Huntington�s Disease: A Genetic Disorder
Andrew
Maloney
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.
Works
Cited
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