Transcript Case Study 3: Hutchinson-Gilford`s Progeria Syndrome

Case Study 3: Werner’s 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)
Context: George Martin, 1978
‘Genetic Syndromes in Man with Potential Relevance
to the Pathology of Aging’
< 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
Aging a multigene process
10 genetic diseases that mimic aging process—but only in part
Appears
Chromosomal aneuploides Down’s syndrome
Birth
Dementia, cataracts, diabetes, hair graying, cancer
Known single mutant geneWerner’s syndrome
In 20’s
Skin ‘thinning’, Hair graying and loss, atherosclerosis,
Cataracts, cancer diabetes, osteoporosis
Unknown but thought to be single gene
Hutchinson-Gilford’s Progeria
Skin ‘thinning’ hair loss, atherosclerosis, osteoporosis,
hypertension
Helicase
Birth/1yr
??
Werner’s Syndrome
www.pathology.washington.edu/werner/
Werner’s 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 20’s,
Major cause of death—heart attack in mid 40s
Cells of Progeria and WS
Cell Culture
What do cells need to proliferate?
When compare fibroblasts of child with Progeria and their parent
Child’s cells are ‘older’ in terms of replication
Fibroblasts
‘normal cells’ divide ~12 to 24 hours
Divide approx 50times in culture
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
Why do we age?/How how do we age?
Short answer: Don’t know
The 3 R’s: 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 Werner’s syndrome
3) Helicase defect: Mutation Chromosome 8 in WRN gene
all 35 known mutations result in truncated protein
all ‘remove’ nuclear targeting sequence
different mut’s associated with different cancers
Case Study Focuses
Cell death: damage and apoptosis
Telomeres and replication
Cell Cycle and its regulation
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 R
(see table to find out what you are writing and instructions for
Before beginning of your lab on week of Nov 27th
Group members print specific section sections and revise. Keep
(see table to see what you are revising and instructions for revi
Before December 5th at noon (Tuesday)
Groups meet and develop one article containing Title, Abstract
The drafts and comments will be indications of level of particip
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)