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?

SICKLE CELL DISORDER A mutation that is good and bad Video

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.

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.

Sickle Cell Gene Severe Malaria

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.

History

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.

Who is at risk?

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

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)

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

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

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

Genetics 2 copies of the gene

for Hb (each parent)

HbS –Recessive S=Sickle A=Normal

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 exceptions1. Pain when Less Oxygen than usual (scuba

diving, activities at high altitude (12,000ft), under general anaesthesia)

2. Minute kidney problems

1. Sickle Cell Anemia Sickle haemoglobin (HbS) + Sickle haemoglobin (HbS) Most Severe – No HbA

2. Hemoglobin S-C disease Sickle haemoglobin (HbS) + (HbC)

3. Hemoglobin S-Beta thalassemia Beta thalassaemia gene reduces the amount

of HbA that can be madeSickle haemoglobin (HbS) + reduced HbAMilder form of Sickle Cell Disorder than sickle

cell anemia

Three common types of Sickle Cell Disorders

Screening1. Haemoglobin Electrophoresis

Simple Blood test Routine screening in high risk groups

• During pregnancy• Before anaesthesia

2. 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

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

Serious Complications: PAINRecurrent 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

Medical Complications

1. pain episodes 2. strokes 3. increased

infections4. leg ulcers 5. bone damage 6. yellow eyes or

jaundice 7. early gallstones 8. lung blockage

9. kidney damage and loss of body water in urine 10.painful erections in men

(priapism) 11.blood blockage in the

spleen or liver (sequestration)

12.eye damage 13.low red blood cell counts

(anemia) 14.delayed growth

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

Serious Complications

1. Fever 2. Chest pain 3. Shortness of

Breath 4. Increasing

tiredness 5. Abdominal

swelling 6. Unusual headache

Danger Signs of a Crisis

7. Any sudden weakness orloss of feeling

8. Pain that will not go away with home treatment

9. Priapism (painful erection that will not go down)

10.Sudden vision changeSEEK URGENT HOSPITAL TREATMENT IF IN CRISIS

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

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.

Triggers of Pain

1. Taking the folic acid (folate) daily to help make new red cells

2. Daily penicillin until age six to prevent serious infection

3. Drinking plenty of water daily (8-10 glasses for adults)

4. Avoiding too hot or too cold temperatures 5. Avoiding over exertion and stress 6. Getting plenty of rest 7. Getting regular check-ups from knowledgeable

health care providers

Daily Preventative Measures

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.

Developing Treatments

The Ultimate Cure? Gene Therapy

1. Correcting the “defective gene” and inserting it into the bone marrow

2. 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.”

Websiteshttp://www.sicklecellsociety.org/ : Another Great Siteinformation, 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 AssociationASCAA 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.htmhttp://www.emory.edu/PEDS/SICKLE/chelate/index.htm