Sickle Cell Anemia

Molecular Genetics Lab

what is sickle cell anemia

an inherited red blood cell disorder

what shape are normal red blood cells

round

what is the function of normal red blood cells

to transport oxygen through the body

what shape do sickle cells have

sickle or cresent shape

why are sickle cells harmful

they become hard and sticky, clog blood vessels, and break apart easily

what can sickling cause

pain, tissue damage, and anemia

what protein is altered in sickle cell disease

hemoglobin

what causes the abnormal cell shape

change in the structure of hemoglobin

how many amino acid changes cause sickle cell disease

one amino acid change

what happens to sickle hemoglobin molecules

they aggregate (stick together)

what is the function of hemoglobin

carry oxygen

where does hemoglobin pick up oxygen

the lungs

where does hemoglobin deliver oxygen

to body tissues

what molecule does deoxyhemoglobin carry back to the lungs

carbon dioxide

in which gene does the sickle mutation occur

the beta globin gene

which codon contains the mutation

the 6th codon of the beta globin gene

what is the normal DNA codon

GAG

what is the sickle cell DNA codon

GTG

which amino acid does GAG encode

glutamic acid

which amino acid does GTG encode

valine

what amino acid substitution cause sickle cell disease

glutamic acid → valine

what charge does glutamic acid have

negative

is glutamic acid hydrophilic or hydrophobic

hydrophilic (charged)

is valine polar or nonpolar

nonpolar

is valine hydrophilic or hydrophobic

hydrophobic

why does replacing glutamic acid with valine matter

it creates a hydrophobic patch that promotes hemoglobin aggregation

how many subunits does hemoglobin contain

4

how many alpha subunits are present

2

how many beta subunits are present

2

how many heme groups are present

4

what binds oxygen in hemoglobin

heme groups

what amino acid change is present in Hbs

Glu → Val

what happens to Hbs molecules

they stick together and aggregate

why do red blood cells become sickle shaped

aggregated Hbs distorts the red blood cell

which hemoglobin molecules aggregates HbA or HbS

HbS

is the sickle allele considered deleterious

yes

what deleterious mean

harmful and associated with decreased fitness

why has natural selection not eliminated HbS

HbS provides protection against malaria

what is heterozygous advantage

heterozygotes have increased fitness compared to either homozygous

what laboratory test is commonly used to diagnose sickle cell disease

hemoglobin electrophoresis

what does electrophoresis separate

different forms of hemoglobin

what are four inheritance patterns emphasized in lab

autosomal recessive

autosomal dominant

x linked dominant

x linked recessive

what inheritance pattern does sickle cell disease follow

autosomal recessive

do autosomal recessive traits skip generations

yes

do autosomal recessive traits affect males and females equally

yes

are autosomal recessive traits usually common or rare in pedigrees

rare

are autosomal dominant traits usually found in every generation

yes

how many daughters inherit an x linked trait from an affected father

all daughters

are males and females equally likely to be affected in x linked dominant pedigrees

yes

do affected fathers pass an x linked recessive trait to sons

no

which sex is more commonly affected in x linked recessive traits

males

do x linked recessive traits often skip generations

yes