Q1. Bill has come to you for genetic counseling. He is concerned that he and his sister (Alice) are at risk for Huntington disease. Bill and Aliceare too young to show symptoms. Their grandmother, (Mary) had Huntington disease. Her three children, Shirley, Tom, and Ed so far show no symptoms. Shirley is the oldest (45 years old) and is Bill and Alice's mother. A study by Adams (American Journal of Human Genetics 43;695 - 704, 1988) indicates that 68% of individuals heterozygous for the Huntington allele show symptoms by age 45.  

a. Draw a pedigree of this family.

b. What is the probability that Bill is heterozygous for Huntington disease?

c. What test(s) would you recommend for Bill? Explain why you recommend this test, what information it can give, and how this information can answer their question.

d. If you determine that Bill is heterozygous for the Huntington disease allele, what is the probability that Alice is also heterozygous? 

Q2. A patient in your clinic has a tumor and two hypotheses have been suggested for the origin of the cancer. One is that the tumor cells are infected with a transforming retrovirus whose oncogene is a modified human EGF receptor gene. The second is that the tumor cells are homozygous for a loss of function mutation of a gene whose product is a kinase essential for maintaining the G1 => S mitotic checkpoint. 

a. Design a test to distinguish between these two hypotheses.

b. What results would you expect from your test if the cancer has been caused by the retrovirus?

c. Explain you chose this test, and how the results support the retroviral hypothesis to the patient, who is not a scientist.

Q3. A couple, Ricky and Rachel have come to you for genetic counseling.  They are expecting a child and are concerned that it may have cystic fibrosis. Rachel's father had a sister with cystic fibrosis. Rachel's parents and her three older brothers have no signs of disease. Rachel and all her family are white.   Ricky, who is younger than Rachel, has two younger brothers and a sister (the youngest sibling). He and all his family are Hispanic and no one in his family has cystic fibrosis.  Ricky was tested for a cystic fibrosis allele using the ACMG panel test and the result was negative.

a. Draw a pedigree of these families

b. What is the probability that their child will have cystic fibrosis?

c. Explain to the couple, who are not scientists, how you derived that probability.

d. The couple asks if there is anything else that they can do to learn more about their child's chances of having cystic fibrosis.  What would you recommend?

Q4. A HIV positive patient of European ancestry has been referred to you for treatment.  A standard treatment is a cocktail of retroviral drugs including abacavir. Before prescribing this you review the patient's records and see that one of her uncles had a lethal reaction to abacavir treatment.

a. What test or tests would you do on the patient before starting her on abacavir?

b. What results of your test would cause you to not make this prescription? 

c. Explain to the patient, who is not a scientist, what tests you want to do and why you want to do these tests.

Q5. A couple (IV2, IV3) are concerned their first child might have holoprosencephaly. Two members of their family (III1 and III6) have it.  Individuals III3 and III5 are from another population in which this disorder does not occur.  There are two hypotheses about holoprosencephaly in this family.  (1) There is a recessive mutant allele of the TGIF gene with an altered enhancer/promoter region that represses the transcription of SHH in the developing embryonic brain. (2) There is a recessive mutant allele of SHH with an altered enhancer/promoter region that decreases the level of transcription of SHH in the developing embryonic brain.

a. What is the probability that the first child of IV2 and IV3 will have holoprosencephaly?

b. What test could you do to determine which hypothesis is correct?

c. What results would you expect from your test if hypothesis 1 is correct?

Q6. You are a genetic counselor reviewing yourself and your family. Choose one trait or characteristic that you have that you believe is inherited.

a. Describe that trait.

b. Prepare a pedigree of your family showing the inheritance of that trait.

c. Make a hypothesis describing the characteristics of the allele causing that trait.

You may include photographs to show the trait / phenotype.