Gene Based Diseases and Future Generations' Team C2GK

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Gene Based Diseases and Future Generations.Team
C2GK

• Area of Science Microbiology

Team Members Christopher Alme Charles
Galt Greg Marez Karen Glennon
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Gene Based Diseases
and

• Future Generations

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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.
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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
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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.
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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). Two carriers have a 25 chance of
hav- ing 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
Reviewed by A.S.A.M editorial. Previously
reviewed by Jacqueline A. Hart, M.D., Department
of internal medicine, Newton-Wellesley Hospital,
Harvard University.
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Genotype Possibilities (Punnet Squares)
CC -- Homozygous Dominant - 0 NonCarrier Cc
Heterozygous - 1
Carrier Cc Homozygous Recessive - 2
Diseased
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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

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Models runs

• Default run
• Effect of the Monte Carlo techniques on the
  default run
• Effect of probability of death
• Non Marriage effect

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Results
Non-Carriers Carriers Diseased
Initial Carriers 780 Diseased 20 Non-Carriers
9200
Final Carriers 604 Diseased 10 Non-Carriers
9386
Number Of Humans x 1000
(not significantly different)
Number Of Generations
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Results
Initial Values C7800 NC92000 D200 Pd 0.0 Gen
30
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Results
Non-Carriers Carriers Diseased
Number Of Humans x 104
Initial Values C2000 NC0 D20000 Pd 0.5 Gen
30
Number Of Generations
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Results
Initial Values C7800 NC92000 D200 Pd 0.0 Gen
30
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Results
Initial Values C7800 NC92000 D200 Pd 0.0 Gen
30
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Run The Model...
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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.
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Software and References

• Mortality among children with sickle cell
  disease identified by newborn screening during
  1990-1994 March 13,1998, Morbidity and Mortality
  Weekly Report http//www.findarticles.com/pp/artic
  les/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.fcgicmdRetrie
  vedbPubMeddoptAbstractlist_uids7993409
  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/artic
  le/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/in
  formation/resrep/res14.htm July 21,2006
• United States Birth Rate Information CIA World
  Fact Book, January 1, 2005, www.indexmundi.com/g/g
  .aspx?cus25 July 24, 2006

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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,
PBJ Irene Lee, Dale Henderson, James Taylor
(even if he didnt sing), Hal Scheintaub
(especially for cooking), and Dylan
Allergretti. This is a wonderful opportunity!!