First examination articles and questions

Simerly, C., C. Navara, S. H. Hyun, B. C. Lee, S. K. Kang et al., 2004 Embryogenesis and blastocyst development after somatic cell nuclear transfer in nonhuman primates: overcoming defects caused by meiotic spindle extraction. Dev. Biol. 276(2): 237–252.
    a. What is the problem that the use of embryonic stem (ES) cells might solve? Why should ES cells be of particular use?
    b. How (in outline) would one proceed to derive a blastocyst by somatic cell nuclear transfer? What is a blastocyst?
    c. The abstract speaks of enucleation just prior to metaphase-II arrest. Explain what metaphase-II arrest is and where and when it happens.
    d. What evidence does the abstract give related to the possibility of actually deriving cloned monkeys by somatic cell nuclear transfer?
    e. What is an aneuploid preimplantation embryo and why might a centrosome deficiency result in the production of such embryos?
    f. How might these results be used to argue that ES cell research is fundamentally different from attempts to clone primates? (Alternatively, or if the question offends you, argue that these results show that ES cell research is not fundamentally different from attempts to clone primates.)
Melo, K. F., B. B. Mendonca, A. E. Billerbeck, E. M. Costa M. Inacio et al., 2003 Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: five novel mutations in the androgen receptor gene. J. Clin. Endocrinol. Metab. 88(7): 3241–3250.
    a. According to the abstract, is AIS an “all or none” condition or are there varying degrees of severity?
    b. The abstract suggests that the family history was suggestive of X-linked inheritance. Draw the type of pedigree that might have been seen and that would suggest X-linked inheritance.
    c. What does the abstract suggest is the cause of AIS and what evidence does it give to support this idea?
    d. Although the abstract does not specify, what might be the reason for the distinction between CAIS and PAIS?
    e. Comment on the following sentence in the abstract: “All subjects with PAIS maintained at postpubertal age the gender identity and social sex that was assigned to them in infancy, in contrast to other forms of pseudohermaphroditism.”
Shaffer, L. G., C. K. Jackson-Cook, B. A. Stasiowski, J. E. Spence and J. A. Brown, 1992 Parental origin determination in thirty de novo Robertsonian translocations. Am. J. Med. Genet. 43(6): 957–963.
(rob in a chromosome designation indicates a Robertsonian translocation)
    a. What would you expect the phenotype of the balanced Robertsonian translocation individuals to be?
    b. What chromosomes were involved in the translocations?
    c. What would be the phenotype of all rob(14q21q) ascertained through unbalanced probands (20/20)?
    d. What was unexpected about the origin and composition of these unbalanced probands?
    e. Draw a diagram indicating the authors' explanation for the homozygosity of the chromosome 21 loci (considering only the maternal-derived loci).
Ottman, R., M. R. Winawer, S. Kalachikov, C. Barker-Cummings, T. C. Gilliam et al., 2004 LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 62(7): 1120–1126.
    a. Draw a pedigree of a family with a member showing ADPEAF. Make the pedigree extensive enough to eliminate alternative interpretations.
    b. What is meant by penetrance?
    c. How would low penetrance show up in the pedigree you have drawn?
    d. Just from the abstract, and notwithstanding any conclusion the authors reach, what question(s) might one ask about the relation of the mutations in LGI1 and the epilepsy?