Second examination articles and questions

Consugar, M. B., S. A. Anderson, S. Rossetti, V. S. Pankratz, C. J. Ward et al., 2005 Haplotype analysis improves molecular diagnostics of autosomal recessive polycystic kidney disease. Am. J. Kidney Dis. 45(1): 77–87.
    a. What is an exon?
    b. How is the ARPD gene different from almost any gene in bacteria?
    c. What is the meaning of:
        1. Allelic heterogeneity
        2. Missense mutation
        3. Polymorphism
    d. Give an example of a simple sequence repeat marker:
    e. How would screening for a larger DNA deletion help detect unknown consanguinity?
    f. How would recombination lead to divergence from an ancestral genotype (draw a diagram as an example)?
Kirman, C. R., L. M. Sweeney, M. J. Teta, R. L. Sielken, C. Valdez-Flores et al., 2004 Addressing nonlinearity in the exposure- response relationship for a genotoxic carcinogen: cancer potency estimates for ethylene oxide. Risk Anal. 24(5): 1165–1183.
    a. Draw a dose response curve where risk is proportional to the square of the dose.
    b. Why might it be necessary to extrapolate to low dose?
    c. Draw curves showing risk linearly proportional to dose (1) and with no risk at low dose (2).
    d. What is the dose at which an effect is first seen called?
    e. What might be the practical implications for the manufacturers and/or users of ethylene oxide of the different hypotheses?
Xu, L., K. Tsuji, H. Mostowski, M. Otsu, F. Candotti et al., 2004 A convenient method for positive selection of retroviral producing cells generating vectors devoid of selectable markers. J. Virol. Methods 118(1): 61–67.
    a. What is a retroviral vector?
    b. What is a dominant selectable marker gene and why is it important for cloning?
    c. Why is it often necessary to associate a therapeutic gene with such a marker gene?
    d. What does the abstract suggest is the problem with this approach?
    e. How did the investigators attempt to solve the problem?
Eisensmith, R. C., D. R. Martinez, A. I. Kuzmin, A. A. Goltsov, A. Brown et al., 1996 Molecular basis of phenylketonuria and a correlation between genotype and phenotype in a heterogeneous southeastern US population. Pediatrics 97(4): 512–516.
    a. Explain briefly how the direct sequence analysis was done (i.e., indicate briefly the theoretical basis of the method).
    b. What might be the basis of different serum phenylalanine levels or phenylalanine tolerance in the different patients?
    c. Why might the different mutations lead to somewhat different clinical outcomes?
    d. Why was it necessary to use non-related patients in the study?
el-Hazmi, M. A., A. S. Warsy, A. R. al-Swailem, A. M. al-Swailem and H. M. Bahakim, 1996 Sickle cell gene in the population of Saudi Arabia. Hemoglobin 20(3): 187–198.
    a. What would the electrophoretic patterns look like in the heterozygous and homozygous states (draw a diagram on the back of this page)?
    b. What was the overall population in Hardy-Weinberg equilibrium? How do you (and the authors) know?
    c. Given the gene frequency stated, what would be the expected frequency of sickle-cell anemia?
    d. Why might one expect a close connection between HbS gene frequency and malaria?