1. November 7, 2013
Warm Up: What disease does the protozoan plasmodium cause in humans?
Homework: Finish the meiosis project and have it ready to turn in tomorrow! Textbook Returned?
Class Work: Take notes from PPT on the affect of plasmodium on a genetic mutation in humans called Sickle Cell Disorder.
Question of the day: What determines if a genetic mutation is positive or negative?

2. Sickle cell disorder
A mutation that is good and bad Video

3. Some Genetic History
The error in the hemoglobin gene results from a genetic mutation that occurred many thousands of years ago in people in parts of Africa, the Mediterranean basin, the Middle East, and India.
A deadly form of malaria was very common at that time
Malaria epidemics caused the death of many
In areas where malaria was a problem, children who inherited one sickle hemoglobin gene and who, therefore, carried the sickle cell trait - had a survival advantage.
Unlike the children who had normal hemoglobin genes, they survived the malaria epidemics they grew up, had their own children, and passed on the gene- for sickle hemoglobin.

4. Plasmodium and sickle cell trait
Individuals with sickle-cell anemia or sickle-cell trait do have reduced numbers of parasites when compared to individuals for the normal hemoglobin protein in red blood cells
For individuals with Sickle Cell Trait the plasmodium protozoan has difficulty attaching itself the red blood cells and therefore, they cannot reproduce within the cells. The life cycle of plasmodium is disrupted.

5. Sickle Cell Gene
Severe Malaria

6. History
As populations migrated, the sickle cell-mutation spread to other Mediterranean areas, further into the Middle East and eventually into the Western Hemisphere.
In the United States and other countries where malaria is not a problem, the sickle hemoglobin gene no longer provides a survival advantage.
Instead, it may be a serious threat to the carrier's children, who may inherit two abnormal sickle hemoglobin genes and have sickle cell anemia.

7. Who is at risk? Most common in Africans and African Americans.
East Asia, Southern Italy, Saudi Arabia, India, Egypt, South and Central American, Cuba, the Caribbean, Greece, and Iran, and Eastern Jews have also been found to have a form of this illness.

8. Prevalence More than 2.5 million Americans have the trait
70,000 or more Americans have sickle cell disease
About 1,000 babies are born with the disease each year in America
In Nigeria, 1/3 population of U.S., 45,000-90,000 babies with sickle cell disease are born each year

9. Among African - Americans
1 in 12 have Sickle Cell Trait (Hb SA)
1 in 600 have Sickle Cell Anemia (Hb SS)
1 in 1500 have Sickle C Disease (Hb SC)
1 in 350 have Sickle Cell Disease (Hb SS, SC, S-Beta-Thal)
Among Latinos
1 in 172 have Sickle Cell Trait (Hb AS)
1 in 1,000 have Sickle Cell Disease (Hb SS, SC, S-Beta-Thal)

10. What is Sickle Cell Anemia (SCA)?
First described in Chicago in 1910 by James Herrick as an inherited condition that results in a decrease in the ability of red blood cells to carry oxygen throughout the body
Sickle red blood cells become hard and irregularly shaped (resembling a sickle)
Become clogged in the small blood vessels and therefore do not deliver oxygen to the tissues.
Lack of tissue oxygenation can cause excruciating pain, damage to body organs and even death.
Dolan DNA Learning Center

11. Mechanism Red blood cells (RBC)
Contain a special protein called haemoglobin (Hb)
Hb is the component that carries oxygen from the lungs to all parts of the body
Most people have only hemoglobin type – Hb A within RBC (normal genotype: Hb AA)
Sickle Cell: HbS
S similar to A, but one structural change
Other types: HbC, HbD, and HbE

12. Mechanism -HbS
When sickle haemoglobin (HbS) gives up its oxygen to the tissues, HbS sticks together
Forms long rods form inside RBC
RBC become rigid, inflexible, and sickle-shaped
Unable to squeeze through small blood vessels, instead blocks small blood vessels
Less oxygen to tissues of body
RBCs containing HbS have a shorter lifespan
Normally 120 days
Chronic state of anaemia

13. Genetics HbS –Recessive S=Sickle A=Normal
2 copies of the gene for Hb (each parent)
HbS –Recessive
S=Sickle
A=Normal

14. Sickle Cell Trait Carrier
Sickle haemoglobin (S) + Normal haemoglobin (A) in RBC
Adequate amount of normal Hb (A) in red blood cells
RBC remain flexible
Carrier
Do Not have the symptoms of the sickle cell disorders, with 2 exceptions
Pain when Less Oxygen than usual (scuba diving, activities at high altitude (12,000ft), under general anaesthesia)
Minute kidney problems

15. Three common types of Sickle Cell Disorders Sickle Cell Anemia
Sickle haemoglobin (HbS) + Sickle haemoglobin (HbS)
Most Severe – No HbA
Hemoglobin S-C disease
Sickle haemoglobin (HbS) + (HbC)
Hemoglobin S-Beta thalassemia
Beta thalassaemia gene reduces the amount of HbA that can be made
Sickle haemoglobin (HbS) + reduced HbA
Milder form of Sickle Cell Disorder than sickle cell anemia

