November 7, 2013

1. 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? November 7, 2013

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

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 • 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 • 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 tissuedeath • 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 inchildren.

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 http://www.sicklecelldisease.org/: Sickle Cell Disease Association of America The Human Genome Project Sickle Cell Education Site at http://www.massinteraction.org/html/genome/ http://www.ascaa.org/ 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. http://www.ncd.gov/ http://www.painfoundation.org/ http://www.sicklecellsociety.org/sicklescene/pshomf.htm Planet Sickle Cell Society (UK based) -Youth support, Poetry, Pen-Pals, Information, Message Board http://www.starbright.org/ 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: http://www.emory.edu/PEDS/SICKLE/bbc/index.htm http://www.emory.edu/PEDS/SICKLE/chelate/index.htm