Page 108 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

Problems 267

then self-fertilized to produce F 2 progeny as a. Show a simple linear biosynthetic pathway of the four
shown here. precursors and the end product, thymine. Indicate
which step is blocked by each of the five mutations.
Cross Parents F 1 F 2
b. What precursor would accumulate in the following
1 blue × white all purple 9 purple: 4 white: 3 blue double mutants: 9 and 10? 10 and 14?
2 white × white all purple 9 purple: 7 white 44. In 1952, an article in the British Medical Journal
3 red × blue all purple 9 purple: 3 red: 3 blue: 1 white reported interesting differences in the behavior of
4 purple × purple all purple 15 purple: 1 white
blood plasma obtained from several people who suf-
a. For each cross, explain the inheritance of flower fered from X-linked recessive hemophilia. When
color. mixed together, the cell-free blood plasma from cer-
b. For each cross, show a possible biochemical tain combinations of individuals could form clots in
the test tube. For example, the following table shows
pathway that could explain the data. whether clots could form (+) or not (−) in various
c. Which of these crosses is compatible with an un- combinations of plasma from four people with
derlying biochemical pathway involving only a hemophilia:
single step that is catalyzed by an enzyme with two
dissimilar subunits, both of which are required for 1 and 1 − 2 and 3 +
enzyme activity? 1 and 2 − 2 and 4 +
d. For each of the four crosses, what would you ex- 1 and 3 + 3 and 3 −
pect in the F 1 and F 2 generations if all relevant 1 and 4 + 3 and 4 −
genes were tightly linked? 2 and 2 − 4 and 4 −
42. The pathways for the biosynthesis of the amino acids
glutamine (Gln) and proline (Pro) involve one or more What do these data tell you about the inheritance of
common intermediates. Auxotrophic yeast mutants hemophilia in these individuals? Do these data allow
numbered 1–7 are isolated that require either gluta- you to exclude any models for the biochemical path-
mine or proline or both amino acids for their growth, way governing blood clotting?
as shown in the following table (+ means growth; − 45. Mutations in an autosomal gene in humans cause a
no growth). These mutants are also tested for their form of hemophilia called von Willebrand disease
ability to grow on the intermediates A–E. What is the (vWD). This gene specifies a blood plasma protein
order of these intermediates in the glutamine and pro- cleverly called von Willebrand factor (vWF). vWF
line pathways, and at which point in the pathways is stabilizes factor VIII, a blood plasma protein speci-
each mutant blocked? fied by the wild-type hemophilia A gene. Factor VIII
is needed to form blood clots. Thus, factor VIII is rap-
Gln + idly destroyed in the absence of vWF.
Mutant A B C D E Gln Pro Pro Which of the following might successfully be em-
1 + − − − + − + + ployed in the treatment of bleeding episodes in hemo-
2 − − − − − − + + philiac patients? Would the treatments work
3 − − + − − − − + immediately or only after some delay needed for
4 − − − − − + − + protein synthesis? Would the treatments have only a
5 − − + + − − − + short-term or a prolonged effect? Assume that all
6 + − − − − − + + mutations are null (that is, the mutations result in the
7 − + − − − + − + complete absence of the protein encoded by the gene)
and that the plasma is cell-free.
43. The following complementing E. coli mutants were a. transfusion of plasma from normal blood into a
tested for growth on four known precursors of vWD patient
thymine, A–D.
b. transfusion of plasma from a vWD patient into a
different vWD patient
Precursor/product
Mutant A B C D Thymine c. transfusion of plasma from a hemophilia A patient
into a vWD patient
9 + − + − +
10 − − + − + d. transfusion of plasma from normal blood into a he-
14 + + + − + mophilia A patient
18 + + + + + e. transfusion of plasma from a vWD patient into a
21 − − − − + hemophilia A patient