1. Sickle Cell Anemia Most common genetic disease in US
high incidence in African-Americans
affects red blood cells
potentially lethal

2. 10 µm 10 µm Normal red blood cells are full of individual hemoglobin
Fig. 5-22c
10 µm
10 µm
Normal red blood
cells are full of
individual
hemoglobin
molecules, each
carrying oxygen.
Fibers of abnormal
hemoglobin deform
red blood cell into
sickle shape.

3. Symptoms Anemia Hypoxia (low oxygen) & capillary damage Delayed growth
Link to HHMI sickle cell link
Anemia
jaundice, fatigue, paleness, shortness of breath
Hypoxia (low oxygen) & capillary damage
severe pain in organs & joints
retinal damage (blindness)
Delayed growth
delayed puberty, stunted growth
Infections
more susceptible
depressed immune
death from bacterial infections
Stroke
blocked small blood vessels in brain
primarily in children

4. Genetics Sickle cell mutation Recessive allele Hb A Hb S HbAA HbAS
changes 6th amino acid of  hemoglobin chain
normal glutamic acid  valine
Recessive allele
heterozygote
Hb AS, normal, but carrier
homozygote recessive
Hb SS, sickle cell disease
2 sickle cell carriers mate…
each child has 1/4 chance of having the disease
Hb A
Hb S
HbAA
HbAS
Hb A
Hb S
HbAS
HbSS

5. The Malaria Connection
Sickle cell disease is surprisingly common for a potentially lethal genetic disease
Heterozygote advantage
heterozygotes are tolerant of malaria infection & symptoms of sickle cell disease are not as severe

6. Malaria

7. Prevalence of Malaria
Prevalence of Sickle Cell Anemia

9. Conformational change of hemoglobin when O2 binds

10. Sickle Cell is the result of a single point mutation in DNA

12. Compare the properties (size, shape, charge) of Valine vs
Compare the properties (size, shape, charge) of Valine vs. Glutamic Acid.
Glutamic Acid
Valine

13. mutant hemoglobin (Hb S)
Sickle cell hemoglobin
mutant hemoglobin (Hb S)

14. HYDROPHOBIC “STICKY PATCHES” CAUSE MUTATED BETA SUBUNITS FROM DIFFERENT HEMOGLOBINS TO STICK TOGETHER

16. Fig. 5-22 Normal hemoglobin Sickle-cell hemoglobin Primary structure
Val
His
Leu
Thr
Pro
Glu
Glu
Val
His
Leu
Thr
Pro
Val
Glu 1 2 3 4 5 6 7 1 2 3 4 5 6 7
Exposed
hydrophobic
region
Secondary
and tertiary
structures
Secondary
and tertiary
structures
 subunit
 subunit    
Quaternary
structure
Normal
hemoglobin
(top view)
Quaternary
structure
Sickle-cell
hemoglobin    
Function
Molecules do
not associate
with one
another; each
carries oxygen.
Function
Molecules
interact with
one another and
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.
10 µm
10 µm
Red blood
cell shape
Normal red blood
cells are full of
individual
hemoglobin
moledules, each
carrying oxygen.
Red blood
cell shape
Fibers of abnormal
hemoglobin deform
red blood cell into
sickle shape.

17. Link to Sickle Cell Animation