Huntingtons Disease

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Huntingtons Disease

• Gabriel A. Molina
• Haley King
• Kristoff Fajardo
• July 26, 2001

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Summary

• Background
• Problems
• Research

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Introduction to Huntingtons Disease

• Huntingtons Disease (HD) is a brain disorder
  that targets the striatum and cerebral cortex.
• The neurons in these areas die and result in the
  following symptoms Movement Disorders, Dementia,
  and eventually death.
• Right now, there is no cure or successful
  treatment for HD.

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The Human Brain
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Ways to Get HD

• HD is a genetic disorder that can be passed down
  from one or both parents by chromatid crossover.
• It is an autosomal dominant disease.

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Chromosome 4 Crossover
Click on picture to play or stop animation
Click on picture to play or stop animation
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Where the Gene is Located

• The Huntingtin gene is located on the fourth
  chromosome.
• Exact location 4p16.3 (2.2Mb)
• Location was determined in 1983.
• The gene is 180,000 base pairs.

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How we can Diagnose HD through PCR

• By changing the applicant(s) mRNA into cDNA and
  PCR-ing it with a CAG repeat primer, we can
  replicate the exact sequence that causes HD.
• After this, we can place the replicated DNA into
  a gel electrophoresis apparatus with a marker
  containing an unharmful amount of CAG repeats.

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How we can Diagnose HD through PCR

• If the applicant(s) CAG repeats are higher than
  the unharmful amount, then they can be diagnosed
  with HD.
• It is easy to compare the DNA sample to the
  marker because a normal amount of repeats is 5-35
  and a person with HD usually possesses around 200
  repeats.

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What the Protein Normally Does

• Although the true function of the huntingtin
  protein is not known, we do know that the
  deformed protein is localized to the nucleus.
• By removing the portion of the gene that
  localizes deformed huntingtin proteins to the
  nucleus, we can observe where the protein travels
  to normally.

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Study of Correlation of Trinucleotide Repetition
Length with Age and Severity

• We can compare the length of the repeats by PCR
  and Gel Electrophoresis. First we take a DNA
  sample from different applicants.
• Then we compare them on a gel electrophoresis
  plate.
• By using some statistics a correlation can be
  found by comparing age or severity of the
  applicants to the length of the repetition.

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Our Mitochondria Theory

• HD also affects the function mitochondria within
  a cell. One theory is that the deformed
  huntingtin protein is somehow attracted to the
  mitochondria because of that fact that
  mitochondria was once a primitive unicellular
  organism that contained a nucleus. The nucleus
  is what deformed huntingtin is localized to.

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Expansion of Trinucleotide in Coding vs.
Non-Coding DNA

• Basically, an expansion in either introns or
  exons will produce deleterious results.
• The difference is in the type of deformation that
  will occur.
• Non-coding region expansion will result in too
  much or too little production of the protein.
• Coding region expansion will result in a
  degenerate or deformed protein.

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Conclusion
As we continue along the road to a cure and move
from exclusively funding basic research into our
new therapeutic directive and clinical trials
arena, we ask for your help. As each year brings
increased opportunities, it must also bring
increased funding. Every dollar donated brings
us one step closer to the cure.