______ _____________ _______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.