Transcript Cc - Supercomputing Challenge

Gene Based Diseases and Future Generations.
Team – C2GK
•Area of Science: Microbiology
Team Members:
Christopher Alme
Charles Galt
Greg Marez
Karen Glennon
Gene Based Diseases
and
Future Generations
Gene Based Diseases and Future Generations.
Problem
There are many diseases today that are linked to a
gene passed from a parent to a child.
Examples of such diseases are sickle cell anemia
and diabetes.
We developed a model to trace the evolution of a
genetic disease through a controlled population over
multiple generations.
Gene Based Diseases and Future Generations
Significance
We looked at the effect of mortality rates on prevalence,
based on inherited diseases in the families. We also looked at
the effects of neo-natal screening and familial counseling.
Methods
We looked at the spread of a particular gene through a
population of 5000 couples as it grows through 30 generations.
We built a Java model that shows how genes spread
through the population and affected mortality
Sickle Cell Anemia
Sickle cell anemia is an inherited disease in which the red blood cells,
normally disc-shaped, become crescent or sickle shaped. The
sickling is caused by the substitution of a single amino acid in the
hemoglobin molecule. This substitution distorts the quaternary
structure of the hemoglobin molecule which in turn changes the red
blood cell from its typical “discoid” shape to the sickle shape that is
seen in the blood smears of carriers of the trait. This distorted
hemoglobin molecule does not bind oxygen well, tends to attenuate
faster than normal, and will accumulate, particularly in the spleen.
Also, these cells function abnormally and cause small blood clots.
These clots give rise to recurrent painful episodes called “sickle cell
pain crises.”
The sickle cell gene is passed from
generation to generation in a pattern
of inheritance.
People with sickle cell trait have one
gene for the disease. They are considered
a carrier of the trait (heterozygous for the
sickle cell allele).
People with sickle cell anemia have two
genes for the disease – one from each
parent (homozygous recessive for the
sickle cell allele).
Reviewed by: A.S.A.M editorial. Previously reviewed by
Jacqueline A. Hart, M.D., Department of internal medicine,
Newton-Wellesley Hospital, Harvard University.
Two carriers have a 25% chance of having an unaffected child, 50% chance of
having a child who is a carrier, and a 25%
chance of having a child with sickle cell
anemia
Genotype Possibilities
(Punnet Squares)
C
C
C
CC
CC
C
CC
CC
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cc
cc
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cc
cc
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C
Cc
Cc
C
Cc
Cc
C
c
C
CC
Cc
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Cc
cc
C
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C
CC
Cc
C
CC
Cc
CC -- Homozygous Dominant - 0 NonCarrier
Cc – Heterozygous
- 1 Carrier
Cc – Homozygous Recessive - 2 Diseased
Computer Model
Monte Carlo method of modeling was used to
 Select couples that reproduce.
 Determine offspring genotype.
 Determine whether or not the disease person survives.
(probability of death)
 Determine whether of not a carrier (heterozygous &
homozygous recessive) mate.
(probability of non marriage)
Model was written in Java
Models runs
• Default run
• Effect of the Monte Carlo techniques on
the default run
• Effect of probability of death
• Non Marriage effect
Results
Number Of Humans x 1000
Non-Carriers
Carriers
Diseased
Initial
Carriers = 780
Diseased = 20
Non-Carriers = 9200
Final
Carriers = 604
Diseased = 10
Non-Carriers = 9386
(not significantly different)
Number Of Generations
Results
Initial Values
C=7800
NC=92000
D=200
Pd = 0.0
Gen = 30
Effects of Monte Carlo Simulation
250
# of Diseased
200
Run 2
150
Run 3
Run 4
Run 5
100
Run 1
50
0
0
5
10
15
20
Generations
25
30
35
Results
Number Of Humans x 104
Non-Carriers
Carriers
Diseased
Initial Values
C=2000
NC=0
D=20000
Pd = 0.5
Gen = 30
Number Of Generations
Results
Marriage Effect On Diseased
200
# of Diseased People
180
P(no marriage)
160
0
140
0.5
Initial Values
C=7800
NC=92000
D=200
Pd = 0.0
Gen = 30
1
120
100
80
60
40
20
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Probability of Dying If Infected
0.9
1
Results
Effect of Non Marriage of Carriers
200
180
Diseased People
160
Initial Values
C=7800
NC=92000
D=200
Pd = 0.0
Gen = 30
140
120
100
80
60
40
20
0
0
0.2
0.4
0.6
0.8
Prob ( Non Marriage)
1
1.2
Run The Model...
Conclusions
What We Learned……
How to use punnet squares.
We learned about sickle cell anemia.
Cycle sickle anemia may not change if current practices
remain the same.
There appears to be a cyclical phenomenon in the
model.
Software and References
•
“Mortality among children with sickle cell disease identified by newborn screening during 19901994” March 13,1998, Morbidity and Mortality Weekly Report
http://www.findarticles.com/pp/articles/mi_m0906/is_n9_v47/ai_20403697/print
July 24,2006
•
“Mortality in sickle cell disease; Life expectancy and risk factors for early death”
http://www.ncbi.nlm.nih.gov/entrez.fcgi:cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=799
3409 July 24, 2006
•
“Sickle Cell Anaemia” 2006, by Ashok Raj,MD,
http://www.emedicine.com/PED/topic2096.htm July21,2006
•
“Sickle Cell Anemia; Hemoglobin SS disease (Hb SS)”
http://www.nlm.nih.gov/medlineplus/ency/article/000527.htm July 24, 2006
Reviewed by: A.D.A.M editorial. Previously reviewed by Jacqueline A. Hart, M.D., Department of
Internal Medicine, Newton-Wellesley hospital, Harvard University.
•
“Sickle cell anaemia and S-thalassemia in Sicilian children”, 1992, by Giovanna Russo and Gino
Schiliro. http://www.sicklecellsociety.org/information/resrep/res14.htm July 21,2006
•
“United States Birth Rate Information” CIA World Fact Book, January 1, 2005,
www.indexmundi.com/g/g.aspx?c=us&=25 July 24, 2006
Acknowledgements
Our special thanks to Nick Bennett for his help in completing the Java programming
and Bryan Lewis for all of his input.
Thank you to Celia Einhorn for her help in putting things in perspective and
keeping us on task.
We appreciate the support and encouragement from David Kratzer, Willard Smith,
Betsy Frederick, PB&J Irene Lee, Dale Henderson, James Taylor (even if he didn’t
sing), Hal Scheintaub (especially for cooking), and Dylan Allergretti.
This is a wonderful opportunity!!