all, the Huntington Gene is dominant, meaning that only one parent needs to have the mutated gene in order to pass it on to their offspring.� Secondly, since the disease does not begin to show its signs until mid-life, often times victims have already reproduced, unknowingly passing on the gene.� Sadly, no cure has yet been found for Huntington�s.� The only way of preventing the disease is to have the chromosomes of parents and potential offspring tested, a difficult and often times unnecessary procedure.
Fact Sheet: Huntington�s Disease. 1996. Retrieved 2 April 2002 from the World Wide Web: http://www.caregiver.org/factsheets/diagnoses/huntingtons.html.
Huntington�s Disease Society of America � Yearly Update. 2001. Retrieved 2 April 2002 from the World Wide Web: http://www.hdsa.org.
Ridley, Matt. (1999). Genome. New York: Harper Collins.
Shannon, Dr. Kathleen. (1997). Huntington�s Disease. In The General Meeting of the Illinois Chapter, Huntington�s Disease Society of America, 7 March 1997.
Created and maintained by Renette Davis with permission from the author. Send comments for Renette to her by clicking here.
Created: July 4, 2002
Last updated: Nov. 30, 2010