Case Study 3: Werner

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Case Study 3 Werners Syndrome a progeriac
disease
Cell Division Cell Cycle
Aging
What mechanisms control the proliferation of
cells?
What governs the life span of an organism?
Cell death as a necessary and important part of
development Apoptosis (programmed cell death,
pcd)
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Context George Martin, 1978
Genetic Syndromes in Man with Potential
Relevance to the Pathology of Aging
lt 7000 genes involved in degenerative processes
associated with aging
Between 70 and 7 genes control processes having
large impact on senescence
What is cell senescence?Divide certain of
times then enter G0 and eventually die
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Aging a multigene process
10 genetic diseases that mimic aging processbut
only in part
Chromosomal aneuploides? Downs syndrome
Dementia, cataracts, diabetes, hair graying,
cancer
Known single mutant gene?Werners syndrome
Skin thinning, Hair graying and loss,
atherosclerosis, Cataracts, cancer diabetes,
osteoporosis
Unknown but thought to be single gene?
Hutchinson-Gilfords Progeria
Skin thinning hair loss, atherosclerosis,
osteoporosis, hypertension
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Werners Syndrome
www.pathology.washington.edu/werner/
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Werners history
Named for C. W. Otto Werner (1879-1936) Rural
doctor, medical officer in German Navy WWI Rare
autosomal recessive disease Approx 1 in 200
people carriers for defective gene Approx 3 in
1,000,000 people have the disease (Slightly
higher percentage in Japan) Onset of symptoms
early to mid 20s, Major cause of deathheart
attack in mid 40s
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Cells of Progeria and WS
Cell Culture What do cells need to proliferate?
When compare fibroblasts of child with Progeria
and their parent Childs cells are older in
terms of replication
Progeriac Fibroblasts Rarely ever double Few
cell generations before death
Note Often Progeriac used to describe any
premature aging as well as the specific disorder
Hutchinson Gilford Progeria
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Why do we age?/How how do we age?
Short answer Dont know
The 3 Rs Mutation effecting DNA reading,
replicating or repair
3 Hypotheses for Aging
1) Free Radical Theory Aging due to accumulation
of damage from free radicals
2) Telomere Theory Chromosome ends shorten with
divisions
Cause of Werners syndrome
3) Helicase defect Mutation Chromosome 8 in WRN
gene all 35 known mutations result in truncated
protein all remove nuclear targeting
sequence different muts associated with
different cancers
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Case Study Focuses
Cell death damage and apoptosis
Telomeres and replication
Cell Cycle and its regulation
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Lab to wrap up by end of this week No new setup
after Thursday so all data in by Sunday
REVISED DEADLINES Stretched and divided No flow
chart turned in (although still a good idea to
make one) Before Nov 21st 5pm (Tuesday) Half
of group posts Intro, Results References, other
half posts Results, Discussion, References (see
table to find out what you are writing and
instructions for every section) Before beginning
of your lab on week of Nov 27th Group members
print specific section sections and revise. Keep
the version with comments on it, post the
revised version. You will have time to meet as a
group during the lab period (see table to see
what you are revising and instructions for
reviewing/revising) Before December 5th at noon
(Tuesday) Groups meet and develop one article
containing Title, Abstract, Intro, Results
Discussion, Experimental Procedure and
References. Each persons version with comments
and the final group article is submitted as a
portfolio for evaluation. The drafts and
comments will be indications of level of
participation. I will evaluate the final
product.
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Therefore
Each PERSON posts 1/4 draft they wrote edits a
draft and turns in the copy they wrote
on posts 1/4 draft another wrote and
they edited/revised Each GROUP turns in a
full lab article (not ea. person) hard
copy Whole group follows process that is more
similar to published article writing (and is done
in more manageable pieces)