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______ _____________ _______Genetic DiseasesGenetic Diseases
Basic Punnett Square
In this scenario, both parents are heterozygous for a particular allele
A = dominant allelea=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 1:4Aa, heterozygous 1:2Aa, homozygous recessive 1:4
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
Infantile-onset• Neurological
deterioration between 3-6 months of age
• Motor development plateaus/regresses at 8-10 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
Adult-onset• 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
Juvenile-onset•Great variability in clinical symptoms•Less than half of individuals with adult Tay Sachs have psychiatric manifestations •Vision is rarely affected
The Difference in Years
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)• 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– “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
Dominantly inherited traits are easily identified on a pedigree because they are expressed every generation.
I
II
III
IV
Sickle Cell Anemia
• 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
AmniocentesisA 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.
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.
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.