Transcript Anticipation and Huntington’s Disease

Anticipation and
Huntington’s Disease
William Fergus
5/9/00
What is Huntington’s Disease?
• A degenerative brain disease
• Usually beginning in mid-life, cells in the brain
(i.e., basal ganglia) die, causing deterioration of
intellectual ability, emotional control, balance and
speech.
• Chorea, which means involuntary movements, is
nearly always a symptom as well.
What is Huntington’s Disease?
Huntington’s
Unaffected
• Neurotransmitters in
the basal ganglia are
largely responsible for
motor skills and
balance
• When one pathway is
damaged, neural
signals travel through
other pathways,
causing symptoms
How is it Inherited?
• Autosomal Dominant
• Closely related to the IT15 gene located on
the chromosome 4p16.3 which codes for a
protein named huntingtin.
The Genetic Imperfection
• “Triplets” consist of 3 nucleotides consecutively repeated
(e.g., CAG CAG CAG CAG) a region of DNA.
• All possible combinations of nucleotides are known to
exist as triplet repeats, although some are more common
than others.
• In unaffected people, the gene IT15 will contain between
11 and 34 repeats of the triplet CAG. The CAG triplet
encodes the amino acid glutamine. Therefore, the number
of CAG triplets in gene IT15 equals the number of
glutamine amino acids in the huntingtin protein.
The Genetic Imperfection
• In affected people, there are between 37 and 121 repeats of
the CAG triplet.
• This is commonly called a “stutter.”
• A person who has between 37 and 41 repeats may develop
some of the symptoms of HD, but not necessarily the fullblown disease.
• People who have over 41 repeats almost always develop
the disease.
• The more repeats they have, the earlier the onset, and the
worse the symptoms are.
Anticipation
• Most repeats that are long enough to cause disease are
unstable and have a tendency to get longer with each
successive generation.
• The longer the expansions are, the earlier symptoms arise
or the more severe these symptoms become.
Anticipation
• In some disorders, the expansion produces more of a toxic
gene product. This is likely to occur in Huntington’s
disease.
• For other repeat disorders, the expansion results in less
transcription from the affected gene, and as a consequence,
less of the functional protein is produced. Fragile X is an
illness that exemplifies this type of mechanism.
Pedigree
Sources
• http://www.macalester.edu/~psych/whathap/UBNRP/Huntington/neur
o.html
• http://info.med.yale.edu/chldstdy/plomdevelop/genetics/99decgen.htm
• http://www.interlog.com/%7Erlaycock/what.html
• http://www.geneclinics.org/profiles/huntington/details.html