Genetics 371B Practice problems--Autumn 2000 week 7

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1. A tumor the size of a marble, about 1 cubic centimeter in volume, may contain 109 cells. How many cell generations (starting from a single cell) are required to produce this tumor? How many cell divisions were involved? (This one is just to get you thinking about the difference between cell divisions and cell generations. The first part requires a little bit of algebra. The answers are provided; explain how to get there.)

Answer:

# of generations = 29.9 (rounded up to 30)

# of cell divisions = 999,999,999.

2. Some uterine tumors consist of as many as 1011 cells. In women heterozygous for a particular X-linked gene, researchers have discovered that every cell of such a tumor has the same active X-linked allele. Explain this observation in terms of the Lyon hypothesis.

3. Shown below is the transcription activation pathway for Gene X, needed for entry into S phase. Binding of growth factor to the receptor (Protein 1) causes the receptor to phosphorylate Protein 2. As a result, Protein 2 releases Protein 3, which is then free to enter the nucleus and activate transcription of Gene X.

(a)

 Proteins 1 through 3 are encoded by Genes 1-3. For each gene:

(i) is a mutation (any random mutation) more likely to result in an allele that promotes cancer, or in a non-cancer allele? Explain.
(ii)

what kind of mutation in that gene would result in an allele that is more likely to promote progression toward cancer -- a gain-of-function mutation or a loss-of-function mutation.

(iii) Would the cancer-promoting allele be dominant or recessive? Assume that each gene product is normally present in excess.

(b) Suppose that mutation of a certain locus is the final step in tumorigenesis in a certain cell. If the chance of oncogenic mutation is 10-5 per allele of a gene , what is the chance that the cell (wild type for that gene) will become a cancer cell if the gene is (i) a proto-oncogene? (ii) a tumor suppressor gene?

4. Wild-type Rb protein can bind to protein E2F, sequestering it in the cytoplasm. When Rb protein is phosphorylated, it releases E2F, allowing E2F to enter the nucleus, where it can activate transcription of genes needed for entry into S phase.
(a) In cells where one copy of the Rb gene has been deleted and the other copy is normal, do you expect E2F to be sequestered in the cytoplasm or in the nucleus (assuming no phosphorylation of Rb)?
(b) In cells homozygous for deletion of the Rb gene, do you expect E2F to be sequestered in the cytoplasm or in the nucleus?
(c) Suppose a cell is heterozygous for deletion of the Rb gene and for deletion of the E2F gene. Do you expect E2F in this cell to be sequestered in the cytoplasm or in the nucleus?
(d) Suppose the cell in (d) undergoes additional mutations, so that it becomes homozygous for loss of the Rb gene and homozygous for loss of the E2F gene. Would you consider this cell to be in increased danger of progressing towards cancer? Explain.
(e) Suppose a different cell is heterozygous for a mutation in Rb such that the resulting protein remains bound to E2F even after phosphorylation. Would you consider this cell to be in increased danger of progressing towards cancer? Explain.

5. G1 phase cells in culture respond to treatment with the DNA-methylating agent MMS by delaying entry into S phase. A cell line with a mutation in gene xyz does not show this MMS-induced delay.
(a) Speculate on the consequences of this mutation to the genome of the cell.
(b) A popular hypothesis regarding gene xyz is that this gene acts as a checkpoint -- by delaying entry into S phase, the cell is given time to repair the damage caused by MMS. Suppose you had complete control over the phosphorylation state of Rb protein (i.e., you could turn phosphorylation of Rb on or off at will). Suggest an experiment to test the hypothesis regarding gene xyz. [Hint: you could use the mutant cell line and your control over Rb.]

6. Two potential food coloring agents, X and Y, were subjected to the Ames test for mutagenicity. Two his- strains of Salmonella were used as the test strains. Strain #1 had a missense mutation in the his gene, while strain #2 had a frameshift mutation in the his gene. The results, with or without liver extract in the medium, were as follows ('+' indicates growth and '-' indicates no growth of Salomonella colonies after treatment with the food coloring agent in medium lacking histidine):

Food coloring Strain #1 Strain #2
with liver extract no liver extract with liver extract no liver extract
X - - + -
Y - + - -

(a) Does either X or Y appear to be capable of causing mutations? If so, what kind of mutation (missense, or frameshift)?
(b) Which of these two compounds do you think might be worse for human consumption, and why? Would you feel comfortable certifying the other compound as safe for human consumption?

7. (a) A black cat produced the following litter of kittens: 2 calico and 1 black. Assuming that all kittens were fathered by the same cat, what was the probable sex of the black kitten? What was the father's probable color?
(b) A calico cat produced the following litter of kittens: 2 calico female, 1 black female, 1 orange male, and 2 black males. What was the probable color of the father (assuming there was just one father)?

8. This one is a modified exam question from 1998.

You have been working with two mice, Constance and Big Bertha, that show a high incidence of aborted fetuses in crosses with normal males. Constance had been X-irradiated when she was an embryo, and Big Bertha had been been exposed to a chemical mutagen when she was an embryo. The data you have collected on the aborted fetuses are:

Mother Sex of aborted fetuses Karyotype of aborted fetuses
Constance Female No Barr bodies
Big Bertha Female and male All X chromosomes form Barr bodies

(a) Explain why:
  1. all of Constance's daughters die
  2. all of Constances's sons survive
  3. all of Big Bertha's offspring die

[Note: This part is not asking about what defect the X-ray/mutagen treatment has caused; the question is only asking about what makes the offspring die or not die.]
(b) Explain how the X-ray treatment or mutagen treatment might have caused the phenotypes described above. In particular, what part of the X chromosome might be affected in each case, and how might that effect cause the observed phenotypes?
(c) A third female mouse (Chimney) showing high frequency of aborted fetuses was found subsequently. She too had been exposed to X-rays when she was an embryo. In her case, the aborted fetuses sometimes had a condensed, Barr body-like form of one chromosome 14 homolog. Briefly explain how this state might come about. Would you expect to see a male- or female-specific lethality in this case? Why, or why not?