Among the affected individuals, two were heterozygotes for FVL and one was homozygous for FVL. Set up a 3 × 2 table for the association of the homozygous FVL genotype, the heterozygous FVL genotype, and the wild-type genotype for iCVT.
What is the relative risk for iCVT in a FVL heterozygote versus the wild-type genotype? What is the risk in a FVL homozygote versus wild-type? What is the sensitivity of testing positive for either one or two FVL alleles for iCVT? Finally, what is the positive predictive value of being homozygous for FVL? heterozygous?

2. In a population sample of 100,000 European women taking oral contraceptives, deep venous thrombosis (DVT) of the lower extremities occurred in 100, consistent with an expected rate of 1 per 1,000. Assuming an allele frequency of 2.5% for factor V Leiden (FVL), how many homozygotes and how many heterozygotes for FVL would you expect in this sample of 100,000 women, assuming Hardy-Weinberg equilibrium?
Among the affected individuals, 58 were heterozygotes for FVL and three were homozygous for FVL. Set up a 3 × 2 table for the association of the homozygous FVL genotype, the heterozygous FVL genotype, and the wild-type genotype for DVT of the lower extremity.
What is the relative risk for DVT in a FVL heterozygote using oral contraceptives versus women with the wild-type genotype taking oral contraceptives? What is the risk in a FVL homozygote versus wild-type? What is the sensitivity of testing positive for either one or two FVL alleles for DVT while taking oral contraceptives? Finally, what is the positive predictive value for DVT of being homozygous for FVL while taking oral contraceptives? Heterozygous?

3. What steps should be taken when a phenylketonuria (PKU) screening test comes back positive?

4. Newborn screening for sickle cell disease can be performed by hemoglobin electrophoresis, which separates hemoglobin A and S, thereby identifying individuals who are heterozygotes as well as those who are homozygotes for the sickle cell mutation. What potential benefits might accrue from such testing? What harms?

5. Toxic epidermal necrolysis (TEN) and the Stevens-Johnson syndrome (SJS) are two related, life-threatening skin reactions that occur in approximately 1 per 100,000 individuals in China, most commonly as a result of exposure to the antiepileptic drug carbamazepine. These conditions carry a significant mortality rate of 30% to 35% (TEN) and 5% to 15% (SJS). It was observed that individuals who suffered this severe immunological reaction carried a particular major histocompatibility complex class 1 allele, HLA-B*1502, as do 8.6% of the Chinese population. In a retrospective cohort study of 145 patients who received carbamazepine therapy, 44 developed either TEN or SJS. Of these, all 44 carried the HLA-B*1502 allele, whereas only three of the patients who received the drug without incident were HLA-B*1502 positive. What is the sensitivity, specificity, and positive predictive value of this allele for TEN or SJS in patients receiving carbamazepine?

6. In 1997, a young female college student died suddenly of cardiac arrhythmia after being startled by a fire alarm in her college dormitory in the middle of the night. She had recently been prescribed an oral antihistamine, terfenadine, for hay fever by a physician at the school. Her parents reported that she would take her medications every morning with breakfast, which consisted of grapefruit juice, toast, and caffeinated coffee. Her only other medication was oral itraconazole, which she was given by a dermatologist in her home town to treat a stubborn toenail fungus that she considered unsightly. Terfenadine was removed from the U.S. market in 1998.
Do a literature search on sudden cardiac death associated with terfenadine, relating possibly genetic and environmental factors that might have interacted to cause this young woman’s death.

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