PARKINSON'S DISEASE RESEARCH -- HANNAH FINK
1. DNA (deoxyribonucleic acid) History
In 1953, Rosalind Franklin, Francis Crick, and James Watson collected x-ray diffraction
data. They created the structure of the double helix and wrote a paper called “Molecular
Structure of Nucleic Acids: A Structure of Deoxyribonucleic Acid.” In 1868, the University of
Tubingen, Johannes Friedrich Miescher experimented leukocytes and their chemical
composition. He found a new type of cellular material. It was not a protein and had a large
amount of phosphorous. He named it nucleic acids. He later proved that nucleic acids were part
of all cell nuclei. Albrecht Kossel, a German professor, found that nucleic acids had protein and
non-protein parts and they produced carbohydrates and nitrogen-bearing compounds. They were
the bicylic purines: guanine and adenine and the monocylic pyrimidines: thymine, cytosine and
uracil. Scientists were trying to discover DNA’s function as well as its structure and where the
genetic information was stored.
2. Scientific breakthroughs developed due to knowledge of the DNA structure
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Frederick Griffith – 1928: Discovered heat-killed, disease-killing bacteria, contains the
ability to change bacteria that is harmless into bacteria that causes disease.
Oswald Avery – 1944: Treated and extract from heat-killed bacteria with enzymes to
break down proteins, lipids, carbohydrates and RNA but transformation happened
anyway. They tried again but used an enzyme to destroy DNA instead. Transformation
did not occur and they had discovered that the transforming factor is DNA.
Rosalind Franklin – 1952: Her discoveries indicated that DNA has a helical structure
James Watson & Francis Crick – 1953: Build 3-D models of DNA with wire and
cardboard. It was not until they saw Franklin’s x-ray patterns that their models were
correct. Eventually they were able to build a DNA double helix structure model.
Sydney Brenner – 1960: Discovered and showed (proved) the existence of mRNA
(messenger RNA).
Walter Gilbert – 1977: Discovered methods to be able to read the sequence of DNA.
Human Genome Project – 2000: In progress for 13 years. Was an attempt to sequence all
DNA from humans. Completed in 2003.
3. Explanation of DNA replication
The enzyme DNA Helicase "unzips" the DNA double helix, breaking the hydrogen bonds
that hold the nitrogen bases together. Enzymes are added to the two separated strand
portions so that the strands do not twist around and come back together. The two areas on
either end of the DNA where the double helix separates are called replication forks. DNA
polymerase glides along the exposed strands, adding complementary nucleotides to the
existing ones. DNA polymerase remains attached until all DNA has been copied and is
signaled to detach. When DNA polymerase is done, two identical strands of DNA have
been formed- each containing one old strand and one new strand. The nucleotide
sequences in both DNA molecules are identical to each other and to the original DNA
molecule. Side note: In DNA replication, mutations can sometimes occur when the wrong
nucleotide is added. DNA polymerase can backtrack, remove the wrong nucleotide, and
add the right one. This makes it able to "proofread" its work.
4. How mutations cause disease
Gene mutations are a permanent change in the DNA sequence that makes up a gene. A
mutation can occur two different ways: They are inherited from a parent, which are
known as hereditary or germline mutations or attained during your lifetime, which occurs
in almost every cell in the body. The reason why some people are affected by a mutation
without having any family history of the disease that it causes it because a mutation
called a “new mutation” happens in an egg or sperm cell right after fertilization.
Acquired, or somatic, mutations happen during the person’s life within their cells. There
a few reason why this happens, the first being the environmental factors (ultraviolet
radiation from the sun) or if when DNA copies itself during cell division but makes a
mistake. They cannot be passed down to other generations. An early embryo is another
place a mutation could occur. A mosaicism is a mutation where the person will have
some cells with the genetic change and some without it whenever the cells divide during
growth and development.
1. Deletion: genetic material is deleted or removed (either complete or partial
chromosome loss)
2. Frame shift: number of bases (that is not a multiple of three) are inserted or deleted,
results in premature stop codon.
3. Insertion: insertion of one or more bases and genetic material put into another DNA
region.
4. Missense: DNA sequence changed codon to a different amino acid.
5. Nonsense genetic code change in the coding for a stop codon instead of an amino acid
6. Point: one change in DNA sequence, can be silent, missense, or nonsense
7. Silent: genetic sequence is changed but the protein sequence stays the same.
8. Splice Site: change at the boundary of exons and introns, consensus sequences at signal
where to cut out introns and rejoin exons in mRNA
9. Translocation: chromosomes are structurally abnormal where non-homologous
chromosomes and genetic materials are exchanged
5. Disease that your models illustrate and the type of mutation that causes the disease
Parkinson's is a disease that has been known about since the ancient times. It was
described by the physician Galen as "shaking palsy" within Western medical literature in
AD 175. However, a detailed medical essay was not published on the disease until 1817
by James Parkinson, a London doctor. In the essay, called "An Essay on the Shaking
Palsy," was based on six cases James Parkinson had observed within is personal practice
and walks around his neighborhood.
Sixty years after it was published, Jean Martin Charcot, a French neurologist, perceived
the essay as encouragement to further study the disease. Charcot was the first person to
realize the importance of Parkinson's work and even named the disease after him.
There are many things about Parkinson's disease that still remains a mystery. The
symptoms usually occur in older people and are degenerative (a gradual deterioration)
and progressive. Scientists had an idea that it was a dopamine deficiency in the brain that
is the root of the disease, but did not understand why it happened.
In the 1960s, brains of individuals with Parkinson's were compared to brains of
individuals without and differences were taken note of. Degeneration of nerve cells was
caused by low levels of dopamine in a part of the brain called the substantia nigra.
Because of this discovery, a medicine called Levodopa was synthesized to treat the
symptoms.
Even though there is no cure for Parkinson's, research has not stopped and symptoms can
be controlled and the severity lessened. In 1957, The Parkinson's Disease Foundation was
created to fund more research and support patients. One of the most recent notable
foundations made is the Michael J Fox Foundation, named after the actor, and has made
over 90 million dollars since 2000.
My models will illustrate Parkinson’s disease. The cause of Parkinson’s is the result of a
mutation in the SNCA gene. My models will show the mutation of the PARK1 gene on
chromosome 4q22.1.
Model Coding for PARK1 Gene
http://www.genecards.org/cgibin/snps/snp_link.pl?rs_number=104893877&file=/home/genecards/current/old_website/
cards_usr/entries/SN/card_SNCA.txt;&kind=ExpressionData;&chrom=4
PARK1 Gene Information/Location
http://www.bio.davidson.edu/courses/genomics/2001/madden/assignment1.html
http://omim.org/entry/168601
PARK Gene Family
http://ghr.nlm.nih.gov/geneFamily/park