Download Exercices Week 7

Exercises for BMC I
(Alberts, Fifth Edition, Chapter 8, pages 563-572)
27 October 2014
In each case, please justify briefly your answers! (single answer for MCQs)
1) Which method provides the ultimate proof that you identified the mutation that causes
a given phenotype in a forward genetic screen?
a) SNP mapping
b) Rescue experiment
c) Sequencing of the mutated allele
d) Haplotype mapping
e) Deficiency mapping
(Answer: b; see p. 8 of the presentation)
2) You cross a plant that has red flowers with a plant that has white flowers.
Whereas the F1 gives only plants with pink flowers, the F2 gives plants with a
range of colors from white to red, with several intermediate colors. What could
this be due to?
a) Dominant inheritance
b) Polygenic inheritance
c) Mitochondrial inheritance
d) Impact of the sex chromosomes
e) None of the above
(Answer: b; this is akin to the skin color example on p. 9. of the presentation,
with a bit of basic Mendelian genetics…).
3) Let us consider a hyperactive dominant mutant allele of a protein kinase, which leads
to fishes being smaller than normal. You conduct a forward genetic screen to identify
modifiers of this hyperactive mutant allele and identify a recessive suppressor that
restores normal size. For each of the following statements, pick “right” or “wrong”.
3a) The hyperactive dominant allele could be a receptor protein.
3c) The protein encoded by the gene mutated in the suppressor is a phosphatase.
3c) The protein encoded by the gene mutated in the suppressor likely promotes growth.
(Answers:
3a –right, this was seen in class last week with Achondroplasia, FGF3
receptor
3b – wrong, not necessarily, genetic interactions dot not reveal the molecular
nature of the components
3c – wrong, recessive mutations are usually reduction/loss-of-function alleles
–seen last week- and since less function of this component “pushes” the
system towards a larger size, the wild-type protein more likely limits growth.
4) You would like to study the function of DNA primase in C. elegans. Which forward
genetic or reverse genetic method(s) do you think would be well (or best) suited to do
so?
(Answers (several possible): DNA primase is an essential gene –something the
students should guess from the lecture on DNA replication earlier on in the class;
therefore, a straight knock-out will not work; possibilities include RNAi (reverse
genetics) –particularly well-suited for analyzing phenotypes in the early embryo; an
alternative would be a conditional mutant allele –e.g. temperature-sensitive (could be
obtained through forward genetics if one knows which phenotype to screen for, but
nowadays one would use CRISPR/Cas9 to generate a temperature-sensitive mutant,
using for instance the information from yeast as a guide –but they will see
CRISPR/Cas9 later in the semester, so that this answer is not expected at this stage,
but you can of course discuss this with them)
5) Which of the following does NOT apply to RNAi?
a) Involves the RISC complex.
b) Can lead to the cutting of target mRNA.
c) Can lead to a change in phenotype.
d) Can prevent splicing of target pre-mRNA.
e) Involves 21 nucleotide-long RNA species.
(Answer: d)
6) You would like to identify chemical compounds that promote specifically the killing of
cells overexpressing the oncogene c-Myc. How would you design such a screen?
(Answer: you would take a cell line, engineer it to overexpress c-Myc, probably under an
inducible promoter, and then select those chemical compounds that kills the cells
overexpressing c-Myc but not the control cells).