1. Welcome to the Ellis van Creveld
Museum
The Gene
Hedgehog
Proteins
Pathway
Games!
Museum Entrance Exit
Around the
World

2. Nina, Ninosca, Morgan, and Surui thank you
Curator’s Office
for visiting!
We hoped you learned that Ellis van Creveld is a very interesting genetic disorder
showing you how the founder effect works in a human population as well as
showing the development of the affected individuals. People with this disorder
show abnormalities in all regions of the body which means that this gene plays a
vital role in the major development of our bodies. Since the exact location of the
EVC and EVC2 protein are not well known it is important for research to continue.
The implications of this gene could help us get a better understanding of how
humans develop in the embryo as well as how any abnormal growth occurs.
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Entrance

3. The Gene
Games
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4. Hedgehog Pathway
Way of Life
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5. Proteins
Clothing
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6. Games!
Food
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7. EVC Around the World
Homes
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8. EVC and EVC2 Expression
-Ellis van Creveld syndrome affects many different parts of the body including
tissues, organs, and skeletal structure
--The three main features after birth include
-extra fingers in hands or feet (polydactyly)
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-short stature and shorter arms, legs, or ribcage Exhibit
-Dysplasia in teeth, hair, or nails
-The table above shows the expression of these genes in different organs of
the body

9. EVC the Introduction
- There are actually two genes that are responsible for Ellis van Creveld
syndrome, but both do not count for all the reported cases
- The genes, EVC and EVC2 are both located on the 4th chromosome in
the 16.1 and 16.2 position (as indicated by the yellow arrow)
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Exhibit
Overview Paper: http://www.biomedcentral.com/content/pdf/1750-1172-2-27.pdf&embedded=true

10. Why is it Important?
-The genes involved in Ellis van Creveld syndrome do not account for all the
differences in this genetic disorder meaning that there can be more at
work to create the disorder
-Since these genes tend to affect many of the major organs in the body it is
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Exhibit important to understand the pathway of this disorder
-Ongoing research also shows that a disrupted hedgehog pathway (a
mutation caused by these genes) can also cause cancer, further study of
this gene can lead to a better understanding and treatment options for
cancer

11. How the Pathway Works
-When the Hedgehog ligand
attaches to the Patched
protein a cascade of signals
are sent in the cell that
ultimately lead to the
activation of Ci, a factor that
helps for the hedgehog
target to be transcribed for
replication
-A more molecular view is
available here:
-http://www.dnatube.com/video/58
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Exhibit

12. Hedgehog Pathway
-EVC and EVC2 are novel proteins
important in the creation of
purmorphamine (an agonist of
Smoothened, the regulator of the Ihh
pathway).
-This pathway is important in cell
differentiation and organ development
in embryos
-Both EVC and EVC2 are cilia
transmembrane proteins
-The underproduction caused by a
disruption in the pathway can lead to
malformed organs or skeletal
structures while the stimulation of the
pathway can lead to tumor growth
-This also plays a role in the regulation of
stem cells in the adult human body
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ExhibitPaper :http://www.biomedcentral.com/1741-7007/9/14/
More on Embryonic Development: http://www.biooncology.com/research-education/hedgehog/overview/embryonic/index.html

13. Hedgehog Ligands
-There are three different ligands for the
Hedgehog pathway available in a human
and each have their own specific reaction
when they reach the end of the signaling
pathway
-Sonic Hedgehog (Shh): shown to alter limb
and heart formation
-Indian Hedgehog (Ihh): shown to alter bone
development
-Desert Hedgehog (Dhh): shown to alter
ganglia and intestines
-EVC and EVC2 do not code for the ligands This picture shows the hedgehog gene in
drosophila development (the top is
only for a regulatory component in the the normal type)
pathway that allows each of these ligands
to be processed for their ultimate function Return to
Exhibit
Detailed Paper on Pathway: http://www.abcam.com/index.html?pageconfig=resource&rid=10858&pid=10039

14. The Leucine Zipper
-EVC codes for a 992 amino acid
protein which contains a leucine
zipper. Mutation leads to the
creation of proline amino acid that
leucine, which is important
-A leucine zipper is a transcription
factor that regulates DNA
transcription
-EVC plays a role in the hedgehog
pathway regulation one of which is
hypothesized to be this DNA
leucine zipper formation
-With an improper attachment to the
DNA, the targeted cell’s DNA is not
duplicated for the end products of
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the targeted cell development
Exhibit
Leucine Zipper and DNA implications: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC450290/pdf/emboj00004-0235.pdf

15. You sure are smart
Sonic Hedgehog, Indian Hedgehog, and Desert
Hedgehog are all different hedgehog Return to
pathway ligands found in humans. Aren’t Games
hedgehogs already prickly? We don’t need
anymore prickly things.

16. Limbin
-EVC2 codes for a protein called Limbin
-This limbin molecule is shown to have a role in
regulation of the hedgehog pathway
although it is not entirely understood
-It is believed that this protein acts as a signal
carrier because it is found in both the
nucleus of the cell and the basal portion of
the cilia
-EVC2 can also affect signaling because it
facilitates the attachment of EVC to the cilia
-Any disruption a the signal pathway can lead
to defects that depend on the ligands
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Exhibit
Paper on Cilia and Regulation:
http://www.biomedcentral.com/1741-7007/9/14

17. Which one is NOT a Hedgehog Pathway
Ligand?
ndian Hedgehog Sonic Hedgehog
Prickly Hedgehog Desert Hedgehog
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Exhibit

18. Name this structure
Leucine Zipper
Hedgehog
Ligand
Hedgehog
Pathway
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19. You mean to tell me you didn’t look
around enough?
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Exhibit

20. Which one of these is NOT an effect of
EVC and EVC2?
Abnormal Extra Fingers Tall Stature
Skeletal
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Growth Exhibit

21. Variance of Ellis van Creveld
-This disorder has a 25% pattern of rs735171
AAGAGGGCTCAGGTGT/CCCTCTCCT
inheritance GCTCTCT
-There are more than 2000 different
rs748233
mutations for both portions of the EVC CCCCACTCCCAGCCAC/TGCCCAGCT
gene each containing two different CAGGCCT
alleles rs752061
-This is a very novel disorder that seems TTGAGCCTTGCCCCAC/TCCCCACCC
to show about 150 cases a year, but CAGGGTC
many new cases have been reported Some of the DNA sequencing
even outside of the normal Amish
mutations of this disorder
communities where it is prevalent
show that the bases
highlighted are switched
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Exhibit

22. Distribution Map
Around the World Data
The following is a link to an in general, population:
interactive map for the --.07/100,000 live
distribution of Ellis van births
-5.2/100,000 live
Creveld births in the United
http://www.zeemaps.com/p Arab Emirates
ub?group=439061 -500/100,000 live
births in the Amish
of Pennsylvania
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Exhibit
births in Sweden
parental consanguity in
30% of cases

23. Founder Effect and Ellis van Creveld
-Found effect shows that a certain few leave the population to go colonize
in the other
-With each new population the risk of recessive gene mutations increases
-Ellis van Creveld is an autosomal recessive gene and is prevalent in the
Amish communities
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-The Amish migrated in small colonies and show the same signs of the Exhibit
founder effect
-PBS knows the Amish:
http://www.pbs.org/wgbh/evolution/library/06/3/l_063_03.html

24. You sure are smart
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That is the leucine zipper which is one of the Games
products from the protein EVC codes for.

25. You sure are smart
Extra fingers and abnormal skeletal
structure are definitely products of this Return to
disorder however being tall is Games
definitely not one of them. People
with this disorder are categorized as
having a small stature