Bio A – Mendelian Genetics
Human Genetic Diseases
I.
Achondroplasia (Dwarfism)
Achondroplasia is a disorder of bone growth. It is the most common form of disproportionate short stature. It
occurs in one in every 15,000 to one in 40,000 live births. Achondroplasia is caused by a gene alteration
(mutation) in the FGFR3 gene. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is
involved in converting cartilage to bone. FGFR3 is the only gene known to be associated with achondroplasia. All
people who have only a single copy of the normal FGFR3 gene and a single copy of the FGFR3 gene mutation have
achondroplasia.
Most people who have achondroplasia have average-size parents. In this situation, the FGFR3 gene mutation
occurs in one parent's egg or sperm cell before conception. Other people with achondroplasia inherit the condition
from a parent who has achondroplasia
1. Reread the underlined sentence. Is achondroplasia a dominant disease or a recessive disease?
2. The TV show “Little people, Big world” is about a family some of which have achondroplasia. The mother and
father have the disease. They have 4 children: three sons and one daughter. One of the three sons has
achondroplasia. The other three children are normal height.
a. Draw a mini pedigree for this family using all the correct symbols.
b. Write the genotypes above each family member. If there are multiple possibilities, write both
possibilities.
3. Assuming the daughter marries a man without the disease, can any of their children have the disease? Explain
using a punnett square.
Bio A – Mendelian Genetics
II.
Cystic fibrosis (CF) is the most common, fatal genetic disease in the United States. About 30,000 people in
the United States have the disease. CF causes the body to produce thick, sticky mucus that clogs the
lungs, leads to infection, and blocks the pancreas, which stops digestive enzymes from reaching the
intestine where they are required in order to digest food.
Mutations in a single gene - the Cystic Fibrosis Transmembrane Regulator (CFTR) gene - causes CF. When
this gene is working normally it regulates a person’s salt balance. When it is mutated, a salt imbalance
creates the sticky mucus. Often parents diagnose their babies when they kiss their foreheads and the
babies taste salty!! Luckily the disease is recessive, so parents who have a family history of CF often get
tested before having children.
A woman who is heterozygous for the CF mutation marries a man with CF. What percent chance do they
have of having a healthy child? Show your punnett square to support your answer.
What vocabulary term can be used for the healthy children who have one copy of the disease allele to
indicate that they can pass the gene on to their offspring?
Bio A – Mendelian Genetics
III. Hemophilia is a recessive bleeding disorder that slows down the blood clotting process. People who have
hemophilia often have longer bleeding after an injury or surgery. People who have severe hemophilia have
spontaneous bleeding into the joints and muscles. Hemophilia occurs more commonly in males than in females.
Hemophilia A is the most common type of this condition. One in 5,000 to 10,000 males worldwide have hemophilia A.
Hemophilia B is less common, and it affects 1 in 20,000 to 34,500 males worldwide.
1.
Reread the underlined sentence. What does this suggest about the Hemophilia ?
2. A woman who is a carrier for hemophilia marries a normal male. What is the PHENOTYPIC ratio of the
children (include sex AND whether or not they have the disease)
3. A homozygous normal female marries a hemophilic male. Should they be concerned about their children
having the disease? If so what percent of their children are at risk?
Bio A – Mendelian Genetics
IV. Tay Sachs Disease
Tay-Sachs disease (TSD) is a fatal genetic disorder, most commonly occurring in children, that results in progressive
destruction of the nervous system. Tay-Sachs is caused by the absence of a vital enzyme called Hex-A. Without HexA, a fatty substance accumulates abnormally in cells, especially in the nerve cells of the brain. This ongoing
accumulation causes progressive damage to the cells.
In children, the destructive process begins in the fetus early in pregnancy. However, a baby with Tay-Sachs disease
appears normal until about six months of age when its development slows. By about two years of age, most children
experience recurrent seizures and diminishing mental function. The infant gradually regresses, and is eventually
unable to crawl, turn over, sit or reach out. Eventually, the child becomes blind, cognitively impaired, paralyzed and
non-responsive. By the time a child with Tay-Sachs is three or four years old, the nervous system is so badly affected
that death usually results by age five.
Carriers have a 50 percent chance of passing on the defective gene to their children. A child who inherits one inactive
gene is a Tay-Sachs carrier like the parent. If both parents are carriers and their child inherits the defective Hex-A
gene from each of them, the child will have Tay-Sachs disease. When both parents are carriers of the defective TaySachs gene, each child has a 25 percent chance of having Tay-Sachs disease and a 50 percent chance of being a
carrier
1.
The LAST paragraph is key for identifying the inheritance pattern of Tay Sachs. Is Tay Sachs dominant or
recessive? Describe TWO CLUES given to you in the last paragraph that helped you determine.
2.
Mother and Father both know they have a family history of Tay Sachs disease. They go to a genetic counselor
and find out that they are both heterozygous for the disease. What percent chance do they have that their child
will be NORMAL? Show your punnett square to support your answer.
Bio A – Mendelian Genetics
V. Sickle Cell Disease
Sickle cell disease is the most common inherited blood disorder in the United States. Approximately 80,000 Americans
have the disease. In the United States, sickle cell disease is most prevalent among African Americans. Sickle cell
disease is caused by a mutation in the hemoglobin which transports oxygen from the lungs to other parts of the body.
Red blood cells with normal hemoglobin are smooth and round and glide through blood vessels without problem.
In people with sickle cell disease, abnormal hemoglobin molecules stick to one another and change the shape of the
red blood cell from round to pointy. Their shape causes these red blood cells to pile up, causing blockages and
damaging vital organs and tissue.
Now… here is the tricky part. A person who is heterozygous for the sickle cell gene produces normal AND sickle
shaped red blood cells, BUT the presence of normal cells is enough to keep the individual from suffering from sickle
cell anemia.
ALSO, since sickle shaped red blood cells cannot be infected by the parasite that causes malaria, the heterozygous
people have an advantage: they don’t suffer from sickle cell anemia AND they are resistant to malaria.
- Look at the underlined sentence. Does this gene display complete dominance, co-dominance or incomplete
dominance? How do you know?
- If you live in a hot and humid climate where the parasite for malaria is very common, what genotype would you
want to have and why?
- A person with sickle cell anemia marries a carrier for the disease. Draw the punnett squares and then answer the
following questions.
-
What chance do they have of having a homozygous normal child?
-
What chance do they have of having a child that is resistant to malaria but WITHOUT sickle
cell?
-
What chance do they have of having a child that has sickle cell anemia?