16. Screening Haemoglobin Electrophoresis Prenatal Testing Amniocentesis
Simple Blood test
Routine screening in high risk groups
During pregnancy
Before anaesthesia
Prenatal Testing
Amniocentesis
16 and 18 weeks of the pregnancy
small risk of causing a miscarriage (1 in 100)
Chorionic villus sampling (CVS)
9th or 10th week of pregnancy
very small amount of material from the developing placenta
slightly higher chance of miscarriage

17. Symptoms Typically appear during infant's first year
1st symptom: dactylitis and fever (6 mo-2 yrs)
Pain in the chest, abdomen, limbs and joints
Enlargement of the heart, liver and spleen nosebleeds
Frequent upper respiratory infections
Chronic anemia as children grow older
Over time Sickle Cell sufferers can experience damage to organs such as liver, kidney, lungs, heart and spleen
Can result in death

18. Serious Complications: PAIN Recurrent Pain Episodes or Sickling Crises
Occur at any age but appear to be particularly frequent during late adolescence and early adult life
Unpredictable
Red Blood Cells get stuck in the small veins and prevent normal blood flow
Characterized by severe pain in the back, chest, abdomen, extremities, and head
Highly disruptive to life
Most common reasons for individuals to seek health care

19. Medical Complications
kidney damage and
loss of body water in urine
painful erections in men (priapism)
blood blockage in the spleen or liver (sequestration)
eye damage
low red blood cell counts (anemia)
delayed growth
pain episodes
strokes
increased infections
leg ulcers
bone damage
yellow eyes or jaundice
early gallstones
lung blockage

20. Serious Complications
Strokes
Up to 15% of children may have overt or silent strokes during childhood
Chronic transfusion therapy reduces the recurrence rate of overt stroke which may approach 75% without intervention
Bone disease
Early risk is primarily from osteomyelitis
Infectious usually painful inflammatory disease of bone often of bacterial origin and may result in bone tissue death
Avascular necrosis of the femur and humerus
Death of bone tissue due to disrupted blood supply
Marked by severe pain in the affected region and by weakened bone that may flatten and collapse

21. Danger Signs of a Crisis
Any sudden weakness or
loss of feeling
Pain that will not go away
with home treatment
Priapism (painful erection
that will not go down)
Sudden vision change
Fever
Chest pain
Shortness of Breath
Increasing tiredness
Abdominal swelling
Unusual headache
SEEK URGENT HOSPITAL TREATMENT IF IN CRISIS

22. Crises During a crisis severe pain in the fingers, toes,
arms, joints,legs, back, abdomen, and bones.
Decrease in oxygen to the chest and lungs
May lead to acute chest syndrome
Damage to the lungs
Severe pain and fever
Lungs' airways narrow, further reducing O2
Leads to an increased risk of potentially
fatal infections

23. Triggers of Pain Infections
Thirst and dehydration caused by not drinking enough even if thirst is not felt
Over-exertion
Over-excitement
Cold weather and cold drinks and swimming
Bangs, bumps, bruises and strains
Stress triggers pain in adults, but does not seem to do so in children.

24. Daily Preventative Measures
Taking the folic acid (folate) daily to help make new red cells
Daily penicillin until age six to prevent serious infection
Drinking plenty of water daily (8-10 glasses for adults)
Avoiding too hot or too cold temperatures
Avoiding over exertion and stress
Getting plenty of rest
Getting regular check-ups from knowledgeable health care providers

25. Developing Treatments
Bone marrow transplantation
Shown to provide a cure for severely affected children with sickle cell disease
Only about 18 percent of children with sickle cell anemia are likely to have a matched sibling.

26. The Ultimate Cure? Gene Therapy
Correcting the “defective gene” and inserting it into the bone marrow
Turning off the defective gene and simultaneously reactivating another gene that turns on production of fetal hemoglobin.
No real cure for Sickle Cell Anemia at this time.
“In the past 30 years, the life expectancy of people with sickle cell anemia has increased. Many patients with sickle cell anemia now live into their mid-forties and beyond.”

27. Websites http://www.sicklecellsociety.org/ : Another Great Site
information, Counselling and Caring for those with Sickle Cell Disorders and their families: UK based
Sickle Cell Disease Association of America
The Human Genome Project Sickle Cell Education Site at
American Sickle Cell Anemia Association
ASCAA was founded in 1971 and is the oldest sickle cell research, education, and social services organization in the United States.
Planet Sickle Cell Society (UK based)
-Youth support, Poetry, Pen-Pals, Information, Message Board
The STARBRIGHT Foundation is dedicated to the development of projects that empower seriousl ill children to combat the medical and emotional challenges they face on a daily basis.
Coloring Books on Sickle Cell from Emory: