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.Team – C2GK

•Area of Science: Microbiology

Team Members:

Christopher Alme Charles Galt Greg Marez

Karen Glennon

Gene Based Diseases

Future Generations

and

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.”

Reviewed by: A.S.A.M editorial. Previously reviewed by Jacqueline A. Hart, M.D., Department of internal medicine, Newton-Wellesley Hospital, Harvard University.

The sickle cell gene is passed fromgeneration to generation in a patternof inheritance.

People with sickle cell trait have one gene for the disease. They are considereda carrier of the trait (heterozygous for thesickle cell allele).

People with sickle cell anemia have twogenes for the disease – one from eachparent (homozygous recessive for thesickle 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

C C

C CC CC

C CC CC

C c

C CC Cc

C CC Cc

C c

C CC Cc

c Cc cc

c c

c cc cc

c cc cc

c c

C Cc Cc

C Cc Cc

CC -- Homozygous Dominant - 0 NonCarrierCc – Heterozygous - 1 CarrierCc – Homozygous Recessive - 2 Diseased

Genotype Possibilities (Punnet Squares)

Computer ModelMonte 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

Non-CarriersCarriersDiseased

Number Of Generations

Nu

mb

er O

f H

um

ans

x 10

00

InitialCarriers = 780Diseased = 20Non-Carriers = 9200

FinalCarriers = 604Diseased = 10Non-Carriers = 9386

(not significantly different)

Effects of Monte Carlo Simulation

0

50

100

150

200

250

0 5 10 15 20 25 30 35

Generations

# o

f D

isea

sed

Run 2

Run 3

Run 4

Run 5

Run 1

Results

Initial ValuesC=7800NC=92000D=200Pd = 0.0Gen = 30

Initial ValuesC=2000NC=0D=20000Pd = 0.5Gen = 30

Non-CarriersCarriersDiseased

Results

Number Of Generations

Nu

mb

er O

f H

um

ans

x 10

4

Marriage Effect On Diseased

0

20

40

60

80

100

120

140

160

180

200

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Probability of Dying If Infected

# o

f D

ise

as

ed

Pe

op

le 0

0.5

1

P(no marriage)

Results

Initial ValuesC=7800NC=92000D=200Pd = 0.0Gen = 30

Effect of Non Marriage of Carriers

0

20

40

60

80

100

120

140

160

180

200

0 0.2 0.4 0.6 0.8 1 1.2

Prob ( Non Marriage)

Dis

eased

Peo

ple Initial Values

C=7800NC=92000D=200Pd = 0.0Gen = 30

Results

Run The Model...

Conclusions

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.

What We Learned……

• “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, 2006Reviewed 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

Software and References

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!!