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Genetic Diseases
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In this scenario, both parents are
heterozygous for a particular allele
A = dominant allele
a=recessive allele
If these two individuals were to
produce offspring, the possibility of
their child having a certain genotype is
as such:
AA, homozygous dominant 1:4
Aa, heterozygous 1:2
Aa, homozygous recessive 1:4
Basic Punnett Square
If the disease we were concerned
about was expressed through a
dominant allele, the offspring would
have a 3:4 chance of inheriting the
disease.
affected
affected
affected
unaffected
unaffected
unaffected
unaffected
affected
If the disease we were concerned
about was expressed through a
recessive allele, the offspring would
have a 1:4 chance of inheriting the
disease.
Aa offspring are “carriers”. Although they may not express the phenotype associated
with a recessive disease, they carry an allele for it, and thus can pass it on to their
offspring.
Why do alleles cause these
disorders?
Mutations arise in genes that are
passed down to through the alleles
to the offspring.
Tay Sachs Disease
 An autosomal recessive disorder
 Causes a buildup of gangliosides in
the brain, resulting in mental
retardation and eventually death
 Caused by a mutation of the HEXA
gene on chromosome 15
 Time of onset of disease is crucial
 If onset is during infancy, disease is
severe and mortality is high
 If onset is during juvenile or adult
years, mortality not as high
The Difference in Years
Juvenile-onset
Infantile-onset
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Neurological
deterioration between 36 months of age
Motor development
plateaus/regresses at 810 months
Loss of vision begins at 1
year of age (cherry red
spot starts)
Seizures begin at end of
age 1
Loss of voluntary
movement by age 2
Death by 2-4 years
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Manifests at 2-4 years
of age
Begins with
neurological
deterioration
By age 10, individuals
with juvenile Tay Sachs
will experience seizures
By 10-15 years of age,
most individuals will
enter a vegetative state
Adult-onset
•Great variability in clinical
symptoms
•Less than half of
individuals with adult Tay
Sachs have psychiatric
manifestations
•Vision is rarely affected
The Cherry Red Spot
Individuals with Tay Sachs disease are often identified by the “cherry red spot” seen when
they receive an eye examination. The red circle seen towards the center of the eye is
actually normal retina, while the white surrounding cells are the ones affected by abnormal
storage of gangliosides in the retinal neurons.
Achondroplasia (Dwarfism)
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Achondroplasia is the most common
cause of dwarfism in humans
Autosomal dominant disorder
Mutations that are linked to growth
factors are the primary causes of
dwarfism
In the case of achondroplasia, the
mutation lies in FGFR3
–
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“gain of function” mutation : FGFR3
becomes overactive
Affects all races
Radiographs of two fetus at 34 weeks. The two pictures on the left are from a normal
fetus, and the two on the right from a fetus with achondroplasia.
Achondroplasia is a Dominant Disorder
I
II
III
IV
Dominantly inherited traits are easily identified on a pedigree because they are
expressed every generation.
Sickle Cell Anemia
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An autosomal recessive disorder
The sickle cell allele is known as Hs.
When oxygen content is low, the
diseased hemoglobin deforms into a
sickle shape.
The constant change between normal
oxygenated red blood cells and
deoxygenated sickle cells causes
some cells to become permanently
sickled.
It is most common individuals of
African-American descent
The mutation is caused by the substitution of a single amino acid in HBB.
Symptoms of sickle cell
anemia
•Anemia
•Failure to thrive
•Repeated infections
•Dactylitis (painful swelling of hands
and feet)
•Stroke
•Leg ulcers (shown on the left)
•Visual loss
•Bone aseptic necrosis
•Splenomegaly
The sickle cell allele provides unique
traits that benefits its carriers
Although Sickle Cell Anemia is overall a
recessive disorder, the alleles express
incomplete dominance at the
molecular level. Those who are
carriers of the disease express certain
traits sickle cell anemia. Their cells do
produce some fibrous polymers, but
not enough to cause harm to the
individual. The majority of carriers
express no symptoms of sickle cell and
are overall clinically silent. Individuals
heterozygous for sickle cell are also
resistant to malaria. This is a survival
advantage in areas where malaria is a
major concern, and has helped the
disorder prevail.
Geographic overlap of
sickle cell anemia with
malaria is most evident in
Africa
Amniocentesis
Chorionic Villus Sampling
10-20 ml of amniotic fluid is taken from
the amniotic cavity with a needle for
various tests. Ultrasound is usually used
during the procedure to ensure the
safety of the fetus. This procedure can
be performed at 14-16 weeks after
conception, and takes several weeks to
complete.
A small amount of fetal tissue is taken
from the placenta via spinal needle or
cannula. Ultrasound is used in
conjunction with this test to ensure the
safety of the fetus. Results are obtained
within 24 hours of the procedure
because the cells obtained from the
placenta divide at a rapid rate. This test
may be performed 8-10 weeks after
conception.
Ultrasound
•Sound waves are used to produce
the image of the fetus.
Fetoscopy
•A tube containing fiber optics
and a viewing scope is
inserted into the uterus to
view the fetus for anatomical
abnormalities and/or
deformities.