Gene Based Diseases and Future Generations. Team – C2GK

1. Gene Based Diseases and Future Generations.Team – C2GK • Area of Science:Microbiology Team Members: Christopher Alme Charles Galt Greg Marez Karen Glennon

2. Gene Based Diseases and Future Generations

3. 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.

4. 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

5. 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.”

6. 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.

7. Genotype Possibilities (Punnet Squares) CC -- Homozygous Dominant - 0 NonCarrier Cc – Heterozygous - 1 Carrier Cc – Homozygous Recessive - 2 Diseased

8. 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

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

10. 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

11. Results Initial Values C=7800 NC=92000 D=200 Pd = 0.0 Gen = 30

12. Results Non-Carriers Carriers Diseased Number Of Humans x 104 Initial Values C=2000 NC=0 D=20000 Pd = 0.5 Gen = 30 Number Of Generations

13. Results Initial Values C=7800 NC=92000 D=200 Pd = 0.0 Gen = 30

14. Results Initial Values C=7800 NC=92000 D=200 Pd = 0.0 Gen = 30

15. Run The Model...

16. 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.

17. 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/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=7993409 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.htmJuly 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

18. 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!!