Page 104 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

Problems 263

23. In human DNA, 70% of cytosine residues that are The X-rays induce double-strand breaks in the
followed by guanine (so-called CpG dinucleotides, DNA. What kind of repair process are you witness-
where p indicates the phosphate in the phosphodiester ing in these harlequin chromosomes?
bond between these two nucleotides) are methylated c. At what point in the cell cycle did the repair pro-
to form 5-methylcytosine. As shown in the following cess described in part (b) take place? Explain.
figure, if 5-methylcytosine should undergo spontane- d. Bloom syndrome is an autosomal recessive disease
ous deamination, it becomes thymine. in humans characterized by short stature, distinc-
tive facial features, and an increased risk of cancer.
NH 2 O The preceding figure at the right actually shows
H C N Deamination H C NH cells of Bloom syndrome patients grown in BrdU
3
3
for the proper number of cell generations; almost
N O N O
H H all of these cells display harlequin chromosomes
5-methylcytosine Thymine even though the cells were not subjected to X-rays.
a. Methylated CpG dinucleotides are hotspots for What do you think is the function of the protein
point mutations in human DNA. Can you propose specified by the wild-type allele of the Bloom syn-
+
a hypothesis that explains why? drome gene (called BLM )?
b. Making the simplifying assumptions that human Section 7.4
DNA has an equal number of C–G and A–T base
pairs, and that the human DNA sequence is ran- 25. Albinism in animals is caused by recessive mutations in
dom, how frequently in the human genome would one of several autosomal genes required for synthesis of
you expect to find the base sequence CpG? melanin, a chemical precursor for many skin and eye pig-
ments. Albino animals are often confused with so-called
c. It turns out that, even after taking into account the leucistic animals that are white due to recessive mutations
actual GC content of human DNA (~42%), the fre- in a gene required in a different pathway, for example a
quency of CpG in human DNA is much lower than pathway for development of the cells that produce all skin
predicted by the calculation in part (b). Explain pigments. Suppose you have two white hummingbirds—
why this might be the case. a male and female—and they have mated. Assuming that
24. Bromodeoxyuridine (BrdU) is a synthetic nucleoside all relevant mutations are rare, autosomal, and recessive
that can be incorporated into newly synthesized DNA to wild-type alleles, what would you expect their progeny
in place of thymine (T). Researchers can add BrdU to to look like under the following conditions:
medium in which cells are growing, and then they can a. They are both albinos.
detect its presence in chromosomes by staining with
an antibody specific to BrdU. b. They are both leucistic.
a. The following figure at the left shows metaphase c. One is albino and the other is leucistic.
chromosomes isolated from somatic cells grown 26. a. In Figure 7.22b, what can you say about the
for some time in the presence of BrdU. Darker phenotype(s) of the progeny indicated by a +?
staining indicates more BrdU. For how many cell Explain.
generations have these cells been growing in the b. What about the phenotypes of the progeny indi-
presence of BrdU? cated by a − in the same figure? Explain.
27. Imagine that you caught a female albino mouse in
your kitchen and decided to keep it for a pet. A few
months later, while vacationing in Guam, you caught
a male albino mouse and decided to take it home for
some interesting genetic experiments. You wonder
whether the two mice are both albino due to muta-
tions in the same gene. What could you do to find out
the answer to this question? Assume that both muta-
Normal chromosomes Harlequin chromosomes tions are recessive.
© Maureen Sanz, Molloy College, Rockville Centre, NY 28. Plant breeders studying genes influencing leaf shape
b. So-called harlequin chromosomes (similar to those in the plant Arabidopsis thaliana identified six inde-
at the right of the figure) can be isolated from cells pendent recessive mutations that resulted in plants
grown in exactly the same way as those at the left, that had unusual leaves with serrated rather than
if the cells are exposed to X-rays a few hours be- smooth edges. The investigators started to perform
fore their chromosomes are prepared for analysis. complementation tests with these mutants, but some